HK1088010A

HK1088010A - 1,3-diamino-2-hydroxypropane prodrug derivatives

Info

Publication number: HK1088010A
Application number: HK06108422.5A
Authority: HK
Inventors: Y．M．福毕安; J．N．福瑞斯克斯; B．杰顾琴斯卡
Original assignee: 艾伦药物公司; 法玛西和厄普约翰有限责任公司
Priority date: 2002-09-06
Filing date: 2003-09-08
Publication date: 2006-10-27

Description

1, 3-diamino-2-hydroxypropane prodrug derivatives

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from U.S. provisional application No.60/408,783, filed on 6/9/2002, which is incorporated herein by reference in its entirety.

Technical Field

The present invention relates to 1, 3-diamino-2-hydroxypropane prodrug derivatives and compounds useful for treating alzheimer's disease and related diseases. More particularly, the present invention relates to compounds that are capable of producing or producing in vitro or in vivo compounds that inhibit the beta-secretase enzyme that cleaves amyloid precursor protein to produce amyloid beta peptide (a β), an important component of amyloid plaques found in the brain of alzheimer's disease patients.

Background

Alzheimer's Disease (AD) is a progressive degenerative brain disease, primarily associated with aging. The clinical manifestations of AD are characterized by loss of memory, cognition, reasoning, judgment, and orientation. As the disease progresses, motor, sensory and linguistic abilities are also affected until there is a general decline in multi-cognitive function. These cognitive losses occur gradually, but usually lead to severe decline and eventual death in the range of four to twelve years.

Alzheimer's disease is characterized by two important pathological observations of the brain: neurofibrillary tangles and amyloid-beta (or neuroinflammatory) plaques, are composed primarily of aggregates of a peptide fragment known as a β. AD individuals exhibit characteristic beta-amyloid deposits in the brain (beta amyloid plaques) and in the brain blood vessels (beta amyloid angiopathy) as well as neurofibrillary tangles. Neurofibrillary tangles occur not only in alzheimer's disease but also in other dementia-inducing disorders. Autopsy typically finds a large number of these lesions in areas of the human brain that are important for memory and cognition.

These lesions are found in a smaller number and in a more limited anatomical distribution in the brains of most elderly people without clinical AD. Amyloidogenic plaques and amyloid angiopathy are also characteristic of the brain of individuals with Trisomy 21 (down's syndrome), hereditary cerebral hemorrhage with amyloidosis of the Dutch Type (HCHWA-D), and other neurodegenerative disorders. Beta-amyloid is a defining feature of AD and is now considered to be a causative precursor or factor in the development of disease. The deposition of a β in the brain regions responsible for cognitive activity is an important factor in the formation of AD. The β -amyloid plaques are composed primarily of the amyloid β peptide (a β, also sometimes referred to as β a 4). The A β peptide is derived from the proteolysis of Amyloid Precursor Protein (APP) and consists of amino acids 39-42. There are several proteases, called secretases, involved in the processing of APP.

APP is cleaved at the N-terminus of the A β peptide by β -secretase and at the C-terminus by one or more γ -secretases, which constitute the β -amyloidogenic pathway, i.e., the pathway by which A β is produced. Cleavage of APP by α -secretase produces α -sAPP, which is a secreted form of APP and does not result in the formation of β -amyloid plaques. This alternative route precludes the production of a β peptides. See, for example, U.S. Pat. Nos. 5,441,870, 5,721,130, and 5,942,400 for descriptions of proteolytically processed fragments of APP.

Aspartyl proteases have been identified as the enzymes responsible for processing of APP at the β -secretase cleavage site. Beta-secretases, including BACE, Asp, and Memapsin, have been disclosed using different nomenclature. See, for example, Sinha et al, 1999, Nature 402: 537- "Alternaria 554(p501) and PCT application publication WO 00/17369.

There is several lines of evidence that progressive brain deposition of β -amyloid peptide (a β) plays a key role in the pathogenesis of AD, being able to precede cognitive symptoms by years or decades. See, for example, Selkoe, 1991, Neuron 6: 487. the release of a β from neuronal cell cultures and the presence of a β in the cerebrospinal fluid (CSF) of both normal individuals and AD patients has been demonstrated. See, for example, Seubert et al, 1992, Nature 359: 325-327.

It has been proposed that a β peptide is accumulated as a result of processing of APP by β -secretase, and inhibition of the activity of this enzyme is desirable for the treatment of AD. In vivo processing of APP at the β -secretase cleavage site is considered to be the rate-limiting step in a β production and is therefore a therapeutic target for AD treatment. See, e.g., Sabbagh, m., et al, 1997, alz.dis.rev.3, 1-19.

BACE1 knockout mice are unable to produce A β and have a normal phenotype. When crossed with transgenic mice overexpressing APP, the progeny showed a reduction in the amount of A β in brain extracts compared to control animals (Luo et al, 2001 Nature Neuroscience 4: 231-. This evidence further supports the proposal that inhibition of β -secretase activity and reduction of a β in the brain provides a therapeutic approach for the treatment of AD and other β amyloid disorders.

Currently, there is no effective treatment to stop, prevent or reverse the progression of alzheimer's disease. Therefore, there is an urgent need for pharmaceutical agents capable of delaying the progression and/or preventing in the first place the alzheimer's disease.

The treatment and prevention of diseases characterized by amyloid beta deposits or plaques, such as AD, require effective β -secretase inhibitor compounds, compounds that inhibit β -secretase-mediated APP cleavage, effective a β production inhibitor compounds, and/or compounds that are effective in reducing amyloid deposits or plaques.

Disclosure of Invention

The present invention encompasses compounds of formulae (AA), (I) and (X) as shown below, pharmaceutical compositions containing these compounds, and methods of treating Alzheimer's disease using such compounds or compositions, and more particularly compounds that are capable of inhibiting the beta-secretase enzyme that cleaves amyloid precursor protein to produce A-beta peptide, which is an important component of the amyloid plaques found in the brain of Alzheimer's disease patients.

In one aspect, the invention provides a compound of formula AA:

and pharmaceutically acceptable salts thereof, wherein

R_NAnd R_NOne of them is hydrogen, and the other is hydrogen,

the other is-C (═ O) - (CRR')_0-6R₁₀₀、-C(＝O)-(CRR’)_1-6-O-R’₁₀₀、-C(＝O)-(CRR’)_1-6-S-R’₁₀₀、-C(＝O)-(CRR’)_1-6-C(＝O)-R₁₀₀、-C(＝O)-(CRR’)_1-6-SO₂-R₁₀₀、-C(＝O)-(CRR’)_1-6-NR₁₀₀-R’₁₀₀Or

Wherein

R₄Selected from: h; NH (NH)₂；-NH-(CH₂)_n6-R_4-1；-NHR₈；-NR₅₀C(O)R₅；C₁-C₄alkyl-NHC (O) R₅；-(CH₂)_0-4R₈；-O-C₁-C₄An alkanoyl group; OH; c₆-C₁₀Aryloxy optionally substituted with 1, 2 or 3 groups independently being halogen, C₁-C₄Alkyl, -CO₂H、-C(O)-C₁-C₄Alkoxy or C₁-C₄An alkoxy group; c₁-C₆An alkoxy group; aryl radical C₁-C₄An alkoxy group; -NR₅₀CO₂R₅₁；-C₁-C₄alkyl-NR₅₀CO₂R₅₁；-C≡N；-CF₃；-CF₂-CF₃；-C≡CH；-CH₂-CH＝CH₂；-(CH₂)_1-4-R_4-1；-(CH₂)_1-4-NH-R_4-1；-O-(CH₂)_n6-R_4-1；-S-(CH₂)_n6-R_4-1；-(CH₂)_0-4-NHC(O)-(CH₂)_0-6-R₅₂；-(CH₂)_0-4-R₅₃-(CH₂)_0-4-R₅₄；

Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-1is selected from-SO₂-(C₁-C₈Alkyl), -SO- (C)₁-C₈Alkyl), -S- (C)₁-C₈Alkyl), -S-CO- (C)₁-C₆Alkyl), -SO₂-NR_4-2R_4-3、-CO-C₁-C₂Alkyl, -CO-NR_4-3R_4-4；

R_4-2And R_4-3Independently is H, C₁-C₃Alkyl or C₃-C₆A cycloalkyl group;

R_4-4is alkyl, arylalkyl, alkanoyl or arylalkanoyl;

R_4-6is-H or C₁-C₆An alkyl group;

R₅selected from: c ₃-C₇A cycloalkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl group, C₆-C₁₀Aryl radical, C₃-C₇Cycloalkyl radical C₁-C₄Alkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl radical, C₆-C₁₀An aryloxy group;

heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; aryl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₆And R₇Independently selected from H, C₁-C₆Alkyl radical, C₂-C₆Alkanoyl, phenyl, -SO₂-C₁-C₄Alkyl, phenyl C₁-C₄An alkyl group;

R₈is selected from-SO₂-heteroaryl, -SO₂-aryl, -SO₂-heterocycloalkyl, -SO₂-C₁-C₁₀Alkyl, -C (O) NHR₉Heterocycloalkyl, -S-C₁-C₆Alkyl, -S-C₂-C₄Alkanoyl radical of which

R₉Is aryl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: aryl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, cyano, heteroaryl, -NR ₆R₇、-C(O)NR₆R₇、C₃-C₇Cycloalkyl or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, aryl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); an aryl group; a heterocycloalkyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the aryl, heterocycloalkyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group;

R₅₂is heterocycloalkyl, heteroaryl, aryl, cycloalkyl, -S (O)_0-2-C₁-C₆Alkyl, CO₂H、-C(O)NH₂-C (O) NH (alkyl), -C (O) N (alkyl), -CO ²-alkyl, -NHS (O)_0-2-C₁-C₆Alkyl, -N (alkyl) S (O)_0-2-C₁-C₆Alkyl, -S (O)_0-2-heteroaryl, -S (O)_0-2-aryl, -NH (arylalkyl), -N (alkyl) (arylalkyl), thioalkoxy or alkoxy, each of which is optionally substituted with 1, 2, 3, 4 or 5 groups, which are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO₂CN, alkoxycarbonyl or aminocarbonyl;

R₅₃is a bond, -O-, -C (O) -, -NH-, -N (alkyl) -, -NH-S (O)_0-2-, -N (alkyl) -S (O)_0-2-、-S(O)_0-2-NH-、-S(O)_0-2-N (alkyl) -, -NH-c(s) -or-N (alkyl) -c(s) -;

R₅₄is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO₂H、-CO₂Alkyl, -C (O) NH (alkyl), -C (O) N (alkyl), -C (O) NH₂、C₁-C₈Alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH₂NH (alkyl), N (alkyl) or-C₁-C₆alkyl-CO₂-C₁-C₆Alkyl, each of which is optionally substituted with 1, 2, 3, 4 or 5 groups which are independently alkyl, alkoxy, CO₂H、-CO₂-alkyl, thioAlkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, NO₂CN, alkoxycarbonyl or aminocarbonyl;

x is selected from: -C₁-C₆Alkylene, optionally substituted with 1, 2 or 3 methyl groups; and-NR _4-6-, or

R₄And R_4-6Combined to form- (CH)₂)_n10-, wherein

n₁₀Is 1, 2, 3 or 4;

z is selected from the group consisting of a bond, SO₂SO, S and C (O);

y is selected from: h; c₁-C₄A haloalkyl group; c₅-C₆A heterocycloalkyl group; c₆-C₁₀An aryl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl and halogen; an alkoxy group; aryl, optionally substituted by halogen, alkyl, alkoxy, CN or NO₂Substitution; arylalkyl, optionally substituted by halogen, alkyl, alkoxy, CN or NO₂Substitution; wherein

Y₁And Y₂Are identical or different and are H; c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C₁-C₄Alkoxy radical, C₃-C₈Cycloalkyl and OH;

C₂-C₆an alkenyl group; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; phenyl radical C₁-C₄An alkyl group; or C₃-C₈Cycloalkyl radical C₁-C₄Alkyl, or

Y₁、Y₂And the nitrogen to which they are attached form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1, 2, 3 or 4 groups, which are independently C ₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl or halogen;

R₁is- (CH)₂)_1-2-S(O)_0-2-(C₁-C₆Alkyl) or

C₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halo, OH, ═ O, -SH, -C ≡ N, -CF₃、-C₁-C₃Alkoxy, amino, mono-or dialkylamino, -n (R) c (O) R' -, -OC (═ O) -amino and-OC (═ O) -mono-or dialkylamino, or

C₂-C₆Alkenyl or C₂-C₆Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino and mono-or dialkylamino, or

Aryl, heteroaryl, heterocyclyl, -C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR' or-N (R) SO₂R′，-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

-C₁-C₆Alkoxy optionally substituted with 1, 2 or 3 groups which are independently halogen, or

C₃-C₇Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF ₃、C₁-C₃Alkoxy, amino, -C₁-C₆Alkyl and mono-or dialkylamino, or

C₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, mono-or dialkylamino and-C₁-C₃Alkyl, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and is

Heterocyclyl is optionally further substituted by oxo;

r and R' are independently hydrogen or C₁-C₁₀An alkyl group;

R₂selected from: h; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents independently selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy and-NR_1-aR_1-bWherein R is_1-aAnd R_1-bis-H or C₁-C₆An alkyl group; - (CH)₂)_0-4-an aryl group; - (CH)₂)_0-4-a heteroaryl group; c₂-C₆An alkenyl group; c₂-C₆An alkynyl group; -CONR_N-2R_N-3；-SO₂NR_N-2R_N-3；-CO₂H; and-CO₂-(C₁-C₄Alkyl groups);

R₃selected from: h; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents independently selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy and-NR_1-aR_1-b；-(CH₂)_0-4-an aryl group; - (CH)₂)_0-4-a heteroaryl group; c₂-C₆An alkenyl group; c₂-C₆An alkynyl group; -CO-NR_N-2R_N-3；-SO_2-NR_N-2R_N-3；-CO₂H; and-CO-O- (C) ₁-C₄Alkyl) or

R₂、R₃And the carbons to which they are attached form a carbocyclic ring of three to seven carbon atoms in which one carbon atom is optionally selected from-O-, -S-, -SO₂-or-NR_N-2-a group substitution;

R_Cselected from: c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_0-2(C₁-C₆Alkyl), -SH, -NR₂₃₅C＝ONR₂₃₅R₂₄₀、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-an aryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - (CR)₂₄₅R₂₅₀)_0-4-aryl-heteroaryl; - (CR)₂₄₅R₂₅₀)_0-4-aryl-heterocycloalkyl; - (CR)₂₄₅R₂₅₀)_0-4-aryl; - (CR)₂₄₅R₂₅₀)_0-4-heteroaryl-aryl; - (CR)₂₄₅R₂₅₀)_0-4-heteroaryl-heterocycloalkyl; - (CR)₂₄₅R₂₅₀)_0-4-heteroaryl; - (CR)₂₄₅R₂₅₀)_0-4-heterocycloalkyl-heteroaryl; - (CR)₂₄₅R₂₅₀)_0-4-heterocycloalkyl; - (CR)₂₄₅R₂₅₀)_0-4-heterocycloalkyl-aryl; - [ C (R)₂₅₅)(R₂₆₀)]_1-3-CO-N-(R₂₅₅)₂(ii) a -CH (aryl)₂(ii) a -CH (heteroaryl)₂(ii) a -CH (heterocycloalkyl)₂(ii) a -CH (aryl) (heteroaryl); a cyclopentyl, cyclohexyl or cycloheptyl ring fused to an aryl, heteroaryl or heterocycloalkyl group, wherein one carbon of the cyclopentyl, cyclohexyl or cycloheptyl group is optionally replaced by NH, NR₂₁₅O or S (═ O)_0-2And wherein the cyclopentyl, cyclohexyl, or cycloheptyl groups can optionally be substituted with 1 or 2 groups which are independently R ₂₀₅Or ═ O; -CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); c₂-C₁₀Alkenyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₁₀Alkynyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (CH)₂)_0-1-CH((CH₂)_0-6-OH)-(CH₂)_0-1-an aryl group; - (CH)₂)_0-1-CHR_C-6-(CH₂)_0-1-a heteroaryl group; -CH (-aryl or-heteroaryl) -CO-O (C)₁-C₄Alkyl groups); -CH (-CH)₂-OH) -CH (OH) -phenyl-NO₂；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; -CH₂-NH-CH₂-CH(-O-CH₂-CH₃)₂(ii) a -H; and- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R₂₀₀Substitution;

each heteroaryl group optionally substituted with 1, 2, 3 or 4R₂₀₀Substitution;

each heterocycloalkyl group is optionally substituted with 1, 2, 3 or 4R₂₁₀Substitution;

R₂₀₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO₂(ii) a Halogen; -CO₂H；C≡N；-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl); - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl groups); - (CH)₂)_0-4-CO-(C₃-C₇Cycloalkyl groups); - (CH)₂)_0-4-CO-aryl; - (CH)₂)_0-4-CO-heteroaryl; - (CH)₂)_0-4-CO-heterocycloalkyl; - (CH)₂)_0-4-CO₂R₂₁₅；-(CH₂)_0-4-SO₂-NR₂₂₀R₂₂₅；-(CH₂)_0-4-SO-(C₁-C₈Alkyl groups); - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-SO₂-(C₃-C₇Cycloalkyl groups); - (CH)₂)_0-4-N (H or R)₂₁₅)-CO₂R₂₁₅；-(CH₂)_0-4-N (H or R)₂₁₅)-CO-N(R₂₁₅)₂；-(CH₂)_0-4-N-CS-N(R₂₁₅)₂；-(CH₂)_0-4-N (-H or R)₂₁₅)-CO-R₂₂₀；-(CH₂)_0-4-NR₂₂₀R₂₂₅；-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl groups); - (CH)₂)_0-4-O-P(O)-(OR₂₄₀)₂；-(CH₂)_0-4-O-CO-N(R₂₁₅)₂；-(CH₂)_0-4-O-CS-N(R₂₁₅)₂；-(CH₂)_0-4-O-(R₂₁₅)₂；-(CH₂)_0-4-O-(R₂₁₅)₂-COOH；-(CH₂)_0-4-S-(R₂₁₅)₂；-(CH₂)_0-4-O- (C optionally substituted by 1, 2, 3 or 5-F)₁-C₆Alkyl groups); c₃-C₇A cycloalkyl group; c₂-C₆Alkenyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; c₂-C₆Alkynyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; - (CH)₂)_0-4-N (H or R)₂₁₅)-SO₂-R₂₂₀(ii) a And- (CH)₂)_0-4-C₃-C₇A cycloalkyl group;

wherein each aryl group is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R ₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group;

wherein each heterocycloalkyl group is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₁₀；

Wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group;

R₂₀₅independently at each occurrence is selected from C₁-C₆Alkyl, halogen, -OH, -O-phenyl, -SH, -C ≡ N, -CF₃、C₁-C₆Alkoxy, NH₂、NH(C₁-C₆Alkyl) and N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R₂₁₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkenyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkynyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; -NR₂₂₀R₂₂₅；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); and ═ O; wherein

R₂₁₅Independently at each occurrence is selected from C₁-C₆Alkyl, - (CH)₂)_0-2- (aryl), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which aryl is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R ₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence is selected from-H, -C₁-C₆Alkyl, hydroxy C₁-C₆Alkyl, amino C₁-C₆Alkyl, halo C₁-C₆Alkyl, -C₃-C₇Cycloalkyl, - (C)₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), - (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl), -C₂-C₆Alkenyl, -C₂-C₆Alkynyl, -C having a double bond and a triple bond₁-C₆Alkyl chains, -aryl, -heteroaryl and-heterocycloalkyl, wherein the aryl group is present at each occurrenceOptionally present by 1, 2 or 3R₂₇₀Substituted by groups; wherein

R₂₇₀Independently at each occurrence is R₂₀₅；C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkenyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkynyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; NR (nitrogen to noise ratio)₂₃₅R₂₄₀；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); and ═ O, where heterocycloalkyl is optionally substituted at each occurrence with 1, 2, or 3R₂₀₅Substituted by groups; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₀₅Substituted by groups;

R₂₃₅And R₂₄₀Independently at each occurrence is H or C₁-C₆An alkyl group;

R₂₄₅and R₂₅₀Independently at each occurrence selected from H, C₁-C₄Alkyl radical, C₁-C₄Hydroxyalkyl radical, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, - (CH)₂)_0-4-C₃-C₇Cycloalkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, aryl C₁-C₄Alkyl, heteroaryl C₁-C₄Alkyl and phenyl, or

R₂₄₅And R₂₅₀Together with the carbon to which they are attached form a carbocyclic ring of 3, 4, 5, 6 or 7 carbon atoms, optionally with one of the carbon atoms replaced by a heteroatom selected from-O-, -S-, -SO₂-and-NR₂₂₀-；

R₂₅₅And R₂₆₀Independently at each occurrence is selected from: h; c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkenyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkynyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (CH)₂)_1-2-S(O)_0-2-(C₁-C₆Alkyl groups); - (CH)₂)_0-4-C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (C)₁-C₄Alkyl) -aryl; - (C)₁-C₄Alkyl) -heteroaryl; - (C)₁-C₄Alkyl) -heterocycloalkyl; -an aryl group; -a heteroaryl group; -a heterocycloalkyl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-an aryl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-a heteroaryl group; and- (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-a heterocycloalkyl group,

wherein

R₂₆₅Independently at each occurrence is-O-, -S-or-N (C)₁-C₆Alkyl) -;

each aryl or phenyl group is optionally substituted with 1, 2 or 3 groups which are independently R ₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group;

R₁₀₀and R'₁₀₀Independently represents aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroarylaryl-W-heterocyclyl, -heteroaryl-W-aryl, heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, -CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-aryl, -CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-heterocyclyl or-CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-heteroaryl, wherein the cyclic moiety of each group is optionally substituted with 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl and (C)₂-C₁₀) Alkynyl, or

R₁₀₀Is C₁-C₁₀Alkyl, optionally substituted by 1, 2 or 3R₁₁₅Is substituted by radicals, or

R₁₀₀Is- (C)₁-C₆Alkyl) -O- (C₁-C₆Alkyl) or- (C)₁-C₆Alkyl) -S- (C₁-C₆Alkyl) each optionally substituted by 1, 2 or 3R₁₁₅Is substituted by radicals, or

R₁₀₀Is C₃-C₈Cycloalkyl optionally substituted by 1, 2 or 3R ₁₁₅Substituted by groups;

w is- (CH)₂)_0-4-、-O-、-S(O)_0-2-、-N(R₁₃₅) -, -CR (OH) -or-C (O) -;

R₁₀₂and R₁₀₂' is independently hydrogen, or C₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups which are independently halogen, aryl or-R₁₁₀；

R₁₀₅And R'₁₀₅Independently represent-H, -R₁₁₀-R₁₂₀、C₃-C₇Cycloalkyl, - (C)₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), - (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl group), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl or C having one double and one triple bond₁-C₆Alkyl chains, or

C₁-C₆Alkyl, optionally substituted by-OH or-NH₂Is substituted, or

C₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, or

R₁₀₅And R'₁₀₅Together with the atoms to which they are attached form a 3-to 7-membered carbocyclic ring in which one atom is optionally selected from-O-, -S (O)_0-2-、-N(R₁₃₅) -said ring being optionally substituted with 1, 2 or 3 groups independently selected from R₁₄₀A group;

R₁₁₅independently at each occurrence is halogen, -OH, -CO₂R₁₀₂、-C₁-C₆Thioalkoxy, -CO₂-phenyl, -NR₁₀₅R′₁₃₅、-SO₂-(C₁-C₈Alkyl), -C (═ O) R₁₈₀、R₁₈₀、-CONR₁₀₅R′₁₀₅、-SO₂NR₁₀₅R′₁₀₅、-NH-CO-(C₁-C₆Alkyl), -NH-C (═ O) -OH, -NH-C (═ O) -OR, -NH-C (═ O) -O-phenyl, -O-C (═ O) - (C)₁-C₆Alkyl), -O-C (═ O) -amino, -O-C (═ O) -mono-or dialkylamino, -O-C (═ O) -phenyl, -O- (C) -phenyl₁-C₆Alkyl) -CO₂H、-NH-SO₂-(C₁-C₆Alkyl group), C ₁-C₆Alkoxy or C₁-C₆A haloalkoxy group;

R₁₃₅is C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (aryl), - (CH)₂)_0-2- (heteroaryl) or- (CH)₂)_0-2- (heterocyclyl);

R₁₄₀is heterocyclyl, optionally substituted with 1, 2, 3 or 4 groups independently selected from C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C)₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl and ═ O;

R₁₄₅is C₁-C₆Alkyl or CF₃；

R₁₅₀Is hydrogen, C₃-C₇Cycloalkyl, - (C)₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C having one double bond and one triple bond₁-C₆Alkyl, -R₁₁₀、-R₁₂₀Or

C₁-C₆Alkyl optionally substituted with 1, 2, 3 or 4 groups independently selected from-OH, -NH₂、C₁-C₃Alkoxy radical, R₁₁₀And halogen;

R₁₅₀is' a C₃-C₇Cycloalkyl, - (C)₁-C₃Alkyl group) - (C₃-C₇Cycloalkyl), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C having one double bond and one triple bond₁-C₆Alkyl, -R₁₁₀、-R₁₂₀Or

R₁₅₅is C₃-C₇Cycloalkyl, - (C) ₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C having one double bond and one triple bond₁-C₆Alkyl, -R₁₁₀、-R₁₂₀Or

C₁-C₆Alkyl optionally substituted with 1, 2, 3 or 4 groups independently selected from-OH, -NH₂、C₁-C₃Alkoxy and halogen;

R₁₈₀selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S, S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3 or 4 groups selected from C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C)₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C¹-C⁶Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆Alkyl) amino (C)¹-C⁶) Alkyl and ═ O;

R₁₁₀is aryl, optionally substituted by 1 or 2R₁₂₅Substituted by groups;

R₁₂₅independently at each occurrence is halogen, amino, mono-or dialkylamino, -OH, -C.ident.N, -SO₂-NH₂、-SO₂-NH-C₁-C₆Alkyl, -SO₂-N(C₁-C₆Alkyl radical)₂、-SO²-(C¹-C⁴Alkyl), -CO-NH₂、-CO-NH-C₁-C₆Alkyl or-CO-N (C)₁-C₆Alkyl radical)²Or is or

C₁-C₆Alkyl radical, C₂-C₆Alkenyl or C₂-C₆Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from C ₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy, amino and mono-and dialkylamino, or

C₁-C₆Alkoxy optionally substituted with 1, 2 or 3 halo;

R₁₂₀is heteroaryl, optionally substituted by 1 or 2R₁₂₅Substituted by groups;

R₁₃₀is heterocyclyl, optionally substituted by 1 or 2R₁₂₅And (4) substituting the group.

The present invention also provides compounds of formula I:

and pharmaceutically acceptable salts thereof, wherein R₁、R₂、R₃And R_CIs as defined in formula (AA), and

R_Nis-C (═ C)O)-(CRR′)_0-6R₁₀₀、-C(＝O)-(CRR′)_1-6-O-R′₁₀₀、-C(＝O)-(CRR′)_1-6-S-R′₁₀₀、-C(＝O)-(CRR′)_1-6-C(＝O)-R₁₀₀、-C(＝O)-(CRR′)_1-6-SO₂-R₁₀₀、-C(＝O)-(CRR′)_1-6-NR₁₀₀-R′₁₀₀Or is or

R_NIs that

Wherein

R₄Selected from: h; NH (NH)₂；-NH-(CH₂)_n6-R_4-1；-NHR₈；-NR₅₀C(O)R₅；C₁-C⁴alkyl-NHC (O) R₅；-(CH₂)_0-4R₈；-O-C₁-C₄An alkanoyl group; OH; c₆-C₁₀Aryloxy optionally substituted with 1, 2 or 3 groups independently being halogen, C₁-C₄Alkyl, -CO²H、-C(O)-C₁-C₄Alkoxy or C₁-C₄An alkoxy group; c₁-C₆An alkoxy group; aryl radical C₁-C₄An alkoxy group; -NR₅₀CO₂R₅₁；-C₁-C₄alkyl-NR₅₀CO₂R₅₁；-C≡N；-CF₃；-CF₂-CF₃；-C≡CH；-CH₂-CH＝CH₂；-(CH₂)_1-4-R_4-1；-(CH₂)_1-4-NH-R_4-1；-O-(CH₂)_n6-R_4-1；-S-(CH₂)_n6-R_4-1；-(CH₂)_0-4-NHC(O)-(CH₂)_0-6-R₅₂；-(CH₂)_0-4-R₅₃-(CH₂)_0-4-R₅₄；

Wherein

n₆Is 0, 12, or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, arylalkyl, alkanoyl or arylalkanoyl;

R_4-6is-H or C₁-C₆An alkyl group;

R₅selected from: c₃-C₇A cycloalkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C ₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl group, C₆-C₁₀Aryl radical, C₃-C₇Cycloalkyl radical C₁-C₄Alkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl radical, C₆-C₁₀An aryloxy group; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄Alkanoyl radical(ii) a Aryl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₉Is aryl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: aryl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, cyano, heteroaryl, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇Cycloalkyl or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, aryl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); an aryl group; a heterocycloalkyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the aryl, heterocycloalkyl, C3-C8 cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group;

R₅₂is heterocycloalkyl, heteroaryl, aryl, cycloalkyl, -S (O)_0-2-C₁-C₆Alkyl, CO₂H、-C(O)NH₂-C (O) NH (alkyl), -C (O) N (alkyl), -CO₂-alkyl, -NHS (O)_0-2-C₁-C₆Alkyl, -N (alkyl) S (O)_0-2-C₁-C₆Alkyl, -S (O)_0-2-heteroaryl, -S (O)_0-2-aryl, -NH (arylalkyl), -N (alkyl) (arylalkyl), thioalkoxy or alkoxy, each of which is optionally substituted with 1, 2, 3, 4 or 5 groups, which are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO ₂CN, alkoxycarbonyl or aminocarbonyl;

R₅₃is connected withA bond, -O-, -C (O) -, -NH-, -N (alkyl) -, -NH-S (O)_0-2-, -N (alkyl) -S (O)_0-2-、-S(O)_0-2-NH-、-S(O)_0-2-N (alkyl) -, -NH-c(s) -or-N (alkyl) -c(s) -;

R₅₄is heteroaryl, aryl, arylalkyl, heterocycloalkyl, CO₂H、-CO₂Alkyl, -C (O) NH (alkyl), -C (O) N (alkyl), -C (O) NH₂、C₁-C₈Alkyl, OH, aryloxy, alkoxy, arylalkoxy, NH₂NH (alkyl), N (alkyl) or-C₁-C₆alkyl-CO₂-C₁-C₆Alkyl, each of which is optionally substituted with 1, 2, 3, 4 or 5 groups which are independently alkyl, alkoxy, CO₂H、-CO₂Alkyl, thioalkoxy, halogen, haloalkyl, haloalkoxy, hydroxyalkyl, alkanoyl, NO₂CN, alkoxycarbonyl or aminocarbonyl;

x is selected from: -C₁-C₆Alkylene, optionally substituted with 1, 2 or 3 methyl groups; and-NR_4-6-, or

R₄And R_4-6Combined to form- (CH)₂)_n10-, wherein

n₁₀Is 1, 2, 3 or 4;

z is selected from the group consisting of a bond, SO₂SO, S and C (O);

y is selected from: h; c₁-C₄A haloalkyl group; c₅-C₆A heterocycloalkyl group; c₆-C₁₀An aryl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c ₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl and halogen; an alkoxy group; aromatic hydrocarbonOptionally substituted by halogen, alkyl, alkoxy, CN or NO²Substitution; arylalkyl, optionally substituted by halogen, alkyl, alkoxy, CN or NO₂Substitution; wherein

Y₁And Y₂Are identical or different and are H; c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C₁-C₄Alkoxy radical, C₃-C₈Cycloalkyl and OH; c₂-C₆An alkenyl group; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; phenyl radical C₁-C₄An alkyl group; or C₃-C₈Cycloalkyl radical C₁-C₄Alkyl, or

Y₁、Y₂And the nitrogen to which they are attached form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1, 2, 3 or 4 groups, which are independently C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl or halogen;

R₁₀₀and R'₁₀₀Independently represents aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, -CH [ (CH) ₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-aryl, -CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-heterocyclyl or-CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-heteroaryl, wherein the cyclic moiety of each group is optionally substituted with 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)₀-₄-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl and (C)₂-C₁₀) Alkynyl, or

R₁₀₀Is C₃-C₈Cycloalkyl optionally substituted by 1, 2 or 3R₁₁₅Substituted by groups;

R₁₀₅And R'₁₀₅Independently represent-H, -R₁₁₀、-R₁₂₀、C₃-C₇Cycloalkyl, - (C)₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), - (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl group), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl or C having one double and one triple bond₁-C₆Alkyl chains, or

C₁-C₆Alkyl, optionally substituted by-OH or-NH₂Is substituted, or

R₁₁₅independently at each occurrence is halogen, -OH, -CO₂R₁₀₂、-C₁-C₆Thioalkoxy, -CO₂-phenyl, -NR₁₀₅R′₁₃₅、-SO₂-(C₁-C₈Alkyl), -C (═ O) R₁₈₀、R₁₈₀、-CONR₁₀₅R′₁₀₅、-SO₂NR₁₀₅R′₁₀₅、-NH-CO-(C₁-C₆Alkyl), -NH-C (═ O) -OH, -NH-C (═ O) -OR, -NH-C (═ O) -O-phenyl, -O-C (═ O) - (C)₁-C₆Alkyl), -O-C (═ O) -amino, -O-C (═ O) -mono-or dialkylamino, -O-C (═ O) -phenyl, -O- (C) -phenyl₁-C₆Alkyl) -CO₂H、-NH-SO₂-(C₁-C₆Alkyl group), C₁-C₆Alkoxy or C₁-C₆A haloalkoxy group;

R₁₃₅is C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₃-C₇Cycloalkyl, - (CH)₂)₀-₂- (aryl), - (CH)₂)_0-2- (heteroaryl) or- (CH)₂)_0-2- (heterocyclyl);

R₁₄₅is C₁-C₆Alkyl or CF ₃；

R₁₅₅is C₃-C₇Cycloalkyl, - (C)₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C having one double bond and one triple bond₁-C₆Alkyl, -R₁₁₀、-R₁₂₀Or

R₁₈₀selected from the group consisting of morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinyl, homothiomorpholinyl S-oxide, homothiomorpholinyl S, S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted with 1, 2, 3 or 4 groups selected from C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C) ₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆Alkyl) amino (C)₁-C₆) Alkyl and ═ O;

R₁₂₅independently at each occurrence is halogen, amino, mono-or dialkylamino, -OH, -C.ident.N, -SO₂-NH₂、-SO₂-NH-C₁-C₆Alkyl, -SO₂-N(C₁-C₆Alkyl radical)₂、-SO₂-(C₁-C₄Alkyl), -CO-NH₂、-CO-NH-C₁-C₆Alkyl or-CO-N (C)₁-C₆Alkyl radical)₂Or is or

C₁-C₆Alkyl radical, C₂-C₆Alkenyl or C₂-C₆Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy, amino and mono-and dialkylamino, or

C₁-C₆Alkoxy optionally substituted with 1, 2 or 3 halo;

The present invention also provides compounds of formula X:

and pharmaceutically acceptable salts thereof, wherein R₁、R₂、R₃、R_NAnd R_CIs as defined for formula (I).

The invention also provides a process for producing a compound of formula (Y) from a compound of formula (AA), (I) or (X):

wherein R is₁、R₂、R₃、R_NAnd R_CIs as defined for formula (I). The formation of the compound of formula (Y) from the compound of formula (AA), (I) or (X) may occur in vivo or in vitro. The compounds of formula Y are useful for the treatment and/or prevention of alzheimer's disease.

The invention also provides processes for converting a compound of formula AA, I or X to a compound of formula Y. The conversion and/or formation of the compound of formula Y comprises contacting the compound of formula I and/or X with an aqueous medium. Transformation may occur in vitro or in vivo.

The invention also provides a method of treating or preventing Alzheimer's disease, mild cognitive impairment, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, cerebral amyloid angiopathy, other degenerative dementias, dementia with mixed vascular and degenerative causes, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with corticobasal degeneration, Lewy body type (Lewy body type) Alzheimer's disease, comprising administering to a patient in need thereof a therapeutically effective amount of a compound or salt of formula AA, I or X.

Preferably, the patient is a human.

More preferably, the disease is alzheimer's disease.

More preferably, the disease is dementia.

The invention also provides a pharmaceutical composition comprising a compound or salt of formula AA, I or X and at least one pharmaceutically acceptable carrier, solvent, adjuvant or diluent.

The invention also provides the use of a compound or salt according to formula AA, I or X in the manufacture of a medicament.

The invention also provides the use of a compound or salt of formula (AA), formula (I) or formula (X) for the treatment or prophylaxis of Alzheimer's disease, mild cognitive impairment, Down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, cerebral amyloid angiopathy, other degenerative dementias, dementia of mixed vascular and degenerative origin, dementia associated with Parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with corticobasal degeneration or diffuse Lewy body type Alzheimer's disease.

The invention also provides compounds, pharmaceutical compositions, kits and methods for inhibiting beta-secretase-mediated Amyloid Precursor Protein (APP) cleavage. More specifically, the compounds, compositions and methods of the invention are effective in inhibiting the production of a- β peptide and in treating or preventing any human or animal disease or condition associated with pathological forms of a- β peptide.

The invention also provides processes for preparing the compounds of the invention and intermediates useful in these processes.

The compounds, compositions, and methods of the invention are useful for treating a human suffering from Alzheimer's Disease (AD), helping to prevent or delay the onset of AD, treating patients with Mild Cognitive Impairment (MCI), preventing or delaying the onset of AD that may experience a progression from MCI to AD, treating down's syndrome, treating hereditary cerebral hemorrhage with amyloidosis of the dutch-type, treating cerebral beta-amyloid angiopathy and preventing its potential consequences, such as single and recurrent cerebral lobe hemorrhage, treating other degenerative dementias, including dementia of mixed vascular and degenerative origin, treating dementia associated with parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration and diffuse lewy body AD, and treating frontotemporal dementia with parkinsonism (FTDP).

The compounds of formula Y have beta-secretase inhibitory activity. The inhibitory activity of the compounds of the invention is readily demonstrated, for example, using one or more assays described herein or known in the art.

Unless substituents of a particular structural formula are explicitly defined with respect to that structural formula, they are understood to have the definitions set forth in the prior structural formulas referenced with respect to that particular structural formula.

Detailed Description

As indicated above, the present invention provides compounds of formulae (AA), (I) and (X) which are useful in the treatment and prevention of Alzheimer's disease. These compounds can be regarded as prodrugs of the active compounds of the formula Y, since they produce the active compounds both in vivo and in vitro.

When contacted with water, compounds of formulae AA, I and X undergo R_NAcyl migration of the group as described in scheme 1. Migration associated with compounds of formula (I) is referred to herein as "N-acyl migration". Migration associated with compounds of formula (X) is referred to herein as "O-acyl migration".

Scheme 1 migration may occur in vitro or in vivo, and occurs when the compound is contacted with an aqueous medium, including water itself. The aqueous medium may be neutral, acidic or basic. Preferably, the pH of the medium is from about 2 to about 10, more preferably from about 3 to about 7. The amount of water required for migration is not critical. A catalytic amount of aqueous medium will be sufficient to cause migration. Aqueous buffer solutions as well as gastric juices are satisfactory media for migration to occur.

The rearrangement product of a compound of formula AA, formula I and/or formula X is a compound of formula (Y). Substituent R in Compound (Y)₁、R₂、R₃、R_NAnd R_CAre as defined above for the compounds of formula (I).

Reaction scheme 1

Preferred compounds of formula AA include those represented by formula AA-1, that is, compounds of formula AA wherein

R₁Is aryl, heteroaryl, heterocyclyl-C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR' or-N (R) SO₂R′，-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-orDialkylamino, -SO₂-(C₁-C₄) Alkyl, or

-C₁-C₆Alkoxy optionally substituted with 1, 2 or 3 groups independently selected from halogen, or

C₃-C₇Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, -C₁-C₆Alkyl and mono-or dialkylamino, or

C₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF ₃、C₁-C₃Alkoxy, amino, mono-or dialkylamino and-C₁-C₃Alkyl, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and the heterocyclyl is optionally further substituted by oxo.

Preferred compounds of the formula AA-1 also include those in which

R₁is-C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR' or-N (R) SO₂R′，-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -Mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF³、C₁-C₃Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and the heterocyclyl is optionally further substituted by oxo.

Preferred compounds of the formula AA-1 further include those wherein

R₁Is- (CH)₂) -aryl, - (CH)₂) -heteroaryl or- (CH)₂) -heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R、-N(R)COR′、-N(R)SO²R′、-C(＝O)-(C₁-C⁴) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₁-C₆Alkoxy optionally substituted with 1, 2 or 3 groups independently selected from halogen, or

Preferred compounds of the formula AA-1 also include those in which

R₁is-CH₂-phenyl or-CH₂-pyridyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, C₁-C₄Alkoxy, hydroxy, -NO₂And are and

C₁-C₄alkyl optionally substituted with 1, 2 or 3 substituents independently selected from halogen, OH, SH, NH₂、NH(C₁-C₆Alkyl), N- (C)₁-C₆Alkyl) (C₁-C⁶Alkyl), C.ident. N, CF₃。

Preferred compounds of the formula AA-1 further include those wherein

R₁is-CH₂-phenyl or-CH₂-pyridyl, wherein the phenyl or pyridyl ring is each optionally substituted with 1 or 2 groups independently selected from halogen, C₁-C₂Alkyl radical, C₁-C₂Alkoxy, hydroxy, -CF₃and-NO₂。

Preferred compounds of the formula AA-1 include those in which

R₁is-CH₂-phenyl, wherein the phenyl ring is optionally substituted with 2 groups independently selected from halogen, C ₁-C₂Alkyl radical, C₁-C₂Alkoxy, hydroxy and-NO₂。

Preferred compounds of formula AA-1 also include those wherein R₁Is benzyl or 3, 5-difluorobenzyl.

Preferred compounds of formula AA and AA-1 include those represented by formula AA-2, that is, compounds of formula AA or AA-1 wherein

R₂And R₃Independently selected from H or C₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy and-NR₁-aR_1-b。

Preferred compounds of formula AA-2 include those wherein

R_CSelected from: c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_n-2(C₁-C⁶Alkyl), -SH, -NR₂₃₅C＝ONR₂₃₅R₂₄₀、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-an aryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - [ C (R)₂₅₅)(R₂₆₀)]_1-3-CO-N-(R₂₅₅)₂(ii) a -CH (aryl)²(ii) a -CH (heteroaryl)₂(ii) a -CH (heterocycloalkyl)₂(ii) a -CH (aryl) (heteroaryl); -CO-NR₂₃₅R₂₄₀；-(CH₂)_0-1-CH((CH₂)_0-6-OH)-(CH₂)_0-1-an aryl group; - (CH)₂)_0-1-CHR_C-6-(CH²)_0-1-a heteroaryl group; -CH (-aryl or-heteroaryl) -CO-O (C)₁-C₄Alkyl groups); -CH (-CH)₂-OH) -CH (OH) -phenyl-NO²；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; -CH₂-NH-CH₂-CH(-O-CH₂-CH₃)₂(ii) a -H; and- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R ₂₀₀Substitution;

R₂₀₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO₂(ii) a Halogen; -CO₂H；C≡N；-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-CO₂R₂₁₅(ii) a And- (CH)₂)_0-4-O- (C optionally substituted by 1, 2, 3 or 5-F)₁-C₆Alkyl groups);

wherein each aryl group is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group;

R₂₁₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c ₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; -NR₂₂₀R₂₂₅；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl radical) (ii) a And ═ O; wherein

R₂₁₅Independently at each occurrence is selected from C₁-C₆Alkyl, - (CH)₂)_0-2- (aryl), C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which aryl is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence is selected from-H, -C₁-C₆Alkyl, hydroxy C₁-C₆Alkyl, amino C₁-C₆Alkyl, halo C₁-C₆Alkyl, -C₃-C₇Cycloalkyl, - (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl), -aryl, -heteroaryl and-heterocycloalkyl, wherein the aryl is optionally substituted at each occurrence with 1, 2 or 3R₂₇₀Each heteroaryl group optionally substituted with 1, 2, 3 or 4R₂₀₀Substituted by radicals, each heterocycloalkyl group optionally being substituted by 1, 2, 3 or 4R₂₁₀Substituted by groups; wherein

R₂₇₀Independently at each occurrence is R₂₀₅；C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c ₁-C₆A haloalkoxy group; NR (nitrogen to noise ratio)₂₃₅R₂₄₀；OH；C≡N；-CO-(C₁-C₄Alkyl groups); and ═ O, where heterocycloalkyl is optionally substituted at each occurrence with 1, 2, or 3R₂₀₅Substituted by groups; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₀₅Substituted by groups;

R₂₃₅and R₂₄₀At each occurrence is individuallyThe root of the earth is H or C₁-C₆An alkyl group;

R₂₄₅and R₂₅₀Independently at each occurrence selected from H, C₁-C₄Alkyl radical, C₁-C₄Hydroxyalkyl radical, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, or

R₂₄₅And R₂₅₀Together with the carbon to which they are attached form a carbocyclic ring of 3, 4, 5, 6 or 7 carbon atoms, wherein the carbocyclic ring is optionally substituted with 1 or 2 groups which are independently OH, methyl, Cl, F, OCH₃、CF₃、NO₂Or CN;

R₂₅₅and R₂₆₀Independently at each occurrence is selected from: h; c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (CH)₂)_0-4-C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (C)₁-C₄Alkyl) -aryl; - (C)₁-C₄Alkyl) -heteroaryl; - (C)₁-C₄Alkyl) -heterocycloalkyl; -an aryl group; -a heteroaryl group; -a heterocycloalkyl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-an aryl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-a heteroaryl group; and- (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-heterocycloalkyl, wherein

R₂₆₅Independently at each occurrence is-O-, -S-or-N (C)₁-C₆Alkyl) -;

each aryl or phenyl group is optionally substituted with 1, 2 or 3 groups which are independently R ₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group.

Preferred compounds of formula AA-2 include those wherein

R_CIs- (CR)₂₄₅R₂₅₀)_0-4-aryl or- (CR)₂₄₅R₂₅₀)_0-4Heteroaryl, wherein aryl and heteroaryl are optionally substituted by 1, 2 or 3R₂₀₀And (4) substituting the group.

Preferred compounds of formula AA-2 also include those wherein

R_CIs- (CR)₂₄₅R₂₅₀) -aryl or- (CR)₂₄₅R₂₅₀) Heteroaryl, wherein aryl and heteroaryl are optionally substituted by 1, 2 or 3R₂₀₀And (4) substituting the group.

Preferred compounds of formula AA-2 also include those wherein

R_CIs- (CH)₂) -aryl or- (CH)₂) Heteroaryl, wherein each aryl and heteroaryl is optionally substituted with 1, 2 or 3 groups selected from OH, -NO₂Halogen, -CO₂H、C≡N、-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl) and- (CH)₂)_0-4-SO₂-NR₂₂₀R₂₂₅。

Preferred compounds of formula AA-2 also include those wherein

R_CIs- (CH)₂) -aryl, wherein aryl is optionally substituted with 1, 2 or 3 groups selected from OH, -NO₂Halogen, -CO₂H and C ≡ N.

Preferred compounds of formula AA-2 also include those wherein

R_CIs- (CH)₂) -phenyl, wherein phenyl is optionally substituted with 1, 2 or 3 groups selected from OH, -NO₂Halogen, -CO₂H and C ≡ N.

Preferred compounds of formula AA-2 also include Wherein R is_CIs benzyl.

Other preferred compounds of formulas AA, AA-1 and AA-2 include compounds of formula AA-3, i.e., those represented by formulas AA, AA-1 or AA-2, wherein R is_NAnd R_NOne is hydrogen and the other is:

wherein

R₄Is NH₂、-NH-(CH₂)_n6-R_4-1、-NHR₈、-NR₅₀C(O)R₅or-NR₅₀CO₂R₅₁，

Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆An alkoxy group,more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl, or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₆And R₇Independently selected from H, C₁-C₆Alkyl radical, C₂-C₆Alkanoyl, phenyl, -SO₂-C₁-C₄Alkyl and phenyl C₁-C₄An alkyl group;

R₈selected from: -SO₂-heteroaryl, optionally substituted with 1 or 2 groups, which are independently C₁-C₄Alkyl or halogen;-SO₂-an aryl group; -SO₂-a heterocycloalkyl group; -C (O) NHR⁹(ii) a A heterocycloalkyl group; -S-C₂-C₄Alkanoyl radical of which

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group. Preferred compounds of formula AA-3 include those wherein R is_NAnd R_NOne of which is hydrogen and the other is

Wherein

X is C₁-C₄Alkylene, optionally substituted with 1, 2 or 3 methyl groups; or-NR_4-6-, or

R₄And R_4-6Combined to form- (CH)₂)_n10-, wherein

n₁₀Is 1, 2, 3 or 4;

z is selected from the group consisting of a bond, SO ₂SO, S and C (O);

y is selected from H; c₁-C₄A haloalkyl group; c₅-C₆Heterocycloalkyl containing at least one of N, O or S; a phenyl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl and halogen; an alkoxy group; phenyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; phenyl radical C₁-C₄Alkyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; wherein

C₂-C₆an alkenyl group; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; phenyl radical C₁-C₄An alkyl group; and C₃-C₈Cycloalkyl radical C₁-C₄An alkyl group; or

-N(Y₁)(Y₂) Form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1, 2, 3 or 4 groups independently C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl or halogen.

Preferred compounds of formula AA-3 include those wherein

X is C₁-C₄Alkylene, optionally substituted with 1, 2 or 3 methyl groups;

z is selected from SO₂SO, S and C (O);

Y₁And Y₂Are identical or different and are H; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C₁-C₄Alkoxy radical, C₃-C₈Cycloalkyl and OH; c₂-C₆An alkenyl group; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; phenyl radical C₁-C₄An alkyl group; or C₃-C₈Cycloalkyl radical C₁-C₄Alkyl, or

-N(Y₁)(Y₂) Form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1, 2, 3 or 4 groups independently C ₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl or halogen.

Preferred compounds of formula AA-3 include those wherein R is_NAnd R_NOne is hydrogen and the other is:

wherein

R₄Is NH₂、-NH-(CH₂)_n6-R_4-1、-NHR₈、-NR₅₀C(O)R₅or-NR₅₀CO₂R₅₁Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical,C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl, or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₈selected from: -SO₂-heteroaryl, optionally substituted with 1 or 2 groups, which are independently C₁-C₄Alkyl or halogen; -SO₂-an aryl group; -SO₂-a heterocycloalkyl group; -C (O) NHR₉(ii) a A heterocycloalkyl group; -S-C₂-C₄Alkanoyl radical of which

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group; and is

R₅₁Selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group; and Y is C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy.

Preferred compounds of formula AA-3 further include those wherein

R_CIs C₁-C₈Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_0-2(C₁-C₆Alkyl), -SH, -C ═ ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-a phenyl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - (CH)₂)_0-1-CH((CH₂)_0-4-OH)-(CH₂)_0-1-a phenyl group; - (CH)₂)_0-1-CHR_C-6-(CH₂)_0-1-a heteroaryl group; -CH (-CH)₂-OH) -CH (OH) -phenyl-NO₂；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; or- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R₂₀₀Substitution;

R₂₀₀independently at each occurrence is C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO₂(ii) a Halogen; -CO₂H；C≡N；-(CH²)^0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-CO₂R₂₁₅(ii) a Or- (CH)₂)_0-4-O- (C optionally substituted by 1, 2, 3 or 5-F)₁-C₆Alkyl groups);

R₂₀₅independently at each occurrence is C₁-C₆Alkyl, halogen, -OH, -O-phenyl, -SH, -C ≡ N, -CF₃、C₁-C₆Alkoxy, NH₂、NH(C₁-C₆Alkyl) or N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R₂₁₀independently at each occurrence is C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; -NR ₂₂₀R₂₂₅；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); and ═ O;

R₂₁₅independently at each occurrence is C₁-C₆Alkyl, - (CH)₂)_0-2- (phenyl), C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which the phenyl radical is not essential at each occurrenceIs substituted with 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence-H, -C₁-C₆Alkyl, hydroxy C₁-C₆Alkyl, halo C₁-C₆Alkyl, -C₃-C₇Cycloalkyl and- (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl groups);

R₂₄₅And R₂₅₀Together with the carbon to which they are attached form a carbocyclic ring of 3, 4, 5, 6 or 7 carbon atoms.

Preferred compounds of formula AA-3 include those wherein

R₁Is benzyl optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, C₁-C₄Alkoxy, hydroxy and C ₁-C₄Alkyl, optionally substituted by 1, 2 or 3 halogen, OH, SH, NH₂、NH(C₁-C₆Alkyl), N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl), C.ident. N, CF₃Substitution;

R₂and R₃Independently selected from H or C₁-C₄Alkyl optionally substituted with 1 substituent selected from the group consisting of halogen, -OH, and,-SH、-C≡N、-CF₃、C₁-C₃Alkoxy, NH²、NH(C₁-C₆Alkyl) and NH (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R_Cis C₁-C₈Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-SH、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-phenyl, optionally substituted by 1, 2 or 3R₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-a pyridyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyridazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrimidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a furyl group; - (CR)₂₄₅R₂₅₀)_0-3-an indolyl group; - (CR)₂₄₅R₂₅₀)_0-3-thienyl; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrazolyl group; - (CR)₂₄₅R₂₅₀)_0-3-a benzoxazolyl group; - (CR)₂₄₅R₂₅₀)_0-3Imidazolyl optionally substituted by 1, 2, 3 or 4R for each of the above heteroaryl groups₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-imidazolidinyl; - (CR)₂₄₅R₂₅₀)_0-3-a tetrahydrofuranyl group; - (CR)₂₄₅R₂₅₀)_0-3-a tetrahydropyranyl group; - (CR)₂₄₅R₂₅₀)_0-3-a piperazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a piperidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-indolyl, each of said heterocycloalkyl optionally substituted by 1, 2, 3 or 4R₂₁₀Substitution; - (CH) ₂)_0-1-CH((CH₂)_0-4-OH)-(CH₂)_0-1-a phenyl group; - (CH)₂)_0-1-CH(C₁-C₄Hydroxyalkyl) - (CH₂)_0-1-a pyridyl group;

R₂₀₀independently at each occurrence is C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO₂(ii) a Halogen; -CO₂H；C≡N；-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₈Alkyl groups); - (CH)₂)_0-4-CO₂R₂₁₅(ii) a And- (CH)₂)_0-4-O- (C optionally substituted by 1, 2, 3 or 5-F)₁-C₆Alkyl groups);

R₂₀₅independently at each occurrence is C₁-C₆Alkyl, halogen, -OH, -O-phenyl, -SH, -C ≡ N, -CF₃、C₁-C₆Alkoxy, NH₂、NH(C₁-C₆Alkyl) and N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R₂₁₀independently at each occurrence is C₁-C₆Alkyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; halogen; c₁-C₄An alkoxy group; c₁-C₄A haloalkoxy group; -NR₂₂₀R₂₂₅；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1 or 2R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); and ═ O;

R₂₁₅independently at each occurrence is C₁-C₆Alkyl, - (CH)₂)_0-2- (phenyl), C₃-C₆Cycloalkyl, - (CH)₂)_0-2- (pyridyl), - (CH)₂)_0-2- (pyrrolyl), - (CH)₂)_0-2- (imidazolyl), - (CH)₂)^0-2- (pyrimidinyl), - (CH)₂)_0-2- (pyrrolidinyl), - (CH)₂)_0-2- (imidazolidinyl), - (CH)₂)_0-2- (piperazinyl), - (CH)₂)_0-2- (piperidinyl) and- (CH)₂)_0-2- (morpholinyl) wherein phenyl is optionally substituted at each occurrence by 1 or 2 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein each heterocycloalkyl group is optionally substituted at each occurrence with 1 or 2R ₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence by 1 or 2R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence-H, -C₁-C₄Alkyl, hydroxy C₁-C₄Alkyl, halo C₁-C₄Alkyl, -C₃-C₆Cycloalkyl and- (C)₁-C₄Alkyl) -O- (C₁-C₂Alkyl groups);

R₂₄₅and R₂₅₀H, C independently at each occurrence₁-C₄Alkyl radical, C₁-C₄Hydroxyalkyl radical, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, or

R₂₄₅And R₂₅₀Together with the carbon to which they are attached form a carbocyclic ring of 3, 4, 5 or 6 carbon atoms.

Other preferred compounds of formula AA-3 include those wherein

X is-C₁-C₃Alkylene, optionally substituted with 1 or 2 methyl groups;

z is SO₂SO, S and C (O);

y is C₁-C₄A haloalkyl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 or 2 substituents, which may be the same or different, selected from halogen, hydroxy, C₁-C₄Alkoxy radical, C₁-C₄Thioalkoxy and C₁-C₄A haloalkoxy group; c₁-C₄An alkoxy group; phenyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; and benzyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; wherein

Y₁And Y₂Are identical or different and are H; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C ₁-C₂Alkoxy radical, C₃-C₆Cycloalkyl and OH;

C₂-C₆an alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; a benzyl group; and C₃-C₆Cycloalkyl radical C₁-C₂Alkyl, or

Preferred compounds of formula AA-3 also include those represented by formula AA-4, i.e., compounds of formula AA-3 wherein

X is-C₁-C₃Alkylene, optionally substituted with 1 methyl group;

z is SO₂SO, S or C (O);

y is OH; -N (Y)₁)(Y₂) (ii) a A phenyl group; a benzyl group; or C₁-C₁₀Alkyl, optionally substituted with 1 or 2 substituents, which may be the same or different, selected from halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy and CF₃(ii) a Wherein

Y₁And Y₂Are identical or different and are H; c₁-C₄Alkyl, optionally substituted with 1 or 2 substituents selected from halogen, methoxy, ethoxy, cyclopropyl and OH, or

-N(Y₁)(Y₂) Form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1 or 2 groups, which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy or halogen;

R₁is benzyl optionally substituted with 1, 2 or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, -CH²CF³Methoxymethyl, halogen, methoxy, ethoxy, n-propoxy, isopropoxy and OH;

R₂and R₃Independently is H or C₁-C₄An alkyl group;

R_Cis C₁-C₆Alkyl, optionally substituted by 1, 2 or 3 radicals R₂₀₅Substitution; a cyclopropyl group; a cyclopropyl methyl group; a cyclopentyl group; a cyclopentyl methyl group; a cyclohexyl group; a cyclohexylmethyl group; - (CR)₂₄₅R₂₅₀)_0-3-phenyl, optionally substituted by 1 or 2R₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-pyridyl optionally substituted by 1 or 2R₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-a piperazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolidinyl group; - (CR)₂₄₅R₂₅₀)_0-3Piperidinyl, each of said heterocycloalkyl optionally substituted by 1 or 2R₂₁₀Substitution;

R₂₀₀independently at each occurrence is selected from C₁-C₄Alkyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; OH; and halogen;

R₂₀₅independently at each occurrence is selected from C₁-C₄Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃And C₁-C₄An alkoxy group;

R₂₁₀independently at each occurrence is selected from C₁-C₄Alkyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; halogen; c₁-C₄An alkoxy group; OCF₃；NH₂；NH(C₁-C₆Alkyl groups); n (C) ₁-C₆Alkyl) (C₁-C₆Alkyl groups); OH; and-CO- (C)₁-C₄Alkyl groups);

R₂₄₅and R₂₅₀Independently at each occurrence selected from H, C₁-C₄Hydroxyalkyl radical, C₁-C₄Alkoxy radical, or

R₂₄₅And R₂₅₀Together with the carbon to which they are attached form a carbocyclic ring of 3, 5 or 6 carbon atoms.

Preferred compounds of the formulae AA, AA-1 and AA-2 include those of the formula AA-5, i.e., those represented by the formulae AA, AA-1 or AA-2, wherein

R_NAnd R_N'one is hydrogen and the other is-C (═ O) - (CRR')_0-6R₁₀₀(ii) a And is

R₁₀₀Represents aryl, heteroaryl OR heterocyclyl, wherein the ring part of each group is optionally substituted by 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Preferred compounds of formula AA-5 include those wherein

R_NAnd R_N' one is hydrogen and the other is-C (═ O) -R₁₀₀(ii) a And is

R₁₀₀Represents aryl OR heteroaryl, wherein the ring part of each group is optionally substituted by 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH) ₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)₀-₄-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、 -(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Preferred compounds of formula AA-5 also include those wherein

R_NAnd R_N' one is hydrogen and the other is-C (═ O) -aryl OR-C (═ O) -heteroaryl, wherein the ring portion of each group is optionally substituted with 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO²-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Other preferred compounds of formula AA-5 include those wherein

R_NAnd R_N' one is hydrogen and the other is-C (═ O) -arylor-C (═ O) -heteroaryl, wherein the ring portion of each group is optionally substituted with 1 or 2 groups independently selected from C₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)₀-₄-SO₂-N R₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl, - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₁₀) Alkynyl.

Other preferred compounds of formula AA-5 include those wherein

R_NAnd R_N' one is hydrogen and the other is-C (═ O) -phenyl, wherein the phenyl ring is optionally substituted with 1 or 2 groups independently selected from C ₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl, - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₀) Alkynyl.

Other preferred compounds of formula AA-5 also include those wherein

R_NAnd R_NOne is hydrogen and the other is:

wherein sub is hydrogen or C₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl, - (C)₂-C₁₀) Alkenyl, - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₀) Alkynyl.

Preferred stereochemistry of compounds of formula AA are as follows:

preferred compounds of formula I include those represented by formula I-1, that is, compounds of formula I wherein

R₁Is aryl, heteroaryl, heterocyclyl-C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C¹-C⁶Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR', or-N (R) SO₂R′、-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₁-C₆Alkoxy radicals, optionallyIs substituted with 1, 2 or 3 groups independently selected from halogen, or

C₃-C₇Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, -C ¹-C⁶Alkyl and mono-or dialkylamino, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C³Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and the heterocyclyl is optionally further substituted by oxo.

Preferred compounds of the formula I-1 also include those in which

R₁is-C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR', or-N (R) SO₂R′、-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₁-C₆An alkoxy group,optionally substituted with 1, 2 or 3 groups independently selected from halogen, or

Preferred compounds of the formula I-1 further include those in which

R₁Is- (CH)₂) -aryl, - (CH)₂) -heteroaryl or- (CH)₂) -heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR', or-N (R) SO₂R′、-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₁-C₆Alkoxy, optionally substituted by 1, 2 or 3 groupsThe substituent groups are independently selected from halogen, or

Preferred compounds of the formula I-1 also include those in which

C₁-C₄alkyl optionally substituted with 1, 2 or 3 substituents independently selected from halogen, OH, SH, NH₂、NH(C₁-C₆Alkyl), N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl), C.ident. N, CF₃。

Preferred compounds of the formula I-1 further include those in which

R₁is-CH₂-phenyl or-CH₂-pyridyl, wherein the phenyl or pyridyl ring is each optionally substituted with 1 or 2 groups independently selected from halogen, C ₁-C₂Alkyl radical, C₁-C₂Alkoxy, hydroxy, -CF₃and-NO₂。

Preferred compounds of formula I-1 include those wherein

R₁is-CH₂-phenyl, wherein the phenyl ring is optionally substituted with 2 groups independently selected from halogen, C₁-C₂Alkyl radical, C₁-C₂Alkoxy, hydroxy and-NO₂。

Preferred compounds of formula I-1 also include those wherein R₁Is benzyl or 3, 5-difluorobenzyl.

Preferred compounds of formula I and I-1 include those represented by formula I-2, that is, compounds of formula I or I-1 wherein

R₂And R₃Independently selected from H or C₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy and-NR_1-aR_1-b。

Preferred compounds of formula I-2 include those wherein

R_CSelected from: c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_0-2(C₁-C₆Alkyl), -SH, -NR₂₃₅C＝ONR₂₃₅R₂₄₀、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted by 1, 2 or 3 radicalsIs independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-an aryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - [ C (R)₂₅₅)(R₂₆₀)]_1-3-CO-N-(R₂₅₅)₂(ii) a -CH (aryl)²(ii) a -CH (heteroaryl)₂(ii) a -CH (heterocycloalkyl)₂(ii) a -CH (aryl) (heteroaryl); -CO-NR ₂₃₅R₂₄₀；-(CH₂)_0-1-CH((CH₂)_0-6-OH)-(CH₂)_0-1-an aryl group; - (CH)₂)_0-1-CHR_C-6-(CH₂)_0-1-a heteroaryl group; -CH (-aryl or-heteroaryl) -CO-O (C)₁-C₄Alkyl groups); -CH (-CH)₂-OH) -CH (OH) -phenyl-NO²；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; -CH₂-NH-CH₂-CH(-O-CH₂-CH₃)₂(ii) a -H; and- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R₂₀₀Substitution;

R₂₀₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO₂(ii) a Halogen; -CO₂H；C≡N；-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-CO₂R₂₁₅(ii) a And- (CH)₂)_0-4-O- (optionally with 1, 2)C substituted by 3 or 5-F₁-C₆Alkyl groups);

R₂₀₅independently at each occurrence is selected from C ₁-C₆Alkyl, halogen, -OH, -O-phenyl, -SH, -C ≡ N, -CF₃、C₁-C₆Alkoxy, NH₂、NH(C₁-C₆Alkyl) and N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R₂₁₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; -NR₂₂₀R₂₂₅；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); and ═ O;

R₂₁₅independently at each occurrence is selected from C₁-C₆Alkyl, - (CH)₂)_0-2- (aryl radicals))、C₃-C₇Cycloalkyl, and- (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which aryl is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence is selected from-H, -C₁-C₆Alkyl, hydroxy C₁-C₆Alkyl, amino C₁-C₆Alkyl, halo C₁-C₆Alkyl, -C₃-C₇Cycloalkyl, - (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl), -aryl, -heteroaryl and-heterocycloalkyl, wherein the aryl is optionally substituted at each occurrence with 1, 2 or 3R₂₇₀Each heteroaryl group optionally substituted with 1, 2, 3 or 4R ₂₀₀Substituted, each heterocycloalkyl optionally substituted with 1, 2, 3 or 4R₂₁₀Is substituted in which

R₂₇₀Independently at each occurrence is R₂₀₅；C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; NR (nitrogen to noise ratio)₂₃₅R₂₄₀；OH；C≡N；-CO-(C₁-C₄Alkyl groups); and ═ O, where heterocycloalkyl is optionally substituted at each occurrence with 1, 2, or 3R₂₀₅Substituted by groups; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₀₅Substituted by groups;

R₂₄₅and R₂₅₀Independently at each occurrence selected from H, C₁-C₄Alkyl radical、C₁-C₄Hydroxyalkyl radical, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, or

R₂₅₅and R₂₆₀Independently at each occurrence is selected from: h; c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (CH)₂)_0-4-C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (C)₁-C₄Alkyl) -aryl; - (C)₁-C₄Alkyl) -heteroaryl; - (C)₁-C₄Alkyl) -heterocycloalkyl; -an aryl group; -a heteroaryl group; -a heterocycloalkyl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-an aryl group; - (CH) ₂)_1-4-R₂₆₅-(CH₂)_0-4-a heteroaryl group; and- (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-heterocycloalkyl, wherein

R₂₆₅Independently at each occurrence is-O-, -S-or-N (C)₁-C₆Alkyl) -;

each aryl or phenyl group is optionally substituted with 1, 2 or 3 groups which are independently R₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group.

Preferred compounds of formula I-2 include those wherein

R_CIs- (CR)₂₄₅R₂₅₀)_0-4-aryl or- (CR)₂₄₅R₂₅₀)_0-4Heteroaryl, wherein aryl and heteroaryl are notOptionally substituted by 1, 2 or 3R₂₀₀And (4) substituting the group.

Preferred compounds of formula I-2 also include those in which

R_CIs- (CR)₂₄₅R₂₅₀) -aryl or- (CR)₂₄₅R₂₅₀) Heteroaryl, wherein each aryl and heteroaryl is optionally substituted by 1, 2 or 3R₂₀₀And (4) substituting the group.

Preferred compounds of formula I-2 also include those in which

Preferred compounds of formula I-2 also include those wherein R is_CIs benzyl.

Other preferred compounds of formulae I, I-1 and I-2 include compounds of formula I-3, that is, those represented by formula I, I-1 or I-2, wherein

R_NThe method comprises the following steps:

wherein

R₄Is NH₂、-NH-(CH₂)_n6-R_4-1、-NHR₈、-NR₅₀C(O)R₅or-NR₅₀CO₂R₅₁；

Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R₄-₂And R₄-₃Independently is H, C₁-C₃Alkyl or C₃-C₆A cycloalkyl group;

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR ₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen、CN、NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group. Preferred compounds of formula I-3 include those wherein

R_NIs that

Wherein

X is C₁-C₄Alkylene, optionally substituted with 1, 2 or 3 methyl groups; or-NR _4-6-, or

R₄And R_4-6Combined to form- (CH)₂)_n10-, wherein

n₁₀Is 1, 2, 3 or 4;

z is selected from the group consisting of a bond, SO₂SO, S and C (O);

y is selected from H; c₁-C₄A haloalkyl group; c₅-C₆Heterocycloalkyl containing at least one of N, O or S; a phenyl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl and halogen; an alkoxy group; phenyl, optionally halogenatedElement, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; phenyl radical C₁-C₄Alkyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; wherein

Y₁And Y₂Are identical or different and are H; c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C₁-C₄Alkoxy radical, C₃-C₈Cycloalkyl and OH; c₂-C₆An alkenyl group; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; phenyl radical C₁-C₄An alkyl group; and C₃-C₈Cycloalkyl radical C₁-C₄Alkyl, or

Preferred compounds of formula I-3 include those wherein

X is C₁-C₄Alkylene, optionally substituted with 1, 2 or 3 methyl groups;

z is selected from SO₂SO, S and C (O);

Preferred compounds of formula I-3 include those wherein R is_NThe method comprises the following steps:

wherein

n⁶Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group; and is

R₅₁Selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionallySubstituted by 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group;

y is C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy.

Preferred compounds of formula I-3 further include those wherein

Each aryl group is optionally substituted by 1, 2 or 3R₂₀₀Substitution;

R₂₀₀independently at each occurrence is C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO₂(ii) a Halogen; -CO₂H；C≡N；-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-CO₂R₂₁₅(ii) a Or- (CH)₂)_0-4-O- (C optionally substituted by 1, 2, 3 or 5-F)₁-C₆Alkyl groups);

R₂₁₅independently at each occurrence is C₁-C₆Alkyl, - (CH)₂)_0-2- (phenyl), C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which the phenyl group is optionally substituted at each occurrence by 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally present at each occurrenceBy 1, 2 or 3R₂₁₀Substitution;

Preferred compounds of formula I-3 include those wherein

R₂and R₃Independently selected from H or C₁-C₄Alkyl, optionally substituted with 1 substituent selected from the group consisting of halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, NH₂、NH(C₁-C₆Alkyl) and NH (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R_Cis C₁-C₈Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-SH、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C_3-8) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO²H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-phenyl, optionally substituted by 1, 2 or 3R₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-a pyridyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyridazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrimidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a furyl group; - (CR)₂₄₅R₂₅₀)_0-3-an indolyl group; - (CR)₂₄₅R₂₅₀)_0-3-thienyl; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrazolyl group; - (CR)₂₄₅R₂₅₀)_0-3-a benzoxazolyl group; - (CR)₂₄₅R₂₅₀)_0-3Imidazolyl optionally substituted by 1, 2, 3 or 4R for each of the above heteroaryl groups₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-imidazolidinyl; - (CR)₂₄₅R₂₅₀)_0-3-a tetrahydrofuranyl group; - (CR)₂₄₅R₂₅₀)_0-3-a tetrahydropyranyl group; - (CR)₂₄₅R₂₅₀)_0-3-a piperazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a piperidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-indolyl, each of said heterocycloalkyl optionally substituted by 1, 2, 3 or 4R ₂₁₀Substitution; - (CH)₂)_0-1-CH((CH₂)_0-4-OH)-(CH₂)_0-1-a phenyl group; - (CH)₂)_0-1-CH(C₁-C₄Hydroxyalkyl) - (CH₂)_0-1-a pyridyl group;

R₂₁₅independently at each occurrence is C₁-C₆Alkyl, - (CH)₂)_0-2- (phenyl), C₃-C₆Cycloalkyl, - (CH)₂)_0-2- (pyridyl), - (CH)₂)_0-2- (pyrrolyl), - (CH)₂)_0-2- (imidazolyl), - (CH)₂)_0-2- (pyrimidinyl),-(CH₂)_0-2- (pyrrolidinyl), - (CH)₂)_0-2- (imidazolidinyl), - (CH)₂)_0-2- (piperazinyl), - (CH)₂)_0-2- (piperidinyl) and- (CH)₂)_0-2- (morpholinyl) wherein phenyl is optionally substituted at each occurrence by 1 or 2 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein each heterocycloalkyl group is optionally substituted at each occurrence with 1 or 2R ₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence by 1 or 2R₂₁₀Substitution;

Other preferred compounds of formula I-3 include those wherein

X is-C₁-C₃Alkylene, optionally substituted with 1 or 2 methyl groups;

z is SO₂SO, S and C (O);

y is C₁-C₄A haloalkyl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl radicals, not containingOptionally substituted by 1 or 2 substituents, which may be the same or different, selected from halogen, hydroxy, C₁-C₄Alkoxy radical, C₁-C₄Thioalkoxy and C₁-C₄A haloalkoxy group; c₁-C₄An alkoxy group; phenyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; and benzyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; wherein

Y₁And Y₂Are identical or different and are H; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C ₁-C₂Alkoxy radical, C₃-C₆Cycloalkyl and OH; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; a benzyl group; and C₃-C₆Cycloalkyl radical C₁-C₂Alkyl, or

Preferred compounds of formula I-3 also include those represented by formula I-4, i.e., compounds of formula I-3 wherein

X is-C₁-C₃Alkylene, optionally substituted with 1 methyl group;

z is SO₂SO, S and C (O);

y is OH; -N (Y)₁)(Y₂) (ii) a A phenyl group; a benzyl group; or C₁-C₁₀Alkyl optionally substituted with 1 or 2 substituentsMay be the same or different and is selected from the group consisting of halogen, hydroxy, methoxy, ethoxy, thiomethoxy, thioethoxy and CF₃(ii) a Wherein

R₁is benzyl optionally substituted with 1, 2 or 3 groups independently selected from methyl, ethyl, n-propyl, isopropyl, hydroxymethyl, monohalomethyl, dihalomethyl, trihalomethyl, -CH₂CF₃Methoxymethyl, halogen, methoxy, ethoxy, n-propoxy, isopropoxy and OH;

R₂and R₃Independently selected from H or C₁-C₄An alkyl group;

R₂₀₀at each timeIndependently at the occurrence is selected from C₁-C₄Alkyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; OH; and halogen;

Preferred compounds of formulae I, I-1 and I-2 include compounds of formula I-5, that is, those represented by formula I, I-1 or I-2, wherein

R_Nis-C (═ O) - (CRR')_0-6R₁₀₀；

R₁₀₀Represents aryl, heteroaryl OR heterocyclyl, wherein the ring part of each group is optionally substituted by 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH²)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C¹-C⁶Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Preferred compounds of formula I-5 include those wherein

R_Nis-C (═ O) -R₁₀₀；

R₁₀₀Represents aryl OR heteroaryl, wherein the ring part of each group is optionally substituted by 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH²)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)₀-₄-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH) ₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Preferred compounds of formula I-5 also include those wherein

R_Nis-C (═ O) -aryl OR-C (═ O) -heteroaryl, wherein the cyclic moiety of each group is optionally substituted with 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Other preferred compounds of formula I-5 include those wherein

R_Nis-C (═ O) -aryl or-C (═ O) -heteroaryl, wherein the cyclic moiety of each group is optionally substituted with 1 or 2 groups independently selected from C₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl, - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₀) Alkynyl.

Other preferred compounds of formula I-5 also include those wherein R is_NThe method comprises the following steps:

wherein sub is hydrogen or C₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl, - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₀) Alkynyl.

Preferred stereochemistry of compounds of formula I are as follows:

preferred compounds of formula X include those represented by formula X-1, that is, compounds of formula X wherein

R₁Is aryl, heteroaryl, heterocyclyl-C ₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected fromHalogen, -OH, -SH, -C.ident.N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR', or-N (R) SO₂R′、-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

Preferred compounds of the formula X-1 also include those in which

R₁is-C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups which are independentlySelected from the group consisting of halogen, -OH, -SH, -C.ident.N, -NO₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR', or-N (R) SO₂R′、-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, C ₁-C₆Alkyl and mono-or dialkylamino; and the heterocyclyl is optionally further substituted by oxo.

Preferred compounds of the formula X-1 further include those wherein

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF ₃、C₁-C₃Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and the heterocyclyl is optionally further substituted by oxo.

Preferred compounds of the formula X-1 also include those in which

Preferred compounds of the formula X-1 further include those wherein

Preferred compounds of the formula X-1 include those in which

Preferred compounds of the formula X-1 also include those wherein R₁Is benzyl or 3, 5-difluorobenzyl.

Preferred compounds of formula X and X-1 include those represented by formula X-2, that is, compounds of formula X or X-1 wherein

Preferred compounds of the formula X-2 include those in which

R_CSelected from: c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_0-2(C₁-C₆Alkyl), -SH, -NR₂₃₅C＝ONR₂₃₅R₂₄₀、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-an aryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - [ C (R)₂₅₅)(R₂₆₀)]_1-3-CO-N-(R₂₅₅)₂(ii) a -CH (aryl)₂(ii) a -CH (heteroaryl)₂(ii) a -CH (heterocycloalkyl)₂(ii) a -CH (aryl) (heteroaryl); -CO-NR₂₃₅R₂₄₀；-(CH₂)_0-1-CH((CH₂)_0-6-OH)-(CH₂)_0-1-an aryl group; - (CH)₂)_0-1-CHR_C-6-(CH₂)_0-1-a heteroaryl group; -CH (-aryl or-heteroaryl) -CO-O (C)₁-C₄Alkyl groups); -CH (-CH)₂-OH) -CH (OH) -phenyl-NO₂；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; -CH₂-NH-CH₂-CH(-O-CH₂-CH₃)₂(ii) a -H; and- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R₂₀₀Substitution;

R₂₀₀independently at each occurrence is selected from: c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; OH; -NO ₂(ii) a Halogen; -CO₂H；C≡N；-(CH₂)_0-4-CO-NR₂₂₀R₂₂₅；-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl groups); - (CH)₂)_0-4-CO₂R₂₁₅(ii) a And- (CH)₂)_0-4-O- (C optionally substituted by 1, 2, 3 or 5-F)₁-C₆Alkyl groups);

R₂₁₅independently at each occurrence is selected from C₁-C₆Alkyl, - (CH)₂)_0-2- (aryl), C₃-C₇Cycloalkyl, and- (CH) ₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which aryl is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence is selected from-H, -C₁-C₆Alkyl, hydroxy C₁-C₆Alkyl, amino C₁-C₆Alkyl, halo C₁-C₆Alkyl, -C₃-C₇Cycloalkyl, - (C)₁-C₆Alkyl) -O- (C₁-C³Alkyl), -aryl, -heteroaryl and-heterocycloalkyl, wherein the aryl is optionally substituted at each occurrence with 1, 2 or 3R₂₇₀Each heteroaryl group optionally substituted with 1, 2, 3 or 4R₂₀₀Substituted, each heterocycloalkyl optionally substituted with 1, 2, 3 or 4R₂₁₀Is substituted in which

R₂₇₀Independently at each occurrence is R₂₀₅；C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; NR (nitrogen to noise ratio)₂₃₅R₂₄₀；OH；C≡N；-CO-(C₁-C₄Alkyl groups); and ═ O, where heterocycloalkyl is present at each occurrenceOptionally at the time by 1, 2 or 3R₂₀₅Substituted by groups; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₀₅Substituted by groups;

R₂₃₅and R₂₄₀Independently at each occurrence is H or C ₁-C₆An alkyl group;

R₂₆₅Independently at each occurrence is-O-, -S-or-N (C)₁-C₆Alkyl) -;

each aryl or phenyl group is optionally substituted with 1, 2 or 3 groups which are independentlyGround is R₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group.

Preferred compounds of the formula X-2 include those in which

Preferred compounds of formula X-2 also include those wherein

Preferred compounds of formula X-2 also include those wherein R is_CIs benzyl.

Other preferred compounds of formulae X, X-1 and X-2 include compounds of formula X-3, that is, those represented by formula X, X-1 or X-2, wherein

R_NThe method comprises the following steps:

wherein

R⁴Is NH²、-NH-(CH₂)_n6-R_4-1、-NHR₈、-NR₅₀C(O)R₅or-NR₅₀CO₂R₅₁；

Wherein

n₆Is 0, 1, 2 or 3;

n₇Is 0, 1, 2 or 3;

R_4-1is selected from-SO₂-(C₁-C₈Alkyl), -SO- (C)₁-C₈Alkyl), -S- (C)₁-C₈Alkyl), -S-CO- (C)₁-C⁶Alkyl), -SO₂-NR_4-2R_4-3、-CO-C₁-C₂Alkyl, -CO-NR_4-3R_4-4；

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C ₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R⁸selected from: -SO₂-heteroaryl, optionally substituted with 1 or 2 groups, which are independently C₁-C₄Alkyl or halogen; -SO₂-an aryl group; -SO₂-a heterocycloalkyl group; -C (O) NHR₉(ii) a A heterocycloalkyl group; -S-C₂-C₄Alkanoyl radical of which

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl, optionally substituted by 1, 2 or 3 groupsThe radicals are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group.

Preferred compounds of formula X-3 include those wherein

R_NIs that

Wherein

R₄And R_4-6Combined to form- (CH)₂)_n10-, wherein

n₁₀Is 1, 2, 3 or 4;

z is selected from the group consisting of a bond, SO₂SO, S and C (O);

y is selected from H; c₁-C₄A haloalkyl group;C₅-C₆heterocycloalkyl containing at least one of N, O or S; a phenyl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c ₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl and halogen; an alkoxy group; phenyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; phenyl radical C₁-C₄Alkyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; wherein

Preferred compounds of formula X-3 include those wherein

X is C₁-C₄Alkylene, optionally substituted with 1, 2 or 3 methyl groups;

z is selected from SO₂SO, S and C (O);

y is selected from H; c₁-C₄A haloalkyl group; c₅-C₆Heterocycloalkyl containing at least one of N, O or S; a phenyl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c ₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C₁-C₃Alkyl and halogen; an alkoxy group; phenyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; phenyl radical C₁-C₄Alkyl, optionally substituted by halogen, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, CN or NO₂Substitution; wherein

Preferred compounds of formula X-3 includeCompound (I) wherein R_NThe method comprises the following steps:

wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4Is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C ₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group; and is

R₅₁Selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group;

Preferred compounds of formula X-3 further include those wherein

R_CIs C₁-C₈Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_0-2(C₁-C₆Alkyl), -SH, -C ═ ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-a phenyl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - (CH)₂)_0-1-CH((CH₂)_0-4-OH)-(CH₂)_0-1-a phenyl group; - (CH)₂)_0-1-CHR_C-6-(CH₂)_0-1-a heteroaryl group; -CH (-CH) ₂-OH) -CH (OH) -phenyl-NO₂；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; or- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R₂₀₀Substitution;

R₂₁₀independently at each occurrence is C₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; halogen; c₁-C₆An alkoxy group; c₁-C₆A haloalkoxy group; -NR₂₂₀R₂₂₅；OH；C≡N；C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; -CO- (C)₁-C₄Alkyl groups); -SO₂-NR₂₃₅R₂₄₀；-CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); and ═ O;

R₂₁₅independently at each occurrence is C₁-C₆Alkyl, - (CH)₂)_0-2- (phenyl), C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which the phenyl group is optionally substituted at each occurrence by 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R ₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₃₅and R₂₄₀Independently at each occurrence is H or C₁-C⁶An alkyl group;

Preferred compounds of formula X-3 include those wherein

R₁Is benzyl optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, C₁-C₄Alkoxy, hydroxy and C₁-C₄Alkyl, optionally substituted by 1, 2 or 3 halogen, OH, SH, NH₂、NH(C₁-C₆Alkyl), N- (C)₁-C₆Alkyl) (C₁-C₆Alkyl), C.ident. N, CF₃Substitution;

R_Cis C₁-C₈Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R ₂₀₅、-SH、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-phenyl, optionally substituted by 1, 2 or 3R₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-a pyridyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyridazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrimidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a furyl group; - (CR)₂₄₅R₂₅₀)_0-3-an indolyl group; - (CR)₂₄₅R₂₅₀)_0-3-thienyl; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrazolyl group; - (CR)₂₄₅R₂₅₀)_0-3-a benzoxazolyl group; - (CR)₂₄₅R₂₅₀)_0-3Imidazolyl optionally substituted by 1, 2, 3 or 4R for each of the above heteroaryl groups₂₀₀Substitution; - (CR)₂₄₅R₂₅₀)_0-3-imidazolidinyl; - (CR)₂₄₅R₂₅₀)_0-3-a tetrahydrofuranyl group; - (CR)₂₄₅R₂₅₀)_0-3-a tetrahydropyranyl group; - (CR)₂₄₅R₂₅₀)_0-3-a piperazinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a pyrrolidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-a piperidinyl group; - (CR)₂₄₅R₂₅₀)_0-3-indolyl, each of said heterocycloalkyl optionally substituted by 1, 2, 3 or 4R₂₁₀Substitution; - (CH)₂)_0-1-CH((CH₂)_0-4-OH)-(CH₂)_0-1-a phenyl group; - (CH)₂)_0-1-CH(C₁-C₄Hydroxyalkyl) - (CH₂)_0-1-a pyridyl group;

R₂₀₅independently at each occurrence is C₁-C₆Alkyl, halogen, -OH, -O-phenyl, -SH, -C ≡ N, -CF₃、C₁-C₆Alkoxy, NH₂、NH(C₁-C₆Alkyl) and N- (C) ₁-C₆Alkyl) (C₁-C₆Alkyl groups);

R₂₁₅independently at each occurrence is C₁-C₆Alkyl, - (CH)₂)_0-2- (phenyl), C₃-C₆Cycloalkyl, - (CH)₂)_0-2- (pyridyl), - (CH)₂)_0-2- (pyrrolyl), - (CH)₂)_0-2- (imidazolyl), - (CH)₂)_0-2- (pyrimidinyl), - (CH)₂)_0-2- (pyrrolidinyl), - (CH)₂)_0-2- (imidazolidinyl), - (CH)₂)_0-2- (piperazinyl), - (CH)₂)_0-2- (piperidinyl) and- (CH)₂)_0-2- (morpholinyl) wherein phenyl is optionally substituted at each occurrence by 1 or 2 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein each heterocycloalkyl group is optionally substituted at each occurrence with 1 or 2R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence by 1 or 2R₂₁₀Substitution;

Other preferred compounds of formula X-3 include those wherein

X is-C₁-C₃Alkylene, optionally substituted with 1 or 2 methyl groups;

z is SO₂SO, S and C (O);

Y₁And Y₂Are identical or different and are H; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C₁-C₂Alkoxy radical, C₃-C₆Cycloalkyl and OH; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; a benzyl group; and C₃-C₆Cycloalkyl radical C₁-C₂Alkyl, or

-N(Y₁)(Y₂) Form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1, 2, 3 or 4 groups independently C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C ₁-C₆Alkyl or halogen.

Preferred compounds of formula X-3 also include those represented by formula X-4, that is, compounds of formula X-3 wherein

X is-C₁-C₃Alkylene, optionally substituted with 1 methyl group;

z is SO₂SO, S and C (O);

-N(Y₁)(Y₂) Form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1 or 2 groups, which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy or halogen;

R₂And R₃Independently selected from H or C₁-C₄An alkyl group;

R₂₁₀independently at each occurrence is selected from C₁-C₄Alkyl, optionally substituted by 1 or 2R₂₀₅Substituted by groups; halogen; c₁-C₄An alkoxy group; OCF₃；NH₂；NH(C₁-C₆Alkyl groups); n (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); OH; and-CO- (C)₁-C₄Alkyl groups);

Preferred compounds of formulae X, X-1 and X-2 include compounds of formula X-5, that is, those represented by formula X, X-1 or X-2, wherein

R_Nis-C (═ O) - (CRR')_0-6R₁₀₀；

R₁₀₀Represents aryl, heteroaryl OR heterocyclyl, wherein the ring part of each group is optionally substituted by 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-CO-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Preferred compounds of formula X-5 include those wherein

R_Nis-C (═ O) -R₁₀₀；

R₁₀₀Represents aryl OR heteroaryl, wherein the ring part of each group is optionally substituted by 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF³、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Preferred compounds of the formula X-5 also include those in which

R_Nis-C (═ O) -aryl OR-C (═ O) -heteroaryl, wherein the cyclic moiety of each group is optionally substituted with 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH) ₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C₆Alkyl), - (CH)₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl or (C)₂-C₁₀) Alkynyl.

Other preferred compounds of formula X-5 include those wherein

Other preferred compounds of formula X-5 also include those wherein R is_NThe method comprises the following steps:

Preferred stereochemistry of compounds of formula X are as follows:

in another aspect, the invention provides intermediates of formula (IA):

wherein R is₁、R₂、R₃、R_NAnd R_CIs as defined above for formula I, PROT is an amine protecting group as defined below.

In another aspect, the invention provides intermediates of formula (XA):

The invention also provides methods of producing compounds of formula (Y) from compounds of formula (AA), formula (I) or formula (X), which are useful for treating and/or preventing Alzheimer's disease. The formation of the compound of formula (Y) from the compound of formula (AA), (I) or (X) may occur in vivo or in vitro.

The invention also provides a process for converting a compound of formula AA, I or X to a compound of formula Y by contacting the compound of formula AA, I or X with an aqueous medium. Transformation may occur in vitro or in vivo.

The present invention also provides the following methods: treating a patient having or preventing a disease or condition selected from alzheimer's disease, helping to prevent or delay the onset of alzheimer's disease, treating a patient with Mild Cognitive Impairment (MCI) and preventing or delaying the onset of alzheimer's disease in a patient who will progress from MCI to AD, treating down's syndrome, treating a patient with hereditary cerebral hemorrhage with amyloidosis of the dutch-type, treating cerebral amyloid angiopathy and preventing its underlying consequences, i.e., single and recurrent cerebral lobe bleeding, treating other degenerative dementias, including dementia of mixed vascular and degenerative origin, dementia associated with parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with corticobasal degeneration or diffuse lewy alzheimer's disease, in need of such treatment, comprising administering a therapeutically effective amount of a compound of formula (AA), (I) Or (X) administration of a compound or a pharmaceutically acceptable salt thereof.

In one embodiment, this method of treatment can be for alzheimer's disease.

In one embodiment, such a method of treatment may be used to help prevent or delay the onset of Alzheimer's disease.

In one embodiment, this method of treatment may be for mild cognitive impairment.

In one embodiment, this method of treatment may be for down syndrome.

In one embodiment, this method of treatment may be used for hereditary cerebral hemorrhage with amyloidosis of the dutch-type.

In one embodiment, this method of treatment may be for cerebral amyloid angiopathy.

In one embodiment, this method of treatment may be used for degenerative dementia.

In one embodiment, this method of treatment can be used to diffuse lewy body type alzheimer's disease.

In one embodiment, the method of treatment can treat an existing disease.

In one embodiment, the method of treatment can prevent the development of disease.

In one embodiment, the method of treatment may employ the following therapeutically effective amounts: for oral administration, from about 0.1 mg/day to about 1,000 mg/day; from about 0.5 to about 100 mg/day for parenteral, sublingual, intranasal, intrathecal administration; from about 0.5 mg/day to about 50 mg/day for depot administration and implants; for topical administration, from about 0.5 mg/day to about 200 mg/day; for rectal administration, from about 0.5mg to about 500 mg.

In one embodiment, the method of treatment may employ the following therapeutically effective amounts: for oral administration, from about 1 mg/day to about 100 mg/day; for parenteral administration, from about 5 to about 50mg per day.

In one embodiment, the method of treatment may employ the following therapeutically effective amounts: for oral administration, from about 5 mg/day to about 50 mg/day.

The invention also includes pharmaceutical compositions comprising a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof.

The invention also includes the use of a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament.

The invention also includes the following methods: inhibiting beta-secretase activity; inhibiting the cleavage of Amyloid Precursor Protein (APP) in the reaction mixture at a cleavage site between Met596 and Asp597 numbered according to the APP-695 amino acid isoform, or at a corresponding site of its isoform or mutant; inhibiting the production of amyloid beta peptide (a β) in a cell; inhibiting the production of beta-amyloid plaques in an animal; treating or preventing a disease characterized by amyloid-beta deposits in the brain. Each of these methods comprises administering a therapeutically effective amount of a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof.

The invention also includes a method of inhibiting β -secretase activity comprising exposing the β -secretase enzyme to a compound of formula (AA), (I) or (X) under conditions such that an effective inhibitory amount of the compound of formula (Y) or a pharmaceutically acceptable salt thereof is produced.

In one embodiment, the method employs a compound that inhibits 50% of the enzymatic activity at a concentration of less than 50 micromolar.

In one embodiment, the method employs a compound that inhibits 50% of enzyme activity at a concentration of 10 micromolar or less.

In one embodiment, the method employs a compound that inhibits 50% of enzyme activity at a concentration of 1 micromolar or less.

In one embodiment, the method employs a compound that inhibits 50% of enzyme activity at a concentration of 10 nanomolar or less.

In one embodiment, such a method comprises exposing the β -secretase enzyme to the compound in vitro.

In one embodiment, such a method comprises exposing the β -secretase enzyme to the compound in a cell.

In one embodiment, such a method comprises exposing the β -secretase enzyme to the compound in an animal cell.

In one embodiment, such a method comprises exposing the β -secretase enzyme to the compound in a human.

The invention also includes a method of inhibiting the cleavage of Amyloid Precursor Protein (APP) in a reaction mixture at a cleavage site between Met596 and Asp597, numbered according to the APP-695 amino acid isoform, or at a corresponding site of a isoform or mutant thereof, comprising exposing said reaction mixture to an effective inhibiting amount of a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof.

In one embodiment, this method employs the following cleavage sites: between Met652 and Asp653, numbered homotype according to APP-751; between Met671 and Asp672 numbered homotype according to APP-770; between Leu596 and Asp597 of the APP-695 Swedish mutation; between Leu652 and Asp653 of the Swedish mutation of APP-751; or between Leu671 and Asp672 of the Swedish mutation of APP-770.

In one embodiment, such a method exposes the reaction mixture in vitro.

In one embodiment, such a method exposes the reaction mixture in the cell.

In one embodiment, such a method exposes the reaction mixture in an animal cell.

In one embodiment, such a method exposes the reaction mixture to human cells.

The invention also includes a method of inhibiting the production of amyloid beta peptide (a β) in a cell comprising administering to the cell a compound of formula (AA), (I) or (X) under conditions such that an effective inhibitory amount of the compound of formula (Y) or a pharmaceutically acceptable salt thereof is produced.

In one embodiment, the method comprises administering to the animal.

In one embodiment, the method comprises administering to a human.

The invention also includes a method of inhibiting the production of β -amyloid plaques in an animal comprising administering to the animal a compound of formula (AA), (I) or (X) under conditions wherein an effective inhibitory amount of the compound of formula (Y) or a pharmaceutically acceptable salt thereof is produced.

In one embodiment, the method comprises administering to a human.

The invention also includes a method of treating or preventing a disease characterized by amyloid-beta deposits in the brain comprising administering to a patient a therapeutically effective amount of a compound of formula (AA), (I) or (X) under conditions such that an effective inhibitory amount of the compound of formula (Y) or a pharmaceutically acceptable salt thereof is produced.

In one embodiment, the method produces a compound of formula (Y) that inhibits 50% of enzyme activity at a concentration of less than 50 micromolar.

In one embodiment, the method produces a compound of formula (Y) that inhibits 50% of enzyme activity at a concentration of 10 micromolar or less.

In one embodiment, the method produces a compound of formula (Y) that inhibits 50% of enzyme activity at a concentration of 1 micromolar or less.

In one embodiment, the method produces a compound of formula (Y) that inhibits 50% of enzyme activity at a concentration of 10 nanomolar or less.

In one embodiment, such methods employ a therapeutic amount of the compound in the range of about 0.1 to about 1500 mg/day.

In one embodiment, such methods employ a therapeutic amount of the compound in the range of about 15 to about 1000 mg/day.

In one embodiment, such methods employ a therapeutic amount of the compound in the range of about 1 to about 100 mg/day.

In one embodiment, such methods employ a therapeutic amount of the compound in the range of about 5 to about 50 mg/day.

In one embodiment, such a method can be used for Alzheimer's disease.

In one embodiment, this method may be used for mild cognitive impairment, down's syndrome, or hereditary cerebral hemorrhage with amyloidosis of the dutch type.

The invention also includes a kit of parts comprising components capable of being assembled wherein at least one of the components comprises a compound of formula AA, I or X enclosed in a container.

In one embodiment, such a kit of parts comprises the lyophilized compound and at least one additional component comprises a diluent.

The invention also provides a container kit comprising a plurality of containers, each container comprising one or more unit doses of a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof.

In one embodiment, such a container kit comprises each container suitable for oral delivery and comprises a tablet, gel or capsule.

In one embodiment, such container kits comprise containers each suitable for parenteral delivery and include stock products, syringes, ampoules or vials.

In one embodiment, such a container kit comprises each container suitable for topical delivery and comprises a patch, pad, ointment or cream.

The invention also provides a kit of parts comprising a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof; and one or more therapeutic agents selected from the group consisting of antioxidants, anti-inflammatory agents, gamma secretase inhibitors, neurotrophic agents, acetylcholinesterase inhibitors, statins (statins), a β peptides, and anti-a β antibodies.

The invention also includes a composition comprising a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof; and an inert diluent or an edible carrier.

In one embodiment, the composition includes an oil vehicle.

The invention also includes a composition comprising a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof; and a binder, excipient, disintegrant, lubricant or glidant (gildant).

The invention also includes a composition comprising a compound of formula (AA), (I) or (X), or a pharmaceutically acceptable salt thereof; it is present in a cream, ointment or patch.

The present invention provides compounds of formula (AA), formula (I) and formula (X) which can be used to produce compounds of formula (Y) useful in the treatment and prevention of Alzheimer's disease. The compounds of the present invention can be prepared by those skilled in the art based solely on the knowledge of the chemical structure of the compounds. The chemistry of the preparation of the compounds of the invention is known to those skilled in the art. In fact, there is more than one method of preparing the compounds of the present invention. Specific examples of preparation methods can be found in the art. See, e.g., J.org.chem.1998, 63, 4898-; chem.1997, 62, 9348-9353; chem.1996, 61, 5528-; med, chem, 1993, 36, 320-330; J.Am.chem.Soc.1999, 121, 1145-1155 and references cited therein. See also U.S. patent nos. 6,150,530, 5,892,052, 5,696,270 and 5,362,912 and references cited therein, which are incorporated herein by reference.

Examples of various processes that may be used to prepare the compounds of the present invention are described below.

General methods for preparing compounds of formula I and X are described in reaction scheme A. The chemical principle is straightforward and comprises, in summary, the following steps: n-protection of the starting amino acid (A) to give the corresponding protected amino acid (II), reaction of the protected amino acid (II) with diazomethane, followed by addition of a carbon atom to give the corresponding protected compound (III), reduction of the protected halide to the corresponding alcohol (IV) to give the corresponding epoxide (V), reaction with a C-terminal amine R_C-NH₂(VI) opening of the epoxide (V) to give the corresponding protected alcohol (VII).

The compounds of formula (I) may be prepared by reacting a protected alcohol (VII) with an amide-forming agent such as (R)_N-)₂O or R_N-X or R_NOH (IX) to give the alcohol (IA). The nitrogen protecting group of alcohol (IA) is then removed to yield the corresponding compound of formula (I).

The compound of formula (X) may be prepared by further N-protecting the alcohol (VII) to form the unprotected alcohol (XB). Reacting a doubly protected alcohol (XB) with an amide forming agent such as (R)_N-)₂O or R_N-X or R_N-OH (IX) to produce compound (XA). The nitrogen protecting group of compound (XA) is then removed to yield the corresponding compound of formula (X).

Those skilled in the art will appreciate that these are all known reactions in organic chemistry. Those skilled in the art, knowing the chemical structures of the compounds (AA), (I) and (X) of the invention, will be able to prepare them from known starting materials using known methods, without any additional information. The following explanation is therefore not necessary, but is helpful to the person skilled in the art who needs to prepare the compounds of the invention.

The compounds of formulae (AA), (I) and (X) can be readily prepared from intermediate (VII), whose backbone can be regarded as the hydroxyethylamine moiety-NH-CH (R) -CH (OH) -. Such frameworks can be prepared by methods known in the literature and known to the person skilled in the art. For example, J.Med.chem., 36, 288-.

Reaction scheme a illustrates a general procedure for preparing appropriately substituted amines I and X in the present invention. The compounds of the invention are prepared starting from the corresponding amino acid (A). The amino acid (A) is known to the person skilled in the art or can be readily prepared by methods known to the person skilled in the art. The compounds of the present invention have at least two chiral centers, which results in two sets of diastereomers, each of which is racemic with respect to the entirety of at least four stereoisomers. Although the biologically active end product is derived from all stereoisomers, (S, R) configuration is preferred. The first of these chiral centers (carrying R) ₁Carbon (b) is derived from the amino acid starting material (a). It is preferred to obtain or produce the desired enantiomer from a commercial source, rather than producing an impure mixture of enantiomers, which then has to be separated. Thus, it is preferred that the process starts with an enantiomerically pure (S) -amino acid (A) which is of the same configuration as the desired X product.

In reaction scheme A, the formation of (S) -protected amino acid (II) by protection of free amine (A) is described. Amino protecting groups are known to those skilled in the art, as discussed below. See, for example, "Protecting Groups in Organic Synthesis", John Wiley and sons, New York, n.y., 1981, Chapter 7; "Protecting Groups in Organic Chemistry", Plenum Press, New York, N.Y., 1973, Chapter 2. The function of the amino-protecting group is to protect the free amino functionality (-NH) during the subsequent reaction of the (S) -amino acid (A)₂) In order to avoid that the reaction cannot proceed due to the amino group reacting and being functionalized in a way that is contradictory to the need for the free radical for the subsequent reaction or that the free amino group interferes with the reaction. When the amino protecting group is no longer needed, it is removed using methods known to those skilled in the art. By definition, the amino protecting group must be readily removable by methods known to those skilled in the art, as is known to those skilled in the art. Suitable amino protecting groups are discussed below.

The (S) -protected amino acid (II) is converted into the corresponding (S) -protected compound (III) by two different methods, depending on R₂And R₃The nature of (c).

R₂And R₃May be the same or different. Preferably, R is₂And R₃Are all-H. If R is₂And R₃Not the same, then additional chiral or stereogenic centers are added to the molecule. To generate R therein₂And R₃(III) Compounds of formula (III), all-H, reaction of the (S) -protected amino acid (II) with diazomethane, as is known to the skilled person, followed by reaction with a Compound of formula H-X₁The compound reacts to form (S) -protected compound (III). X₁including-Cl, -Br, -I, -O-tosylate, -O-mesylate, -O-iodobenzenesulfonate (nosylate), and-O-bromobenzenesulfonate. Preferably, -X₁is-Br or-Cl. Suitable reaction conditions include conducting the reaction in an inert solvent such as, but not limited to, diethyl ether, tetrahydrofuran, and the like. The reaction from (S) -protected amino acid (II) to (S) -protected compound (III) is carried out for 10 minutes to 1 day at a temperature of from about-78 ℃ to about 20-25 ℃. Preferably, the reaction is carried out for 1 to 4 hours at a temperature of-30 ℃ to-10 ℃. The process incorporates a methylene group.

Alternatively, the (S) -protected compounds of formula (III) may be prepared by first preparing (S) -protected amino acid (II) is converted into the corresponding methyl or ethyl ester according to methods established in the art, followed by the use of the compound of formula X₁-C(R₂)(R₃)-X₁Reagents and metal alkali treatment. The base acts to effect halogen-metal substitution, wherein-X undergoing substitution₁Is halogen selected from chlorine, bromine or iodine. Nucleophilic addition to ester derivatives directly gives (S) -protected compounds (III). Suitable bases include, but are not limited to, alkyl lithium, including, for example, sec-butyl lithium, n-butyl lithium, and tert-butyl lithium. The reaction is preferably carried out at low temperature, for example-78 ℃. Suitable reaction conditions include conducting the reaction in an inert solvent such as, but not limited to, diethyl ether, tetrahydrofuran, and the like. If R is₂And R₃Are both hydrogen, then X₁-C(R₂)(R₃)-X₁Examples of (b) include dibromomethane, diiodomethane, chloroiodomethane, bromoiodomethane and bromochloromethane. The person skilled in the art knows the preferred conditions required to carry out the reaction. Furthermore, if R is₂And/or R₃Is not-H, then-C (R)₂)(R₃)-X₁Addition to the ester of the (S) -protected amino acid (II) gives the (S) -protected compound (III) and a further chiral center will be incorporated in the product, provided that R₂And R₃Are not identical.

The (S) -protected compound (III) is then reduced by means known to those skilled in the art for the reduction of ketones to the corresponding secondary alcohols to give the corresponding alcohols (IV). Means and reaction conditions for reducing (S) -protected compound (III) to the corresponding alcohol (IV) include, for example, sodium borohydride, lithium borohydride, borane, diisobutylaluminum hydride, and lithium aluminum hydride. Sodium borohydride is the preferred reducing agent. The reaction is carried out for 1 hour to 3 days at temperatures from-78 ℃ to elevated temperatures up to the reflux point of the solvent used. It is preferred to carry out the reaction between-78 ℃ and 0 ℃. If a borane is used, complexes thereof, such as borane-methyl sulfide complexes, borane-piperidine complexes or borane-tetrahydrofuran complexes, may be employed. Preferred combinations of the required reducing agents and reaction conditions are known to those skilled in the art, see for example Larock, r.c., Comprehensive Organic Transformations, vchpublishes, 1989. Reduction of the (S) -protected compound (III) to the corresponding alcohol (IV) to form the second chiral center (if R₂And R₃Not the same, a third chiral center). The reduction of the (S) -protected compound (III) produces a mixture of enantiomers (S, R/S) -alcohol (IV) in the second centre. This mixture of enantiomers is then separated by means known to those skilled in the art, such as selective low temperature recrystallization or chromatographic separation, e.g. HPLC, using commercially available chiral columns. The enantiomer used in the rest of reaction scheme a is (S, S) -alcohol (IV), since this enantiomer will give the desired (S, R) -substituted compound I or X.

(S, S) -alcohol (IV) is converted into the corresponding epoxide (V) by means known to the person skilled in the art. The stereochemistry of the centers (S) - (IV) is preserved in the formation of epoxide (V). A preferred means is reaction with a base such as, but not limited to, hydroxide ions generated from sodium hydroxide, potassium hydroxide, lithium hydroxide, and the like. The reaction conditions include C₁-C₆The use of an alcohol solvent; ethanol is preferred. Conventional cosolvents, such as ethyl acetate, may also be employed. The reaction temperature is from-45 ℃ to the reflux temperature of the alcohol used; the preferred temperature range is between-20 ℃ and 40 ℃.

Preparation of wherein R₁An alternative and preferred process for epoxide (V) which is 3, 5-difluorobenzyl is described in scheme D. The first step of the process is to protect the free amino group of the (S) -amino acid (A) with an amino protecting group, as discussed previously, to produce the (S) -protected amino acid (II).

In an alternative method, the (S) -protected amino acid (A) is converted to the corresponding (S) -protected ester (XVII) in one of several ways. One method involves the use of lithium hydroxide. The (S) -protected amino acid (a) is mixed with lithium hydroxide using lithium hydroxide and cooled to-20 ℃ to about 10 ℃. Next, a methylating agent selected from the group consisting of dimethyl sulfate, methyl iodide and methyl triflate (methyl triflate) is added. More preferably, the methylating agent is dimethyl sulfate. Followed by heating to about 20 ℃ to about 50 ℃.

Alternatively, the (S) -protected amino acid (a) is contacted with a weak base, such as a bicarbonate or preferably a carbonate. Followed by the addition of a methylating agent. Heating is not necessary, but may be used to promote the reaction. The carbonate process is known to those skilled in the art. In which Z is₁For the (S) -protected ester (XVII) which is not methyl, the person skilled in the art, knowing the chemical structure, will know how to prepare the desired compound from the known starting materials. In one known method, the (S) -protected amino acid (A) is contacted with an activating agent, for example DCC, followed by addition of the appropriate alcohol Z ₁-OH. When Z is₁Is C₁-C₄Alkyl (optionally substituted), -CH₂-CH＝CH₂Or phenyl (optionally substituted), this is possible.

Reaction scheme E illustrates an alternative preparation of ester (II). In the process of reaction scheme E, an aldehyde (XX), known to those skilled in the art, is reacted with a phosphorus compound (XXI), wherein X₃Is a good leaving group to form alkene (XXII). Phosphorus compounds (XXI) are known to the person skilled in the art. Preferably, X is₃Is C₁-C₃An alkyl group; more preferably, X is₃Is C₁An alkyl group. The aldehyde (XX) and phosphate ester (XXI) are combined in an organic solvent and then cooled to about 0 ℃. A base, such as DBU or TMG, is added and the reaction mixture ingredients are warmed to 20-25 deg.C and stirred until the reaction is complete. Once the reaction is complete, it is preferred to separate the E-and Z-olefin isomers (XXII). The isolation is carried out by methods known to the person skilled in the art, for example by chromatography on silica gel. Subsequently, the olefin (XXII) is hydrogenated with a suitable hydrogenation catalyst to give the desired ester (II). Some hydrogenation reactions will yield racemic ester (II). The desired stereochemistry of ester (II) is (S) -, so it is preferred to use Z-olefin (XXII) and a hydrogenation catalyst. Preferably, the hydrogenation catalyst is of the formula [ Rh (diene) L ]⁺X^-A compound which is a mixture of a compound having a structure,

wherein Rh is rhodium;

wherein the dienes are cyclooctadiene and norbornadiene;

wherein L is DIMAP, MeDuPhos, EtDuPhos, Binaphane, f-Binaphane, Me-KetalPhos, Me-f-KetalPhos, BINAP, DIOP, BPPFA, BPPM, CHIRAPHOS, PROPHOS, NORPHOS, CYCLOPHOS, BDPP, DEGPHOS, PNNP; and wherein X^-Is ClO₄ ^-、BF₄ ^-、CF₃-SO₃ ^-、Cl^-、Br^-、PF₆ ^-And SbF₆ ^-. Preferably, the hydrogenation catalyst is DIPMAP or EtDuPhos. Suitable solvents include polar solvents, such as alcohols, preferably C₁-C₅Alcohols, and THF, more preferably methanol, ethanol, isopropanol, and THF. The chiral hydrogenation is carried out at a temperature in the range of from about-20 ℃ to about reflux. Preferably, the reaction is carried out at a temperature in the range of about 0 ℃ to about room temperature (25 ℃). The chiral hydrogenation is carried out at a pressure of from about one atmosphere to about 100 psig; more preferably, the chiral hydrogenation is carried out at a pressure of from about 10psig to about 40 psig.

Then in one of two different ways, by reacting with a slight excess of the formula CH₂ClX₂Reaction of a compound in which X₂is-Br and-I, converting the (S) -protected ester (II) to the corresponding (S) -protected ketone (III). In one approach, no exogenous nucleophiles are used. The process requires (1) the presence of three equivalents or more of a strong base having a pKb greater than about 30, followed by (2) the addition of an acid. Another process requires (1) the presence of about 2 to about 2.5 equivalents of a strong base having a pKb greater than about 30, (2) contacting the mixture of step (1) with about 1 to about 1.5 equivalents of an exogenous nucleophile, and (3) adding an acid. Suitable strong bases are those having a pKb greater than about 30. Preferably, the strong base is selected from LDA, LiHMDS and KHMDS; more preferably, the strong base is LDA. Suitable acids are those having a pKa of less than about 10. Preferably, the acid is selected from the group consisting of acetic acid, sulfuric acid, hydrochloric acid, citric acid, phosphoric acid, and benzoic acid; more preferably, the acid is acetic acid. The preferred solvent for this process is THF. The reaction may be carried out at a temperature in the range of about-80 ℃ to about-50 ℃; it is preferred to carry out the reaction at a temperature in the range of about-75 deg.C to about-65 deg.C. Suitable nucleophiles include alkyl lithium, aryl lithium, alkyl-Grignard reagents And an aryl-Grignard reagent. Preferably, the nucleophile is selected from phenyllithium, n-butyllithium, methylmagnesium bromide, methylmagnesium chloride, phenylmagnesium bromide, phenylmagnesium chloride; more preferably, the nucleophile is n-butyllithium.

The (S) -protected ketone (III) is then reduced to the corresponding (S) -alcohol (IV) by means known to the person skilled in the art for the reduction of ketones to the corresponding secondary alcohols. Means and reaction conditions for reducing (S) -protected compound (III) to the corresponding alcohol (IV) include, for example, sodium borohydride, lithium borohydride, borane, diisobutylaluminum hydride, zinc borohydride, and lithium aluminum hydride. Sodium borohydride is the preferred reducing agent. The reduction is carried out for about 1 hour to about 3 days at temperatures from about-78 ℃ to elevated temperatures up to the reflux point of the solvent used. It is preferred that the reaction be conducted at between about-78 deg.C and about 0 deg.C. If a borane is used, complexes thereof, such as borane-methyl sulfide complexes, borane-piperidine complexes or borane-tetrahydrofuran complexes, may be employed. Preferred combinations of reducing agents and reaction conditions are known to those skilled in the art, see, for example, Larock, r.c., Comprehensive organic transformations, VCH Publishers, 1989. Reduction of (S) -protected compound (III) to the corresponding alcohol (IV) generates a second chiral center. Reduction of (S) -protected compound (III) produces a mixture of diastereomers at the second center (S, R/S) -alcohol (IV). This diastereomeric mixture is then separated by means known to those skilled in the art, such as selective low temperature recrystallization or chromatographic separation, most preferably recrystallization or by using a commercially available chiral column. The diastereomer used in the rest of reaction scheme A is (S, S) -alcohol (IV) since this stereochemistry will give the desired epoxide (V).

The alcohol (IV) is converted into the corresponding epoxide (V) by means known to the person skilled in the art. The stereochemistry of the centers (S) - (IV) is preserved in the formation of epoxide (V). A preferred means is reaction with a base such as, but not limited to, hydroxide ions generated from sodium hydroxide, potassium hydroxide, lithium hydroxide, and the like. The reaction conditions include C₁-C₆The use of an alcohol solvent; ethanol is preferred. It is also possible to use the customary cosolvents, for exampleAnd (3) ethyl acetate. The reaction temperature is from-45 ℃ to the reflux temperature of the alcohol used; the preferred temperature range is between-20 ℃ and 40 ℃.

The epoxide (V) is then reacted with an appropriately substituted C-terminal amine R by means known to those skilled in the art_C-NH₂(VI) reaction, which opens the epoxide to yield the desired corresponding enantiomerically pure (S, R) -protected alcohol (VII). Substituted C-terminal amines R according to the invention_C-NH₂(VI) is commercially available or known to those skilled in the art and can be readily prepared from known compounds. Preferably, when R is_CWhen it is phenyl, it is substituted in the 3-position or 3, 5-position.

Suitable reaction conditions for opening the epoxide (V) include carrying out the reaction in a wide range of customary inert solvents. C ₁-C₆Alcohol solvents are preferred, with isopropanol being most preferred. The reaction temperature can be from 20 to 25 ℃ up to the reflux temperature of the alcohol used. The preferred temperature range for carrying out the reaction is between 50 ℃ up to the reflux temperature of the alcohol used. When the substituted C-terminal amine (VI) is cyclohexyldicarboxylic acid-1-amino-3, 5-cis-dimethyl ester, it is preferably prepared as follows. Alumina containing rhodium was added to a solution of dimethyl-5-isophthalate in acetic acid and methanol in a bomb. The bottles were saturated with 55psi hydrogen and shaken for one week. The mixture was then filtered through a thick layer of celite cake, washed three times with methanol, and the solvent removed under reduced pressure (heat) to give a concentrate. The concentrate was triturated with ether and filtered again to give the desired C-terminal amine (VI). When the substituted C-terminal amine (VI) is 1-amino-3, 5-cis-dimethoxycyclohexane, the general procedure described above is preferably followed with non-critical changes, but starting with 3, 5-dimethoxyaniline.

When the substituted C-terminal amine (VI) is aminomethyl, wherein the substituent on the methyl group is aryl, e.g. NH₂-CH₂Aryl, which is not commercially available, is preferably prepared as follows. Suitable starting materials are (appropriately substituted) aralkyl compounds. The first step is the passage of the alkyl substituent through the ring Bromination by methods known to the skilled worker is described, for example, in R.C. Larock, Comprehensive organic transformations, VCH Publishers, 1989, p.313. The alkyl halide is then reacted with the azide to form the aryl- (alkyl) -azide. Finally, the azide is reduced by hydrogen/catalyst to the corresponding amine to give the formula NH₂-CH₂-R_{C-aryl radical}The C-terminal amine (VI) of (1).

Reaction scheme B discloses an alternative method for the generation of enantiomerically pure (S, R) -protected alcohols (VII) from (S) -protected compounds (III). In an alternative process, the (S) -protected compound (III) is first reacted with the appropriately substituted C-terminal amine R using the preferred conditions described above_C-NH₂(VI) to the corresponding (S) -protected ketone (XI) and then reduced using the preferred conditions described above to the corresponding (S, R) -protected alcohol (VII).

Reaction scheme C discloses an alternative method for the generation of enantiomerically pure (S, R) -protected alcohols (VII), but this time starting from epoxides (V). In the method of reaction scheme C, an epoxide (V) is reacted with an azide to form the corresponding enantiomerically pure (S, R) -protected azide (XII). Conditions for effecting azide-mediated epoxide opening are known to those skilled in the art, see, e.g., J.March, Advanced Organic Chemistry, 3rd Edition, John Wiley &Sons Publishers, 1985, p.380. Next, the (S, R) -protected azide (XII) is reduced to the corresponding protected amine (XIII) using methods known to those skilled in the art. Preferred reduction conditions for reducing (S, R) -protected azide (XII) in the presence of a tert-butoxycarbonyl N-protecting group include catalytic hydrogenation, conditions known to those skilled in the art. Other reduction conditions for avoiding N-deprotection using protecting groups other than t-butyloxycarbonyl are known to those skilled in the art, see for example r.c. larock, comprehensive organic Transformations, VCH Publishers, 1989, p.409. Finally, by the formula R_C-X₃Nitrogen alkylation of the compounds to convert (S, R) -amines (XIII) to the corresponding protected alcohols (VII) in which X₃Is suitably thatSuch as, but not limited to, -Cl, -Br, -I, -O-mesylate, -O-tosylate, -O-triflate, and the like. X₃Or an aldehyde; coupling with (XIII) correspondingly via known reductive amination gives the protected (S, R) -alcohol (VII).

In the formation of the compounds of formula (I), the protected alcohol (VII) is reacted with an appropriately substituted amide-forming agent (IX), such as an acid anhydride, acid halide or acid, each of formula (R) by means known to those skilled in the art _N)₂O、R_NX or R_NOH (IX) to give the corresponding (S, R) -substituted amine (IA). The nitrogen acylation conditions under which the alcohol (VII) is reacted with the amide-forming agent (IX) to form the corresponding compound (IA) are known to the person skilled in the art and can be found, for example, in R.C. Larock, Comprehensive Organic Transformations, VCHPublishes, 1989, p.981, 979 and 972. Deprotection of the (S, R) -protected amine (IA) by means known to those skilled in the art for removal of amine protecting groups gives the corresponding compound (I). The means suitable for removal of the amine protecting group depends on the nature of the protecting group. Those skilled in the art who know the nature of the particular protecting group know which agent is preferred for its removal. For example, it is preferred to remove the preferred protecting group BOC by dissolving the (S, R) -protected amine (IA) in a trifluoroacetic acid/dichloromethane (1/1) mixture. When complete, the solvent was removed under reduced pressure to give the corresponding (S, R) -amine (I) (as the corresponding salt, i.e. the trifluoroacetate salt) which was used without further purification. However, if desired, the (S, R) -amines (I) can be further purified by means known to the person skilled in the art, for example by recrystallization. Furthermore, if a non-salt form is desired, it can also be obtained by means known to those skilled in the art, for example by treating the salt with mildly basic conditions to prepare the free amine. Additional BOC deprotection conditions and deprotection conditions for other protecting Groups can be found in T.W.Green and P.G.M.Wuts, "Protective Groups in organic Chemistry", John Wiley and Sons, 1991, p.309. Chemically suitable salts include trifluoroacetate, and anions of inorganic acids, such as chloride, sulfate, phosphate; preferred is trifluoro An acetate salt.

In the generation of the compound of formula (X), alcohol (VII) is further protected as described above, generating the doubly protected compound (XB). Compound (XB) is then reacted with an appropriately substituted amide forming agent (IX) to form compound (XA) as described above for compound (IA). Deprotection of the conversion of (XA) to compound (X) is carried out as described above for the conversion of compound (IA) to compound (I).

The protection of the amines is carried out, where appropriate, using methods known to the person skilled in the art. Amino protecting groups are known to those skilled in the art. See, for example, "Protecting Groups in organic Synthesis", John Wiley and sons, New York, N.Y., 1981, Chapter 7; "Protecting Groups in Organic Chemistry", Plenum Press, New York, N.Y., 1973, Chapter 2. When the amino protecting group is no longer needed, it is removed using methods known to those skilled in the art. By definition, the amino protecting group must be readily removable. There are a variety of suitable methods known to those skilled in the art; see also T.W.Green and P.G.M.Wuts, "Protective group in Organic Chemistry, John Wiley and Sons, 1991. Suitable amino protecting groups include t-butoxycarbonyl, benzyloxycarbonyl, formyl, trityl, phthalimido, trichloroacetyl, chloroacetyl, bromoacetyl, iodoacetyl, 4-phenylbenzyloxycarbonyl, 2-methylbenzyloxycarbonyl, 4-ethoxybenzyloxycarbonyl, 4-fluorobenzyloxycarbonyl, 4-chlorobenzyloxycarbonyl, 3-chlorobenzyloxycarbonyl, 2, 4-dichlorobenzyloxycarbonyl, 4-bromobenzyloxycarbonyl, 3-bromobenzyloxycarbonyl, 4-nitrobenzyloxycarbonyl, 4-cyanobenzyloxycarbonyl, 2- (4-biphenyl) isopropoxycarbonyl, 1-diphenyleth-1-yloxycarbonyl, 1-diphenylprop-1-yloxycarbonyl, trityl, benzhydryl, benzydyloxycarbonyl, benzydryloxycarbonyl, benzhydryl, 2-phenylprop-2-yloxycarbonyl, 2- (p-tolyl) prop-2-yloxycarbonyl, cyclopentyloxycarbonyl, 1-methylcyclopentyloxycarbonyl, cyclohexyloxycarbonyl, 1-methyl-cyclohexyloxycarbonyl, 2-methylcyclohexylalkoxycarbonyl, 2- (4-tolylsulfonyl) ethoxycarbonyl, 2- (methylsulfonyl) -ethoxycarbonyl, 2- (triphenylphosphino) ethoxycarbonyl, fluorenylmethoxycarbonyl, 2- (trimethylsilyl) ethoxy-carbonyl, allyloxycarbonyl, 1- (trimethylsilylmethyl) prop-1-enyloxycarbonyl, 5-benzisoxazoylmethoxycarbonyl, 4-acetoxybenzyloxycarbonyl, 2, 2, 2-trichloroethoxycarbonyl, 2-ethynyl-2-propoxycarbonyl, cyclopropylmethoxycarbonyl, 4- (decyloxy) benzyloxycarbonyl, isobornyloxycarbonyl, 1-piperidinyloxycarbonyl, 9-fluorenylmethyl carbonate, -CH ═ CH₂And phenyl-C (═ N-) -H.

Preferably, the protecting group is tert-Butoxycarbonyl (BOC) and/or benzyloxycarbonyl (CBZ), more preferably, the protecting group is tert-butoxycarbonyl. Those skilled in the art will recognize suitable methods for introducing a t-butoxycarbonyl or benzyloxycarbonyl protecting group and may additionally be referred to as T.W.Green and P.G.M.Wuts, "Protective Groups in Organic Chemistry", John Wiley and Sons, 1991 for guidance.

The compounds of the invention may contain geometric or optical isomers as well as tautomers. Thus, the present invention includes all tautomers and pure geometric isomers, such as E and Z geometric isomers, as well as mixtures thereof. Further, the invention includes both pure enantiomers and diastereomers, as well as mixtures thereof, including racemic mixtures. Individual geometric isomers, enantiomers, or diastereomers may be prepared or separated using methods known to those skilled in the art, including but not limited to chiral chromatography; preparing diastereomer by using chiral resolving agent, separating diastereomer and converting diastereomer into enantiomer.

Compounds of the invention having the indicated stereochemistry may include mixtures with other enantiomers, diastereomers, geometric isomers or tautomers, including racemic mixtures. In a preferred aspect, the content of compounds of the invention having (S, R), (S, S) or (S, R, S) stereochemistry in these mixtures is typically more than 50%. Preferably, the compounds of the invention with the indicated stereochemistry are present in these mixtures in an amount of more than 80%. More preferably, the compounds of the invention with the indicated stereochemistry are present in these mixtures in an amount of more than 90%. Even more preferably, the compounds of the invention with the specified stereochemistry are present in these mixtures in an amount of more than 99%.

The invention includes pharmaceutically acceptable salts of the compounds of formulae (AA), (I) and (X). Pharmaceutically acceptable salts are preferred over the corresponding amines of formula (AA), (I) or (X) because they result in compounds of higher water solubility, stability and/or crystallinity. Pharmaceutically acceptable salts are any salts that retain the activity of the parent compound and do not impart any deleterious or deleterious effects to the recipient and the background to which it is administered. Pharmaceutically acceptable salts include salts of inorganic and organic acids. Preferred pharmaceutically acceptable salts include the salts of the following acids: acetic acid, aspartic acid, benzenesulfonic acid, benzoic acid, bicarbonic acid, bisulfic acid, tartaric acid, butyric acid, calcium ethylenediaminetetraacetate, camphorsulfonic acid, carbonic acid, chlorobenzoic acid, citric acid, ethylenediaminetetraacetic acid, edisylic acid, estolic acid, esyl acid, esylic acid, formic acid, fumaric acid, gluceptic acid, gluconic acid, glutamic acid, hydroxyethylsulfanilic acid, hexamic acid, hexylisophthalic acid, hydrabamic acid, hydrobromic acid, hydrochloric acid, hydroiodic acid, hydroxynaphthoic acid, isethionic acid, lactic acid, lactobionic acid, maleic acid, malic acid, malonic acid, mandelic acid, methanesulfonic acid, methylnitric acid, methylsulfamic acid, muconic acid, napsylic acid, nitric acid, oxalic acid, p-nitromethanesulfonic acid, pamoic acid, pantothenic acid, phosphoric acid, monohydrogen phosphoric acid, dihydrogen phosphate, phthalic acid, polygalacturonic acid, propionic acid, salicylic acid, stearic acid, succinic acid, sulfamic acid, p-aminobenzoic acid, phthalic acid, polygalacturonic acid, propionic acid, salicylic acid, stearic acid, sulfamic acid, Sulfonic acid, sulfuric acid, tannic acid, tartaric acid, teoclic acid, and toluenesulfonic acid. For other acceptable salts see int.j.pharm., 33, 201-217(1986) and j.pharm.sci., 66(1), 1, (1977).

The present invention provides compounds, compositions, kits and methods for inhibiting beta-secretase activity and the production of A beta peptide. Inhibition of β -secretase activity can terminate or reduce the production of a β from APP, reducing or eliminating the formation of β -amyloid deposits in the brain.

Method of the invention

The compounds of the invention and pharmaceutically acceptable salts thereof are useful in treating humans or animals suffering from a condition characterized by pathological forms of β -amyloid peptide, such as β -amyloid plaques, and may also be useful in helping to prevent or delay the onset of such a condition.

The term "treatment" as used herein means that the compounds of the invention can be used in a human suffering from a disease that is at least temporarily diagnosed. The compounds of the invention will delay or delay the progression of the disease, thereby extending the life span of the individual.

The term "prophylaxis" means that the compounds of the invention are effective when administered to a patient who has not been diagnosed as likely to have the disease at the time of administration, but who is generally predicted to develop or have an increased risk of developing the disease. The compounds of the present invention will delay the development of symptoms of the disease, delay the onset of the disease, or completely prevent the individual from developing the disease. Prevention also encompasses administration of a compound of the invention to an individual thought to be predisposed to disease due to age, family history, genetic or chromosomal abnormalities, and/or due to the presence of one or more biological markers of disease, such as known mutations in the APP gene or cleavage products of APP in brain tissue or body fluids.

In the treatment or prevention of the above-mentioned diseases, the compounds of the present invention are administered in a therapeutically effective amount. The therapeutically effective amount will vary depending upon the particular compound used and the route of administration, as is known to those skilled in the art.

In treating a patient exhibiting any of the above conditions to be diagnosed, the physician may immediately administer a compound of the invention and may continue dosing indefinitely as necessary. In treating a patient who has not been diagnosed with alzheimer's disease, but who is determined to be at substantial risk of developing alzheimer's disease, the physician should preferably initiate treatment when the patient first experiences early pre-alzheimer's symptoms, such as age-related memory or cognitive problems. In addition, some patients may be identified as at risk for developing Alzheimer's disease by detecting gene markers (e.g., APOE4) or other prognostic biological indicators of Alzheimer's disease. In these cases, administration of the compounds of the invention may begin before symptoms appear, and treatment may continue indefinitely, to prevent or delay the onset of the disease, even if the patient is asymptomatic for the disease.

Dosage forms and dosages

The compounds of the invention may be administered orally, parenterally (IV, IM, depo-IM, SQ and depo SQ), sublingually, intranasally (inhalation), intrathecally, topically or rectally. Dosage forms known to those skilled in the art are suitable for delivery of the compounds of the present invention.

Compositions comprising a therapeutically effective amount of a compound of the present invention are provided. The compounds are preferably formulated in suitable pharmaceutical preparations such as tablets, capsules or elixirs for oral administration or solutions or suspensions for parenteral administration. Typically, the compounds are formulated into pharmaceutical compositions using techniques and procedures well known in the art.

According to acceptable pharmaceutical practice, about 1 to 500mg of a compound or compound mixture of the invention or a physiologically acceptable salt or ester thereof is combined with a physiologically acceptable vehicle, carrier, excipient, binder, preservative, stabilizer, flavoring agent, etc. in so-called unit dosage forms. The amount of active substance in these compositions or formulations is such that a suitable dosage within the indicated ranges is obtained. The compositions are preferably formulated in unit dosage forms containing from about 2 to about 100mg, more preferably from about 10 to about 30mg, of the active ingredient per dose. The term "unit dosage form" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient.

To prepare the compositions, one or more compounds of the present invention are combined with a suitable pharmaceutically acceptable carrier. Once the compound is mixed or added, the resulting mixture may be a solution, suspension, emulsion, or the like. Liposomal suspensions may also be suitable as pharmaceutically acceptable carriers. They can be prepared according to methods known to the person skilled in the art. The form of the resulting mixture will depend on a variety of factors, including the intended mode of administration and the solubility of the compound in the selected carrier or vehicle. An effective concentration is sufficient to alleviate or ameliorate at least one symptom of the disease, disorder or condition being treated and can be determined empirically.

Pharmaceutical carriers or vehicles suitable for administration of the compounds provided herein include any suitable carrier known to those of skill in the art for a particular mode of administration. In addition, the active ingredient may be mixed with other active ingredients that do not impair the desired effect or ingredients that supplement the desired effect or have another effect. The compound may be formulated as the sole pharmaceutically active ingredient in the composition or may be combined with other active ingredients.

If the compound exhibits insufficient solubility, solubilization can be used. Such methods are known and include, but are not limited to, the use of co-solvents, such as dimethyl sulfoxide (DMSO), the use of surfactants, such as Tween, and dissolution in aqueous sodium bicarbonate. Derivatives of the compounds, such as salts or prodrugs, may also be used to formulate effective pharmaceutical compositions.

The concentration of the compound is effective to deliver, after administration, an amount that reduces or ameliorates at least one symptom of the disorder for which the compound is useful. Typically, the compositions are formulated for single dose administration.

The compounds of the invention may be formulated with carriers that protect them from rapid elimination from the body, such as time release formulations or coatings. Such carriers include controlled release formulations such as, but not limited to, microencapsulated delivery systems. The active compound is included in a pharmaceutically acceptable carrier in an amount sufficient to exert a therapeutically effective effect on the patient being treated, without adverse side effects. Therapeutically effective concentrations can be determined empirically by testing the compound in known in vitro and in vivo model systems for the disorder being treated.

The compounds and compositions of the present invention may be packaged in a multi-dose or single-dose container. The encapsulated compounds and compositions may be provided in a kit of parts, including, for example, components that are capable of being combined for use. For example, a lyophilized form of the compound inhibitor and a suitable diluent may be provided as separate components that are combined together prior to use. The kit can include a compound inhibitor and a second therapeutic agent for co-administration. The inhibitor and the second therapeutic agent may be provided as separate components. Kits may include a plurality of containers, each container containing one or more unit doses of a compound of the invention. The container is preferably adapted to the desired mode of administration, including, but not limited to, tablets for oral administration, gel capsules, sustained release capsules, and the like; storage products for parenteral administration, pre-filled syringes, ampoules, vials and the like; and topical patch, medicated pad, cream, etc.

The concentration of the active compound in the pharmaceutical composition will depend on absorption, inactivation and excretion rates of the active compound, dosing schedule and amount administered, and other factors known to those skilled in the art.

The active ingredient may be administered in a single dose, or may be divided into several smaller doses to be administered at intervals. It will be appreciated that the duration of treatment of an accurate dose is a function of the disease being treated and may be determined empirically using known test protocols or by extrapolation from in vivo or in vitro test data. It is noted that concentrations and dosage values may also vary depending on the severity of the condition to be alleviated. It will be further understood that for any particular subject, the specific dosage regimen will be adjusted over time according to the individual needs and the professional judgment of the person administering or monitoring the administration of the composition, and that the concentration ranges described herein are exemplary only and are not intended to limit the scope or practice of the claimed compositions.

If oral administration is desired, the compound should be provided in a composition that protects the compound from the gastric acid environment. For example, the composition may be formulated in an enteric coating which maintains its integrity in the stomach and releases the active compound in the intestine. The composition may be formulated in combination with an antacid or other such ingredient.

Oral compositions will generally include an inert diluent or an edible carrier and may be compressed into tablets or encapsulated in gelatin capsules. For the purpose of oral therapeutic administration, one or more active compounds may be combined with excipients and used in the form of tablets, capsules or lozenges. Pharmaceutically compatible binders and auxiliary materials may be included as part of the composition.

Tablets, pills, capsules, lozenges, and the like may contain any of the following ingredients or compounds of similar properties: binders such as, but not limited to, gum tragacanth, acacia, corn starch or gelatin; excipients, such as microcrystalline cellulose, starch or lactose; disintegrants such as, but not limited to, alginic acid and corn starch; lubricants such as, but not limited to, magnesium stearate; glidants such as, but not limited to, colloidal silicon dioxide; sweetening agents, such as sucrose or saccharin; and flavoring agents, such as peppermint, methyl salicylate, or fruit flavors.

When the dosage unit form is a capsule, it may contain, in addition to materials of the above type, a liquid carrier such as a fatty oil. In addition, dosage unit forms may contain various other materials which modify the physical form of the dosage unit, such as sugar coatings and other enteric coatings. The compounds may also be administered as components of elixirs, suspensions, syrups, wafers, chewing gums and the like. Syrups may contain, in addition to the active compound, sucrose as a sweetening agent, and certain preservatives, dyes, colorants and flavors.

The active ingredient may also be mixed with other active ingredients that do not impair the desired effect or supplement the desired effect.

Solutions or suspensions for parenteral, intradermal, subcutaneous or topical administration may include any of the following components: sterile diluents, such as water for injection, saline solution, fixed oils, naturally occurring vegetable oils such as sesame oil, coconut oil, peanut oil, cottonseed oil and the like, or synthetic fatty vehicles such as ethyl oleate and the like, polyethylene glycols, glycerol, propylene glycol or other synthetic solvents; antimicrobial agents, such as benzyl alcohol and methyl paraben; antioxidants such as ascorbic acid and sodium bisulfite; chelating agents, such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates and phosphates; and tonicity adjusting agents such as sodium chloride and dextrose. The parenteral formulations may be enclosed in ampoules, disposable syringes or multiple dose vials made of glass, plastic or other suitable material. A buffer, a preservative, an antioxidant and the like may be incorporated as necessary.

If administered intravenously, suitable carriers include physiological saline, Phosphate Buffered Saline (PBS), and solutions containing thickening and solubilizing agents such as glucose, polyethylene glycol, polypropylene glycol, and mixtures thereof. Liposomal suspensions, including tissue-targeting liposomes, may also be suitable as pharmaceutically acceptable carriers. They can be prepared according to known methods, for example as described in U.S. Pat. No.4,522,811.

The active compound may be formulated with a carrier that protects the compound from rapid elimination from the body, for example, a time release formulation or a coating. Such carriers include controlled release formulations such as, but not limited to, implants and microencapsulated delivery systems, and biodegradable, biocompatible polymers such as collagen, ethylene vinyl acetate, polyanhydrides, polyglycolic acid, polyorthoesters, polylactic acid, and the like. Methods for the preparation of such formulations are known to the person skilled in the art.

The compounds of the invention may be administered enterally or parenterally. When administered orally, the compounds of the present invention may be administered in conventional dosage forms for oral administration, as is well known to those skilled in the art. These dosage forms include conventional solid unit dosage tablets and capsules, as well as liquid dosage forms such as solutions, suspensions, and elixirs. When solid dosage forms are used, it is preferred that they be of the sustained release type, so that the compounds of the present invention need only be administered once or twice daily.

Oral dosage forms are administered to a patient 1, 2, 3 or 4 times per day. Preferably, the compounds of the present invention are administered three times or less per day, more preferably once or twice. Thus, it is preferred that the compounds of the present invention be administered in oral dosage forms. Preferably, whatever oral dosage form is used, it is designed to protect the compounds of the present invention from the gastric acid environment. Enteric coated tablets are well known to those skilled in the art. Additionally, capsules filled with pellets, each coated to protect against gastric acid, are also well known to those skilled in the art.

When administered orally, an amount of from about 0.1 mg/day to about 1,000 mg/day that is therapeutically effective to inhibit beta-secretase activity, inhibit a beta production, inhibit a beta deposition, or treat or prevent AD. Preferably, the oral dosage is from about 1 mg/day to about 100 mg/day. More preferably, the oral dosage is from about 5 mg/day to about 50 mg/day. It will be appreciated that although the patient may begin with a dose, the dose may vary over time depending on the patient's condition.

The compounds of the present invention may also be advantageously delivered in nanocrystal dispersion formulations. The preparation of such formulations is described, for example, in U.S. Pat. No.5,145,684. Nanocrystalline dispersions of HIV protease inhibitors and methods of their use are described in U.S. patent No.6,045,829. Nanocrystalline formulations typically provide greater bioavailability of the pharmaceutical compound.

The compounds of the invention may be administered parenterally, for example by IV, IM, depo-IM, SC or depo-SC. When administered parenterally, a therapeutically effective amount of about 0.5 to about 100mg per day, preferably about 5 to about 50mg per day should be delivered. When using the storage formulation for once a month or once every two weeks for injection, the dose should be from about 0.5 mg/day to about 50 mg/day, or from about 15mg to about 1,500mg per month. Due in part to the amnesia of Alzheimer's disease patients, it is preferred that the parenteral dosage form is a depo formulation.

The compounds of the invention may be administered sublingually. When administered sublingually, the compounds of the present invention should be administered one to four times per day, at dosages as described above for IM administration.

The compounds of the invention may be administered intranasally. When administered by this route, suitable dosage forms are nasal sprays or dry powders, as known to those skilled in the art. The intranasal doses of the compounds of the invention are as described above for IM administration.

The compounds of the invention may be administered intrathecally. When administered by this route, suitable dosage forms may be parenteral dosage forms known to those skilled in the art. Intrathecally administered doses of the compounds of the invention are as described above for IM administration.

The compounds of the invention may be administered topically. When administered by this route, suitable dosage forms are creams, ointments or patches. In view of the amount of the compound of the present invention to be administered, a patch is preferable. When administered topically, the dosage is from about 0.5 mg/day to about 200 mg/day. Two or more patches may be used, as the amount that can be delivered by a patch is limited. The number and size of the patches is not critical and it is important to deliver a therapeutically effective amount of a compound of the invention, as is known to those skilled in the art. The compounds of the invention may be administered rectally by means of suppositories, as is known to those skilled in the art. When administered as a suppository, the therapeutically effective amount is about 0.5mg to about 500 mg.

The compounds of the invention may be administered via implants, as is known to those skilled in the art. When the compounds of the present invention are administered as implants, therapeutically effective amounts are as described above with respect to depot administration.

Given the particular compound of the invention and the desired dosage form, one skilled in the art will know how to make and administer the appropriate dosage form.

In the same manner as described above, by means of the same route of administration, using the same pharmaceutical dosage form and the same dosing schedule, the compounds of the invention are useful for the prevention of diseases or the treatment of MCI (mild cognitive impairment) patients, for the prevention or delay of the onset of alzheimer's disease in patients who will progress from MCI to AD, for the treatment or prevention of down's syndrome, for the treatment of hereditary cerebral hemorrhage with amyloidosis of the dutch type, for the treatment of cerebral amyloid angiopathy and for the prevention of its potential consequences, namely single and recurrent cerebral lobe hemorrhage, for the treatment of other degenerative dementias, including dementia of mixed vascular and degenerative origin, dementia associated with parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration and diffuse lewy body type alzheimer's disease.

The compounds of the present invention may be used in combination with each other or with other therapeutic agents or methods for treating or preventing the above-listed conditions. Such reagents or methods include: acetylcholinesterase inhibitors, e.g. tacrine (tetrahydroaminoacridine, commercially available as COGNEX^_) Donepezil hydrochloride (commercially available as Aricept)^_) And rivastigmine (commercially available from Exelono)^_) (ii) a Gamma-secretase inhibitors; anti-inflammatory agents, such as cyclooxygenase II inhibitors; antioxidants, such as vitamin E and bilobalide; immunological methods, such as immunization with A β peptide or administration of anti-A β peptide antibodies; a statin; direct or indirect neurotropic agents, e.g. Cerebrolysin^_AIT-082(Emilieu, 2000, Arch. neurol.57: 454) and other neurotropic agents of the future.

In addition, the compounds of formula (AA), (I) or (X) may also be used with P-glycoprotein (P-gp) inhibitors. P-gp inhibitors and the use of such compounds are known to those skilled in the art. See, for example, cancer research, 53, 4595. sup. 4602(1993), clean. cancer Res., 2, 7-12(1996), cancer research, 56, 4171. sup. 4179(1996), International publications WO 99/64001 and WO 01/10387. Importantly, the blood level of the P-gp inhibitor is such that it acts to inhibit P-gp from lowering cerebral blood levels of the compound of formula (A). To this end, the P-gp inhibitor and the compound of formula (A) may be administered simultaneously, by the same or different routes of administration, or at different times. It is not the time of administration that is important, but that effective blood levels of the P-gp inhibitor are produced.

Suitable P-gp inhibitors include cyclosporin A, verapamil, tamoxifen, quinidine, vitamin E-TGPS, ritonavir, megestrol acetate, progesterone, rapamycin, 10, 11-methylene dibenzosuberane, phenothiazine, acridine derivatives, such as GF120918, FK506, VX-710, LY335979, PSC-833, GF-102,918, and other steroids. It is to be understood that additional agents will be found which have the same function and therefore achieve the same result; such compounds are also considered to be effective.

The P-gp inhibitor may be administered orally, parenterally (IV, IM, IM-depo, SQ, SQ-depo), topically, sublingually, rectally, intranasally, intrathecally, and by implantation.

A therapeutically effective amount of a P-gp inhibitor is from about 0.1 to about 300 mg/kg/day, preferably from about 0.1 to about 150mg/kg per day. It will be appreciated that although the patient may start with a dose, the dose may vary over time as the condition of the patient changes.

When administered orally, the P-gp inhibitor may be administered in conventional oral dosage forms, as is known to those skilled in the art. These dosage forms include common solid unit dosage forms such as tablets and capsules, as well as liquid dosage forms such as solutions, suspensions, and elixirs. When solid dosage forms are used, it is preferred that they are of the sustained release type, so that the P-gp inhibitor need only be administered once or twice daily. The oral dosage form is administered to the patient one to four times per day. Preferably, the P-gp inhibitor is administered three times or less per day, more preferably once or twice per day. Thus, it is preferred that a solid dosage form of the P-gp inhibitor is administered, and it is further preferred that the solid dosage form is in a sustained release form, allowing for dosing once or twice a day. Preferably, whatever dosage form is used, it is designed to protect the P-gp inhibitor from the gastric acid environment. Enteric coated tablets are well known to those skilled in the art. Additionally, capsules filled with pellets, each coated to protect against gastric acid, are also well known to those skilled in the art.

In addition, the P-gp inhibitor may be administered parenterally. When administered parenterally, they may be administered by IV, IM, depo-IM, SQ or depo-SQ.

The P-gp inhibitor may be administered sublingually. When administered sublingually, the P-gp inhibitor should be administered one to four times per day at the same dose as IM administration.

The P-gp inhibitor may be administered intranasally. When administered by this route, suitable dosage forms are nasal sprays or dry powders, as known to those skilled in the art. The intranasal dose of the P-gp inhibitor is the same as that for IM administration.

The P-gp inhibitor may be administered intrathecally. When administered by this route, suitable dosage forms may be parenteral dosage forms known to those skilled in the art.

The P-gp inhibitor may be administered topically. When administered by this route, suitable dosage forms are creams, ointments or patches. In view of the amount of the P-gp inhibitor to be administered, a patch is preferable. However, the amount that a patch can deliver is limited. Thus, two or more patches may be required. The number and size of the patches is not critical and it is important to deliver a therapeutically effective amount of a P-gp inhibitor, as is known to those skilled in the art.

The P-gp inhibitor may be administered rectally by means of suppositories, as is known to those skilled in the art.

The P-gp inhibitor can be administered by means of an implant, as is known to those skilled in the art.

There is nothing novel about the route of administration and the dosage form of administration of the P-gp inhibitor. Given a particular P-gp inhibitor and the desired dosage form, one skilled in the art will know how to prepare an appropriate P-gp inhibitor dosage form.

It will be apparent to those skilled in the art that the precise dose and frequency of administration will depend upon the particular compound of the invention being administered, the particular condition being treated, the severity of the condition being treated, the age, weight and general physical condition of the particular patient and other pharmaceutical treatments which the individual may take, as is well known to those skilled in the art.

Inhibition of APP cleavage

The compounds of the invention inhibit APP cleavage between Met595 and Asp596 or at the corresponding sites of different isoforms, for example APP751 or APP770 or mutants thereof (sometimes referred to as the "beta-secretase site") numbered according to the APP695 isoform or mutants thereof. Without wishing to be bound by a particular theory, inhibition of β -secretase activity is believed to inhibit the production of β amyloid peptide (a β). Inhibitory activity is demonstrated in a variety of inhibition assays in which cleavage of an APP substrate in the presence of β -secretase is assayed in the presence of an inhibitory compound under conditions generally sufficient to result in cleavage at the β -secretase cleavage site. The reduction of APP cleavage at the β -secretase cleavage site is associated with inhibitory activity compared to untreated or inactive controls. Assay systems are known which can be used to demonstrate the efficacy of the inhibitors of the compounds of the present invention. Representative assay systems are described, for example, in U.S. patent nos. 5,942,400, 5,744,346 and in the following examples.

The enzymatic activity of beta-secretase and the production of a beta can be assayed in vitro or in vivo using natural, mutated and/or synthetic APP substrates, natural, mutated and/or synthetic enzymes and test compounds. The assays may include primary or secondary cells expressing native, mutated and/or synthetic APP and enzymes, animal models expressing native APP and enzymes, or transgenic animal models that may utilize expression of substrates and enzymes. The detection of enzymatic activity may be an analysis of one or more cleavage products, such as an immunoassay, a fluorescent or colorimetric assay, HPLC, or other detection means. The inhibitory compounds were identified as those having the ability to reduce the amount of β -secretase cleavage product produced compared to a control in which β -secretase mediated cleavage in the reaction system was observed and measured in the absence of the inhibitory compound.

Beta-secretase

Various forms of β -secretase are known and can be used for the determination of enzyme activity and for the inhibition of enzyme activity. They include native, recombinant and synthetic forms of the enzyme. Human β -secretases are known as β -site APP cleaving enzymes (BACE), Asp2 and memapsin 2 and have been characterized, for example, in U.S. Pat. No.5,744,346, PCT patent application publications WO 98/22597, WO 00/03819, WO 01/23533 and WO 00/17369 and in literature publications (Hussain et al 1999, mol. cell. neurosci.14: 419. 427; Vassar et al 1999, Science 286: 735. 741; Yan et al 1999, Nature 402: 533. 537; Sinha et al 1999, Nature 40: 537. 540; and Lin et al 2000, PNAS USA 97: 1456. 1460). Synthetic forms of the enzyme have also been described (WO 98/22597 and WO 00/17369). The beta-secretase can be isolated and purified from human brain tissue, or can be produced in cells, such as mammalian cells expressing a recombinase.

Preferred rearrangement compounds are effective in inhibiting β -secretase activity by about 50% at concentrations less than 50 micromolar, preferably at concentrations of 10 micromolar or less, more preferably 1 micromolar or less, most preferably 10 nanomolar or less.

APP substrates

Assays demonstrating β -secretase mediated inhibition of APP cleavage can employ any known form of APP, including the 695 amino acid "normal" homotype, as by Kang et al, 1987, Nature 325: 733-6, and; 770 amino acid homomorphic forms, such as Kitaguchi et al, 1981, Nature 331: 530-532; and variants, such as Swedish mutant (KM670-1NL) (APP-SW), London mutant (V7176F) and others. See, for example, U.S. Pat. Nos. 5,766,846 and Hardy, 1992, Nature Genet.1: 233-234 review of known variant mutations. Additional useful substrates include binary amino acid modifications, such as APP-KK, APP fragments, as disclosed in WO 00/17369, and synthetic peptides containing a beta-secretase cleavage site, Wild Type (WT) or mutant, such as SW, as described in U.S. Pat. Nos. 5,942,400 and WO 00/03819.

The APP substrate contains the beta-secretase cleavage site (KM-DA or NL-DA) of APP, such as the complete APP peptide or variant, APP fragment, recombinant or synthetic APP, or fusion peptide. Preferably, the fusion peptide comprises a beta-secretase cleavage site fused to a peptide having a moiety that can be used in an enzymatic assay, e.g., having isolation and/or detection properties. Useful moieties may be epitopes for antibody binding, labels or other detection moieties, binding substrates, and the like.

Antibodies

Products characteristic of APP cleavage can be measured by immunoassay methods using various antibodies, such as Pirttila et al, 1999, neuro. 21-4 and U.S. patent No.5,612,486. Antibodies that can be used to detect a β include, for example, monoclonal antibody 6E10(Senetek, st. louis, MO), which specifically recognizes an epitope on amino acids 1-16 of a β peptide; antibodies 162 and 164 specific for human A β 1-40 and 1-42, respectively (New York State Institute for Basic Research, State Island, NY); and an antibody that recognizes the β -amyloid peptide junction, i.e., the site between residues 16 and 17, as described in U.S. patent No.5,593,846. Antibodies raised against the synthetic peptides 591-596 of APP and SW192 raised against 590-596 of the Swedish mutant can also be used for the immunoassay of APP and its cleavage products, as described in U.S. Pat. Nos. 5,604,102 and 5,721,130.

Measurement system

Assays for determining cleavage of APP at the cleavage site of β -secretase are well known in the art. Exemplary assays are described, for example, in U.S. Pat. Nos. 5,744,346 and 5,942,400 and in the examples below.

Cell-free assay

Exemplary assays that can be used to demonstrate the inhibitory activity of the compounds of the invention are described, for example, in WO00/17369, WO 00/03819, U.S. Pat. Nos. 5,942,400 and 5,744,346. Such assays can be performed in cell-free culture or cell culture using cells expressing a beta-secretase enzyme and an APP substrate having a beta-secretase cleavage site.

Incubating an APP substrate comprising a beta-secretase cleavage site for APP, such as the complete APP or a variant, an APP fragment or a recombinant or synthetic APP substrate comprising the amino acid sequence KM-DA or NL-DA, in the presence of beta-secretase, a fragment thereof or a synthetic or recombinant polypeptide variant having beta-secretase activity and effective to cleave the beta-secretase cleavage site of APP under incubation conditions suitable for enzymatic cleavage activity. Suitable substrates optionally include derivatives which may be fusion proteins or peptides, which contain the substrate peptide and modifications useful for facilitating purification or detection of the peptide or its beta-secretase cleavage product. Useful modifications include insertion of epitopes known to be useful for antibody binding; attachment of a label or detectable moiety; ligation of binding substrates, etc.

Suitable incubation conditions for cell-free in vitro assays include, for example: about 200 nanomolar to 10 micromolar of a substrate, about 10 to 200 picomolar of an enzyme, and about 0.1 nanomolar to 10 micromolar of an inhibitor compound in aqueous solution at a pH of about 4-7 and a temperature of about 37 ℃ for about 10 minutes to 3 hours. These incubation conditions are exemplary only and can be varied as desired, depending on the particular assay components and/or the desired measurement system. The optimization of the incubation conditions according to the particular assay components should be interpreted as the specific beta-secretase used and its optimal pH, any additional enzymes and/or labels that might be used in the assay, etc. Such optimization is routine and would not require additional experimental methods.

A useful assay employs a fusion peptide having Maltose Binding Protein (MBP) fused to the C-terminal 125 amino acid of APP-SW. The MBP moiety is captured on the assay substrate by an anti-MBP capture antibody. Incubating the captured fusion protein in the presence of beta-secretase enzyme results in cleavage of the substrate at the beta-secretase cleavage site. The assay for cleavage activity may be, for example, an immunoassay for the cleavage product. One such immunoassay detects unique epitopes exposed at the carboxy terminus of the cleaved fusion protein, for example using antibody SW 192. Such an assay is described, for example, in U.S. patent No.5,942,400.

Cell assay

A number of cell-based assays are available for assaying beta-secretase activity and/or processing of APP-released a β. Intracellular contact of an APP substrate with β -secretase, with or without an inhibitor of a compound of the present invention, can be used to demonstrate the β -secretase inhibitory activity of the compound. Preferably, the assay in the presence of the available inhibitory compounds provides at least about 30%, most preferably at least about 50% inhibition of enzyme activity compared to an uninhibited control.

In one embodiment, cells that naturally express beta-secretase are used. Alternatively, the cell is modified to express a recombinant β -secretase or a synthetic variant enzyme, as discussed above. The APP substrate may be added to the culture medium and preferably expressed in the cell. Cells that naturally express APP, APP variants or mutants, or cells transformed to express APP isoforms, APP mutants or variants, recombinant or synthetic APP, APP fragments, or synthetic APP peptides or fusion proteins containing a β -secretase APP cleavage site may be used, provided that the expressed APP is allowed to contact the enzyme and the cleavage activity of the enzyme can be assayed.

Human cell lines that normally process a β from APP provide an effective means to determine the inhibitory activity of the compounds of the invention. The production and release of a β and/or other lysate into the culture medium may be measured, for example, by means of an immunoassay, such as western blot or enzyme linked immunoassay (EIA), such as ELISA.

Cells expressing both the APP substrate and the active β -secretase can be cultured in the presence of the compound inhibitor to demonstrate inhibition of enzyme activity compared to a control. The activity of the β -secretase enzyme can be measured by assaying one or more cleavage products of the APP substrate. For example, inhibition of the activity of β -secretase on the substrate APP would be expected to reduce the release of specific β -secretase-induced cleavage products of APP, such as a β.

Although both neuronal and non-neuronal cells process and release a β, the level of endogenous β -secretase activity is low and is often difficult to detect by EIA. Thus, the use of cell types known to have enhanced β -secretase activity, enhanced processing of APP to a β, and/or enhanced a β production is preferred. For example, transfection of cells with Swedish mutant of APP (APP-SW), APP-KK or APP-SW-KK provides cells with enhanced β -secretase activity, wherein the amount of A β produced is readily measurable.

In such assays, for example, cells expressing APP and β -secretase are cultured in culture medium under conditions suitable for the β -secretase to exert activity on the APP substrate at its cleavage site. Upon exposure of the cells to the compound inhibitor, the amount of a β released into the medium and/or the content of CTF99 fragment of APP in the lysate (cell lysate) is reduced compared to the control. Cleavage products of APP can be analyzed, for example, by immunoreaction with specific antibodies, as discussed above.

Preferred cells for analysis of β -secretase activity include primary human neuronal cells, primary transgenic animal neuronal cells (where the transgene is APP), and other cells, such as those of the stable 293 cell line expressing APP, e.g., APP-SW.

In vivo assay: animal model

There are various animal models that can be used to assay β -secretase activity and/or processing of APP-released a β, as described above. For example, transgenic animals expressing an APP substrate and β -secretase can be used to demonstrate the inhibitory activity of the compounds of the invention. Certain transgenic animal models have been described, for example, in U.S. Pat. nos. 5,877,399; 5,612,486, respectively; 5,387,742, respectively; 5,720,936, respectively; 5,850,003, respectively; 5,877,015, respectively; and 5,811,633 and Ganes et al, 1995, Nature 373: 523. preferred are animals that exhibit characteristics associated with the pathophysiology of AD. Administration of the compound inhibitors of the invention to the transgenic mice described herein provides an alternative method of demonstrating the inhibitory activity of the compounds. It is also preferred that the compounds be administered in a pharmaceutically effective carrier via a route of administration that reaches the target tissue in a suitable therapeutic amount.

Inhibition of β -secretase mediated cleavage of APP at the β -secretase cleavage site and a β release can be assayed in these animals by measuring the cleavage fragments in animal fluids such as brain fluid or tissue. It is preferred to analyze brain tissue for a β deposits or plaques.

Upon contacting the APP substrate with the β -secretase enzyme in the presence of an inhibitory compound of the invention under conditions sufficient to allow enzyme-mediated cleavage of APP and/or release of A β from the substrate, the compound of the invention is effective to reduce β -secretase-mediated cleavage of APP at the β -secretase cleavage site and/or to reduce the amount of A β released. If such contact is administration of an inhibitory compound of the invention to an animal model, e.g., as described above, the compound is effective to reduce deposition of a β in brain tissue of the animal and to reduce the number and/or size of β amyloid plaques. If such administration is to a human subject, the compound is effective to inhibit or delay the progression of a disease characterized by increased amounts of A β, delay the progression of AD in the patient, and/or prevent the occurrence or development of AD in a patient at risk for the disease.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications mentioned herein are incorporated herein by reference.

Definition of

The following definitions and explanations pertain to the terms used throughout the specification, including the specification and claims.

It should be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a composition containing "a compound" includes a mixture of two or more compounds. It should also be noted that the term "or," when used, generally includes "and/or," unless expressly stated otherwise.

The symbol "-" generally represents a linkage between two atoms in a chain. Thus, CH₃-O-CH₂-CH(R_i)-CH₃Represents a 2-substituted-1-methoxypropane compound. In addition, the symbol "-" represents the point at which a substituent is attached to the compound. Thus, for example, aryl (C)₁-C₆) Alkyl-represents an alkylaryl group attached to the compound at the alkyl moiety, such as benzyl.

If multiple substituents are indicated as being attached to a structure, it is to be understood that the substituents may be the same or different. Thus, for example, "optionally substituted by 1, 2 or 3R_qRadical substituted R_m"represents R_mBy 1, 2 or 3R_qIs substituted by radicals in which R_qThe groups may be the same or different.

APP, amyloid precursor protein, is defined as any APP polypeptide, including APP variants, mutants, and isoforms, as disclosed, for example, in U.S. patent No.5,766,846.

A β, amyloid β peptide, is defined as any peptide resulting from β -secretase mediated cleavage of APP, including peptides of amino acids 39, 40, 41, 42 and 43, and extending from the β -secretase cleavage site to amino acids 39, 40, 41, 42 or 43.

Beta-secretase (BACE1, Asp2, Memapsin 2) is an aspartyl protease that mediates cleavage of APP at the amino-terminus of A β. Human beta-secretase is described, for example, in WO 00/17369.

Pharmaceutically acceptable means that the property and/or substance is acceptable to the patient from a pharmacological/toxicological point of view and to the manufacturing pharmaceutical chemist from a physical/chemical point of view with respect to composition, formulation, stability and patient acceptance.

A therapeutically effective amount is defined as an amount effective to reduce or attenuate at least one symptom of the disease being treated, or to reduce or delay the onset of one or more clinical markers or symptoms of the disease.

"alkyl" and "C₁-C₆Alkyl "in the present invention means a straight-chain or branched alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-hexyl and 3-methylpentyl. It is understood that where the alkyl chain of a substituent (e.g., alkyl, alkoxy, or alkenyl) is shorter or longer than 6 carbons, it will be represented in the second "C", e.g., C ₁-C₁₀Representing up to 10 carbons.

"alkoxy" and "C₁-C₆Alkoxy "in the present invention denotes a straight-chain or branched alkyl group having 1 to 6 carbon atoms, which is linked via at least one divalent oxygen atom, such as methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy and 3-methylpentyloxy.

The term "halogen" denotes in the present invention fluorine, bromine, chlorine and iodine.

"alkenyl" and "C₂-C₆Alkenyl "represents a straight or branched chain hydrocarbon group having 2 to 6 carbon atoms and 1 to 3 double bonds, and includes, for example, ethenyl, propenyl, 1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl, and the like.

"alkynyl" and "C₂-C₆Alkynyl "represents a straight or branched chain hydrocarbon group having 2 to 6 carbon atoms and 1 or 2 triple bonds, including ethynyl, propynyl, butynyl, pentyn-2-yl and the like.

The term "cycloalkyl" as used herein denotes a saturated carbocyclic group having from 3 to 12 carbon atoms. Cycloalkyl groups can be monocyclic, or a fused system of multiple rings. Examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Cycloalkyl groups herein are unsubstituted or, as indicated, substituted in one or more substitutable positions Various groups are substituted. For example, such cycloalkyl groups may optionally be substituted by C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C)₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl or di (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl substitution.

"aryl" means an aromatic carbocyclic group having a single ring (e.g., phenyl), multiple rings (e.g., biphenyl), or multiple fused rings, at least one of which is aromatic (e.g., 1, 2, 3, 4-tetrahydronaphthyl, naphthyl), which is optionally mono-, di-, or tri-substituted. Preferred aryl groups according to the invention are phenyl, 1-naphthyl, 2-naphthyl, indanyl, indenyl, dihydronaphthyl, tetrahydronaphthyl or 6, 7, 8, 9-tetrahydro-5H-benzo [ a ]]Cycloheptenyl. Aryl groups herein are unsubstituted or substituted as specified with various groups at one or more substitutable positions. For example, such aryl groups may optionally be substituted by, for example, C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C)₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C ₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, -COOH, -C (═ O) O (C)₁-C₆Alkyl), -C (═ O) NH₂-C (═ O) N (mono-or di-C)₁-C₆Alkyl), -S (C)₁-C₆Alkyl), -SO₂(C₁-C₆Alkyl), -O-C (═ O) (C)₁-C₆Alkyl), -NH-C (═ O) - (C)₁-C₆Alkyl), -N (C)₁-C₆Alkyl) -C (═ O) - (C)₁-C₆Alkyl), -NH-SO₂-(C₁-C₆Alkyl), -N (C)₁-C₆Alkyl) -SO₂-(C₁-C₆Alkyl), -NH-C (═ O) NH₂-NH-C (═ O) N (mono-or di-C)₁-C₆Alkyl), -NH (C)₁-C₆Alkyl) -C (═ O) -NH₂or-NH (C)₁-C₆Alkyl) -C (═ O) -N (mono-or di-C)₁-C₆Alkyl) substituted.

"heteroaryl" means one or more 5-, 6-, or 7-membered aromatic ring systems, including fused ring systems of 9 to 11 atoms, containing at least one, and up to four heteroatoms selected from nitrogen, oxygen, or sulfur. Preferred heteroaryl groups of the present invention include pyridyl, pyrimidinyl, quinolinyl, benzothienyl, indolyl, indolinyl, pyridazinyl, pyrazinyl, isoindolinyl, isoquinolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, furyl, thienyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isobenzodihydropyranyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuryl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridyl, A benzotetrahydrofuranyl group, a benzotetrahydrothienyl group, a purinyl group, a benzodioxolyl group, a triazinyl group, a phenoxazinyl group, a phenothiazinyl group, a pteridinyl group, a benzothiazolyl group, an imidazopyridinyl group, an imidazothiazolyl group, a dihydrobenzisoxazinyl group, a benzisoxazinyl group, a benzoxazinyl group, a dihydrobenzisothiazinyl group, a benzopyranyl group, a benzothiopyranyl group, a coumarinyl group, an isocoumarin group, a benzopyranonyl group, a chromanonenyl group, a benzodioxolyl group, a phenothiazinyl group, a naphthoyl group, a, pyridyl-N-oxide, tetrahydroquinolyl, dihydroquinolyl, dihydroquinolonyl, dihydroisoquinolinyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, cinnolinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S, S-dioxide. Heteroaryl groups herein are unsubstituted or, as indicated, substituted at one or more substitutable positions with various groups. For example, such heteroaryl groups may optionally be substituted by C ₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C)₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, -COOH, -C (═ O) O (C)₁-C₆Alkyl), -C (═ O) NH₂-C (═ O) N (mono-or di-C)₁-C₆Alkyl), -S (C)₁-C₆Alkyl), -SO₂(C₁-C₆Alkyl), -O-C (═ O) (C)₁-C₆Alkyl), -NH-C (═ O) - (C)₁-C₆Alkyl), -N (C)₁-C₆Alkyl) -C (═ O) - (C)₁-C₆Alkyl), -NH-SO₂-(C₁-C₆Alkyl), -N (C)₁-C₆Alkyl) -SO₂-(C₁-C₆Alkyl), -NH-C (═ O) NH₂-NH-C (═ O) N (mono-or di-C)₁-C₆Alkyl), -NH (C)₁-C₆Alkyl) -C (═ O) -NH₂or-NH (C)₁-C₆Alkyl) -C (═ O) -N (mono-or di-C)₁-C₆Alkyl) substituted.

"heterocycle", "heterocycloalkyl" or "heterocyclyl" means one or more 3-, 4-, 5-, 6-or 7-membered ring systems, including fused ring systems of 9 to 11 atoms, containing at least one, and up to four heteroatoms selected from nitrogen, oxygen or sulfur. Preferred heterocycles for use in the invention include morpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S, S-dioxide, piperazinyl, homopiperazinyl, pyrrolidinyl, pyrrolinyl, tetrahydropyranyl, piperidinyl, tetrahydrofuranyl, tetrahydrothienyl, homopiperidinyl, homomorpholinyl, homophosphorpholinyl S, S-dioxide, oxazolidinonyl, dihydropyrazolyl, dihydropyrrolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidyl, dihydrofuranyl, dihydropyranyl, azepanyl (azepanyl), diazepanyl, tetrahydrothienyl S-oxide, tetrahydrothienyl S, S-dioxide and thiomorpholinyl S-oxide. The heterocyclic groups herein may be unsubstituted or substituted as specified by various groups at one or more substitutable positions. For example, such heterocyclic groups may optionally be substituted by C ₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C)₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl or ═ O substitution.

All patents and publications mentioned herein are incorporated herein by reference.

The structures are named using Name Pro IUPAC naming software version 5.09, available from advanced chemical Development, inc., 90 advanced Street West, Toronto, Ontario, M5H3V9, Canada.

The invention will be better understood with reference to the following examples. These examples are illustrative of specific embodiments of the invention and are not intended to limit the scope of the invention.

Chemical examples

The following detailed examples describe how to prepare and/or perform various processes for various compounds of the present invention, which are to be construed as merely illustrative, and not limitative of the remainder of the disclosure in any way whatsoever. Those skilled in the art will be able to readily determine from these processes the appropriate changes with respect to the reactants and reaction conditions and techniques.

Preparation example 1 tert-butyl (1S) -3-bromo-1- (3, 5-difluorobenzyl) -2-oxopropylcarbamate (III)

N-methyl-morpholine (5.83ml, 53mmol, 1.05eq.) was added to a solution of (2S) -2- [ (tert-butoxycarbonyl) amino ] -3- (3, 5-difluorophenyl) propionic acid (II, 15g, 50mmol) in THF (100ml) and the reaction was cooled to-78 ℃. Isobutyl chloroformate (6.87ml, 53mmol, 1.05eq.) was added rapidly. The cooling bath was then removed and the mixture was stirred for 1 hour. The reaction was monitored by TLC to ensure completion of the reaction, then the mixture was filtered, washed with anhydrous THF (50ml) and kept cool at-20 ℃ in the filter flask.

A 500ml graduated cylinder containing diethyl ether (200ml) and aqueous potassium hydroxide (40%, 60ml) was placed in an ice-salt bath. 1-methyl-3-nitro-1-nitrosoguanidine (5.6g, 106mmol, 2.1eq.) was added slowly while stirring, with the temperature kept below zero. The mixture turned yellow and bubbling continued for 10 minutes. Stopping stirring, without mixing layers, transferring the top diazomethane ether layer to the stirring mixed acid with a non-polished tip pipette at-20 deg.CAnhydride mixtures. The reaction was monitored by TLC (EtOAc/hexane, 50/50; R)_f0.69). After 1 hour, nitrogen was bubbled through the mixture. The solvent was removed under reduced pressure (with heating) and the mixture was partitioned between ether and water. The phases were separated and the organic phase was washed with bicarbonate, brine, dried over anhydrous sodium sulfate, filtered and the solvent removed under reduced pressure (with heating). The residue was dissolved in ether (100ml), hydrobromic acid (48%, 15ml, 135mmol, 2.7eq.) was added at-20 ℃, the cooling bath was removed and the mixture was stirred for an additional half hour. The reaction was monitored by TLC (EtOAc/hexane, 50/50; R) _f0.88). The mixture was partitioned between ether and water, washed with bicarbonate, brine, dried over anhydrous sodium sulfate, filtered and the solvent removed. The residue was recrystallized from ethanol to give the title compound, TLC (ethyl acetate/hexane, 50/50) R_f＝0.88；MS(MH⁺)＝379.3。

Preparation example 2 tert-butyl (1S, 2S) -3-bromo-1- (3, 5-difluorobenzyl) -2-hydroxypropyl carbamate (IV)

Sodium borohydride (1.32g, 34.9mmol, 1.1eq.) was added to a solution of tert-butyl (1S) -3-bromo-1- (3, 5-difluorobenzyl) -2-oxopropylcarbamate (III, preparation 1, 12g, 31.75mmol) in absolute ethanol (500ml) at-78 ℃. The reaction mixture was stirred for 30 min and monitored by TLC (EtOAc/hexane, 20/80; R)_f0.2). The mixture was quenched with water (10ml) and the solvent removed under reduced pressure while heating (no more than 30 ℃) to dryness. The solid was partitioned between dichloromethane and water, washed with brine and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure to give the title compound, TLC (ethyl acetate/hexane, 20/80) R_f＝0.2；MS(MH⁺)＝381.2。

Preparation example 3 tert-butyl (1S) -2- (3, 5-difluorophenyl) -1- [ (2S) -oxiranyl ] ethylcarbamate (V)

Tert-butyl (1S, 2S) -3-bromo-1- (3, 5-difluorobenzyl) -2-hydroxypropyl carbamate (IV, preparation 2) was dissolved in absolute ethanol (150ml) and ethyl acetate (100ml), and hydroxide was added thereto at-20 deg.C Potassium (2.3g, 34.9mmol, 1.1eq.) in ethanol (85%, 5 ml). The cooling bath was then removed and the mixture was stirred for 30 minutes. The reaction was monitored by TLC (ethyl acetate/hexane, 20/80). When the reaction was complete, it was diluted with dichloromethane, extracted, washed with water, brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography on silica gel to give the title compound, TLC (ethyl acetate/hexane, 20/80) R_f＝0.3；MS(MH⁺)＝300.4。

Preparation example 4: tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -2-hydroxy-3- [ (3- (trifluoromethyl) benzyl) amino ] propylcarbamate

Tert-butyl (1S) -2- (3, 5-difluorophenyl) -1- [ (2S) -oxirane radical]Ethyl carbamate (preparation 3, 8.5g, 28.4mmol) was mixed with isopropanol (145 ml). To the reaction flask was added 3- (trifluoromethyl) benzylamine. The reaction mixture was heated to reflux for 3 hours and HPLC analysis indicated complete disappearance of the epoxide. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between ethyl acetate and aqueous hydrochloric acid. The organic phase was separated, washed with aqueous hydrochloric acid, bicarbonate and brine, and then dried over sodium sulfate. Concentrated under reduced pressure and recrystallized from hot hexane to give the title compound, MS (MH) ⁺)475。

Preparation example 5: tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -2-hydroxy-3- { (tert-butoxy) carbonyl-3- { (trifluoromethyl) benzyl } amino } propylcarbamate

To tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -2-hydroxy-3- [ (3- (trifluoromethyl) benzyl) amino at 0 deg.C]Propylcarbamate (preparation 4, 6.2g, 13.1mmol) in THF (70ml) was added dicarbonateTert-butyl ester (6.3g, 28.9 mmol). The reaction mixture was stirred at 20-25 ℃ for 18 hours. The reaction mixture was diluted with diethyl ether, washed with bicarbonate, 0.5M citric acid and brine, then dried over sodium sulfate and concentrated to give the title compound, MS (MNa)⁺)597。

Preparation example 6: 3-iodo-5- (methoxycarbonyl) benzoic acid

To an ice-cold, stirred solution of commercially available 3-amino-5- (methoxycarbonyl) benzoic acid (5.19g, 26.59mmol) in 2N hydrochloric acid (156ml) was added a solution of sodium nitrite (1.84g, 26.67mmol) in water (10.8 ml). The mixture was then added dropwise to an ice-cold, stirred solution of potassium iodide (8.84g, 53.25mmol) in water (26.2 ml). After stirring for 35 minutes, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with 5% aqueous sodium thiosulfate and saturated sodium chloride, dried (sodium sulfate), and concentrated under reduced pressure. Purification by flash column chromatography (silica, 50: 2 hexanes/ethyl acetate/acetic acid) gave the title compound (4.48g, 55% yield) as an off-white solid. ESI-MS (m/z): 305[ M + H ]⁺.

Preparation example 7: 3- [ (dipropylamino) carbonyl ] -5- (1, 3-oxazol-2-yl) benzoic acid

To a solution of oxazole (4.0g, 58mmol) in tetrahydrofuran (100ml) at-70 deg.C was added n-butyllithium (1.6M in hexane, 40ml, 64 mmol). After 30 min, zinc chloride (1M diethyl ether solution, 166ml, 166mmol) was added and the reaction mixture was warmed to 0 ℃ for 1 h. To the mixture was added 3-iodo-5- (methoxycarbonyl) benzoic acid (preparation 6, 21.4g, 55mmol) and tetrakis (triphenylphosphine) palladium (0) (2.7g, 2.34 mmol). The reaction mixture was heated at reflux for 1 hour. Subjecting the reaction mixture toEthyl acetate (300ml) was diluted and washed with water and saturated sodium chloride. The organic layer was dried (sodium sulfate) and concentrated under reduced pressure. Purification over a silica gel plug (10-33% ethyl acetate/hexanes) gave oxazole (17.7g, 97%) as a pale yellow solid:¹HNMR(300MHz，CDCl₃)δ8.73(t，J＝2Hz，1H)，8.24(t，J＝2Hz，1H)，8.11(t，J＝2Hz，1H)，7.77(d，J＝1Hz，1H)，7.28(d，J＝1Hz，1H)，3.97(s，3H)，3.49(m，2H)，3.19(m，2H)，1.71(m，2H)，1.57(m，2H)，1.01(m，3H)，0.76(m，3H)。

to a stirred solution of the ester of step 1 (17.7g, 53.6mmol) in tetrahydrofuran (50ml), methanol (25ml) and water (25ml) was added lithium hydroxide monohydrate (6.92g, 165 mmol). The reaction mixture was stirred at room temperature for 2 hours and then concentrated under reduced pressure. The residue was partitioned between water (100ml) and diethyl ether (100 ml). The aqueous layer was acidified to pH 4-5 with hydrochloric acid and extracted with ethyl acetate (3X 200 ml). The combined organic layers were washed with saturated sodium chloride, dried (sodium sulfate) and concentrated under reduced pressure to half the original volume. The resulting precipitate was collected by filtration and washed with hexane to give the title compound (15.5g, 91%) as an off-white solid: mp 131-; ¹H NMR(300MHz，CD₃OD)δ8.72(s，1H)，8.22(s，1H)，8.10(s，1H)，8.06(d，J＝1Hz，1H)，7.36(d，J＝1Hz，1H)，3.52(m，2H)，3.25(m，2H)，1.76(m，2H)，1.62(m，2H)，1.02(m，3H)，0.76(m，3H)；APCI MS m/z 317[M+H]⁺。

Preparation example 8: (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl ] amino } methyl) propyl 3- [ (dipropylamino) carbonyl ] -5- (1, 3-oxazol-2-yl) benzoate dihydrochloride

To a solution of tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -2-hydroxy-3- { (tert-butoxy) carbonyl-3- { (trifluoromethyl) benzyl } amino } propylcarbamate (preparation 5, 594mg, 1.0mmol) in DMF (2ml)Adding 3- [ (dipropylamino) carbonyl group]-5- (1, 3-oxazol-2-yl) benzoic acid (preparation 7, 316mg, 1.0mmol), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (210mg, 1.1mmol) and 4- (dimethylamino) pyridine (146mg, 1.2 mmol). After 36 hours, the reaction mixture was diluted with ethyl acetate, washed with bicarbonate (2X) and brine (4X), then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography on silica eluting with a gradient of ethyl acetate/hexane (20/80 to 50/50) to provide (1R, 2S) -2- [ (tert-butoxycarbonyl) amino group]-1- ({ (tert-butoxycarbonyl) [3- (trifluoromethyl) benzyl)]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoate, MS (MNa) ⁺)895。

Reacting (1R, 2S) -2- [ (tert-butoxycarbonyl) amino group]-1- ({ (tert-butoxycarbonyl) [3- (trifluoromethyl) benzyl)]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoate (482mg, 0.55mmol) was dissolved in hydrochloric acid/dioxane (4N, 3ml) and stirred at 20-25 ℃ for 1 hour. The solvent was then removed under reduced pressure to give the title compound, MS (MH)⁺)673。

Preparation example 9: n-1- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ] -5- (1, 3-oxazol-2-yl) -N-3-, N-3- — dipropyl-N-1- [3- (trifluoromethyl) benzyl ] -isophthalamide hydrochloride

To tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -2-hydroxy-3- [ (3- (trifluoromethyl) benzyl) amino]Propylcarbamate (preparation 4, 393mg, 0.83mmol) in DMF (2ml) was added 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid (preparation 7, 262mg, 0.83mmol), 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (175mg, 0.91mmol) and 4- (dimethylamino) pyridine (122mg, 1.0 mmol). After 18 hours, the reaction mixture was diluted with ethyl acetate,washed with bicarbonate (2X) and brine (4X), then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography on silica gel eluting with a gradient of ethyl acetate/hexane (50/50 to 70/30) to give tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -3- { [3- [ (dipropylamino) carbonyl ] amino ]-5- (1, 3-oxazol-2-yl) benzoyl][3- (trifluoromethyl) benzyl group]Amino } -2-hydroxypropyl carbamate, MS (MH)⁺)773。

Tert-butyl (1S, 2R) -1- (3, 5-difluorobenzyl) -3- { [3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoyl][3- (trifluoromethyl) benzyl group]Amino } -2-hydroxypropyl carbamate (226mg, 0.29mmol) was dissolved in hydrochloric acid/dioxane (4N, 2ml) and stirred at 20-25 ℃ for 20 minutes. The solvent was then removed under reduced pressure and the crude product was purified by reverse phase HPLC eluting with a gradient solvent of acetonitrile/water containing 0.5% trifluoroacetic acid. The resulting trifluoroacetate salt was converted to the hydrochloride salt by treatment with a solution of HCl in methanol (1.25M, 5 ml). Concentration under reduced pressure gave the title compound, MS (MH)⁺)673。

The following compounds are prepared essentially following the procedures described in the reaction schemes, tables, examples and preparations described herein.

76	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester
76		78	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ cyclohexyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester
80	(1R, 2S) -2-amino-1- ({ [3- (cyclopropylamino) benzyl]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate	78
80		82	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
84	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester	82
84		86	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (piperazin-1-ylsulfonyl) benzoate dihydrochloride
88	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-iodophenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	86
88		90	(1R, 2S) -2-amino-1- { [ (3-sec-butylbenzyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
92	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (3-methylisoxazol-4-yl) benzoic acid ester hydrochloride	90
92		94	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-isobutylisoxazol-5-yl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester
96	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester	94
96		98	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- [ (dipropylamino) carbonyl]-6-methylisonicotinic acid ester
100	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (cyclopropylmethyl) (propyl) amino]Carbonyl } -5-methylbenzoic acid ester	98
100		102	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester
104	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-(1，3-oxazol-2-yl) benzoates	102
104		106	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (aminosulfonyl) -5- [ (dipropylamino) carbonyl ]Benzoic acid esters
108	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (1Z) -prop-1-en-1-yl)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	106

110	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1H-pyrazol-4-yl) benzoic acid ester hydrochloride
110		112	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) -1-methylethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate
114	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	112
114		116	(1R, 2S) -1- { [ (3-allylbenzyl) amino]Methyl } -2-amino-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
118	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	116
118		120	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) -1-methylethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl ]-5- (1, 3-oxazol-2-yl) benzoic acid ester
122	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ ethyl (propyl) amino]Carbonyl } -5-methylbenzoic acid ester	120
122		124	(1R, 2S) -2-amino-1- ({ [3- (cyclopropylamino) benzyl]Amino } methyl) -3- (3, 5-difluorobenzeneYl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
126	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate	124
126		128	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-isobutylisoxazol-5-yl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
130	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (5-formyl-4-methyl-2-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	128
130		132	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-isopropylbenzyl) amino]Methyl } propyl 5- [ (dipropylamino) carbonyl]Nicotinic acid esters
134	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (methylsulfonyl) amino group)]Benzyl } amino) methyl ]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	132
134		136	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (butylamino) carbonyl]-5-methylbenzoic acid ester
138	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3-methylbutyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	136
138		140	(1R, 2S) -2-amino-1- { [ (biphenyl-3-ylmethyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
142	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	140

194	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (ethylsulfonyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
194		196	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-chloro-2-thienyl) sulfonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine ester hydrochloride
198	(1R, 2S) -1- ({ [3- (5-acetyl-2-thienyl) benzyl]Amino } methyl) -2-amino-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester	196
198		200	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (sec-butylamino) carbonyl]-5-methylbenzoic acid ester
202	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1, 3-oxazol-2-yl) benzoate hydrochloride	200
202		204	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (2-phenylethyl) amino]Carbonyl benzoate ester
206	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3, 5-dimethylisoxazol-4-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	204
206		208	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (prop-2-yn-1-yl) amino]Carbonyl benzoate ester
210	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ ethyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester	208
210		212	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3- { [ (dimethylamino) carbonyl]Oxy } benzyl) amino]Methyl } propyl 3- (dipropylamino) carbonyl]-5-methylbenzoic acid ester
214	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl radical]Propyl 3- { [ benzyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester	212
214		216	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ sec-butyl (propyl) amino]Carbonyl } -5-methylbenzoic acid ester
218	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (4-methyl-2-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	216
218		220	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (methoxycarbonyl) (methyl) amino group]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
222	(1R, 2S) -2-amino-1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) -3- (2, 3, 5-trifluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	220
222		224	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (diisobutylamino) carbonyl]-5-methylbenzoic acid ester
226	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (2-pyridin-2-ylethyl) amino]Carbonyl benzoate ester	224

254	4- [ ((1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl) oxy]-4-oxo-3- { [ (1-propylbutyl) sulfonyl]Trifluoroacetic acid methyl ester
254		256	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ methyl (methylsulfonyl) amino]Benzoic acid esters
25	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2-hydroxyethyl) amino]Sulfonyl } -N ', N' -dipropyl-isophthalamide	256
25		27	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- [ (2-isobutyl-1, 3-thiazol-5-yl) methyl]-N ', N' -dipropyl-isophthalamide
29	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- (3-isopropylbenzyl) -N ', N' -dipropyl-isophthalamide	27
29		31	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-isopropylbenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-isophthalamide
33	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2-hydroxy-1, 1-dimethylethyl) amino ]Sulfonyl } -N ', N' -dipropyl-isophthalamide	31
33		35	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N-(3-Ethylbenzyl) -5- (4-methyl-1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide
37	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (2-isobutyl-1, 3-thiazol-5-yl) methyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide	35
37		39	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (3-hydroxypropyl) amino]Sulfonyl } -N ', N' -dipropyl-isophthalamide hydrochloride
41	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- (3-propylbenzyl) isophthalamide	39
41		43	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-butyl-N- (3-ethylbenzyl) -N', 5-dimethyl isophthalamide
45	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- (3-ethynylbenzyl) -N ', N' -dipropyl-isophthalamide	43
45		47	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- [ (3-isobutylisoxazol-5-yl) methyl ]-N ', N' -dipropyl-isophthalamide
49	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- [ (dimethylamino) sulfonyl group]-N- (3-ethylbenzyl) -N ', N' -dipropyl-isophthalamide	47
49		51	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide hydrochloride
53	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (5-formyl-2-thienyl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide	51

55	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-bromo-N- (3-iodobenzyl) -N ', N' -dipropyl-m-phenylenediAmides of carboxylic acids
55		57	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- ({ [ (1R) -2-hydroxy-1-methylethyl]Amino } sulfonyl) -N ', N' -dipropyl isophthalamide
59	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-isobutylbenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide	57
59		61	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl ]M-phenylene diamide
63	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2R) -2- (methoxymethyl) pyrrolidin-1-yl]Carbonyl } -5-methylbenzamide hydrochloride	61
63		65	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- ({ [ (1S) -2-hydroxy-1-methylethyl)]Amino } sulfonyl) -N ', N' -dipropyl isophthalamide
67	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-butyl-N- (3-ethylbenzyl) -5-methyl-N' -propyl-isophthalamide	65
67		69	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N ', N' -dibutyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide
71	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (3-hydroxyprop-1-yn-1-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide	69
71		73	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2S) -2- (hydroxymethyl) pyrrolidin-1-yl]Sulfonyl } -N ', N' -dipropyl-isophthalamide
75	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-butyl-N' -ethyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide	73
75		77	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxyButyl radical]-N- (3-ethynylbenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-isophthalamide
79	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-cyclohexyl-N- (3-ethylbenzyl) -N', 5-dimethyl-isophthalamide	77
79		81	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (cyclopropylamino) benzyl]-5-ethynyl-N ', N' -dipropyl-isophthalamide
83	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- [3- (3-thienyl) benzyl]M-phenylene diamide	81
83		85	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide

129	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-isobutylisoxazol-5-yl) cyclopropyl]-5-methyl-N ', N' -dipropyl-isophthalamide
129		131	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (5-formyl-4-methyl-2-thienyl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide
133	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-isopropylbenzyl) -N ', N' -dipropylpyridine-3, 5-dicarboxamide	131
133		135	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- {3- [ (methylsulfonyl) amino group]Benzyl } -N ', N' -dipropyl-isophthalamide
137	N-[(2R，3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' -butyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide	135
137		139	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [3- (3-methylbutyl) benzyl]-N ', N' -dipropyl-isophthalamide
141	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (biphenyl-3-ylmethyl) -5-methyl-N ', N' -dipropyl-isophthalamide	139
141		143	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethynylphenyl) cyclopropyl]-5-methyl-N ', N' -dipropyl-isophthalamide
145	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- ({ [2- (methylamino) ethyl)]Amino } sulfonyl) -N ', N' -dipropyl isophthalamide hydrochloride	143
145		147	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-5-ethynyl-N- [1- (3-isobutylisoxazol-5-yl) cyclopropyl]-N ', N' -dipropyl-isophthalamide
149	N, N-diallyl-N' - [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (3-ethylbenzyl) -5-methyl-m-phenylenediamine	147
149		151	N- [ (2R, 3R) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (2-isobutyl-1, 3-thiazol-5-yl) cyclopropyl ] amine]-5-methyl-N ', N' -dipropyl-isophthalamide
153	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethylphenyl) -1-methylethyl]-5-methyl-N ', N' -dipropyl-isophthalamide	151
153		155	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2-hydroxyethyl) amino]Sulfonyl } -N' -propyl-isophthalamide
157	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' -propylisophthalamide	155
157		159	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride
161	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N ', N' -diethyl-N- (3-ethylbenzyl) -5- (1, 3-oxazol-2-yl) isophthalamide	159

205	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' - (2-phenylethyl) isophthalamide
205		207	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (3, 5-dimethylisoxazol-4-yl) benzyl]-5-methyl group-N ', N' -dipropyl-isophthalamide
209	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' -prop-2-yn-1-yl-isophthalamide	207
209		211	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-Ethyl-N- (3-ethylbenzyl) -N', 5-dimethyl isophthalamide
213	3- [ ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) methyl]Phenyl dimethyl carbamate	211
213		215	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-benzyl-N- (3-ethylbenzyl) -N', 5-dimethyl-isophthalamide
217	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '- (sec-butyl) -N- (3-ethylbenzyl) -5-methyl-N' -propyl isophthalamide	215
217		219	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [3- (4-methyl-2-thienyl) benzyl]-N ', N' -dipropyl-isophthalamide
221	{3- [ ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) methyl]Phenyl } methyl carbamate	219
221		223	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2, 3, 5-trifluorophenyl) butyl]-5-methyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide
225	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', N' -diisobutyl-5-methylisophthalimide	223
225		227	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' - (2-pyridin-2-ylethyl) isophthalamide
229	N- [ (2R, 3S) -3-amino-4- (3-fluoro-5-hydroxyphenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamideHydrochloride salt	227
229		231	N¹- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide
233	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-4-hydroxy-N- (3-iodobenzyl) -3- (pyrrolidin-1-ylcarbonyl) benzamide	231
233		235	5-oxo-D-prolyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride

278	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (1-methylhexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
278		280	(1R, 2S) -2-amino-1- ({ [1- (aminocarbonyl) cyclohexyl)]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
282	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2E) -hex-2-en-1-ylamino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	280
282		284	(1R, 2S) -2-amino-3- (4-fluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
286	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-hydroxyisoxazole-5-carboxylate	284
286		288	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (1E) -hex-1-en-1-yl)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
290	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (isopropylamino) carbonyl]-5-methylbenzoic acid ester	288
290		292	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (2-thienyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
294	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl [3- (2-amino-2-oxoethoxy) phenyl]Acetic acid ester	292
294		296	(1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
298	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2-ethylhexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	296
298		300	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (6-methoxypyridin-3-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
302	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (2, 4-dimethoxypyrimidin-5-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	300
302		304	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (2-ethylbutanoyl) benzoate
306	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (4-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzoic acid ester	304
306		308	(1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
310	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 4- [ 2' - (aminocarbonyl) biphenyl-4-yl]-4-oxobutanoic acid ester	308

289	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- {3- [ (1E) -hex-1-en-1-yl]Benzyl } -5-methyl-N ', N' -dipropyl-isophthalamide
289		291	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -isopropyl-5-methyl-isophthalamide
293	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	291
293		295	2- (3- {2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-iodobenzyl) amino]-2-oxoethyl } phenoxy) acetamide
297	N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl ]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide	295
297		299	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2-ethylhexyl) -5-methyl-N ', N' -dipropyl-isophthalamide
301	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (6-methoxypyridin-3-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide	299
301		303	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (2, 4-dimethoxypyrimidin-5-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide
305	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (2-ethylbutyryl) benzamide	303
305		307	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (4-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzamide
309	N¹- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	307
309		311	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 4- [ 2' - (aminocarbonyl) biphenyl-4-yl]-4-oxobutanoic acid ester
313	1- (3- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ](3-ethylbenzyl) amino]Carbonyl } -5-methylbenzoyl) -L-prolinamide	311
313		315	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (3-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzamide
317	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-hydroxy-1-phenylpropyl) -5-methyl-N ', N' -dipropyl isophthalamide	315
317		319	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [2- (dimethylamino) ethyl group]-N-ethyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide
321	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-methyl-4H, 6H-pyrrolo [1, 2-a)][4，1]Benzoxazepine-4-carboxamides	319

345	N¹- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide
345		347	N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide
349	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-cyclohexyl-N' -ethyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide	347
349		351	2- ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) ethyl (2, 4-difluorophenyl) carbamate
353	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2S) -2- (methoxymethyl) pyrrolidin-1-yl]Carbonyl } -5-methyl groupBenzamide hydrochloride	351
353		355	N¹- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide
357	N¹- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	355
357		359	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 8-dimethylquinoline-3-carboxamide
361	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (6-hydroxyhexyl) -5-methyl-N ', N' -dipropyl-isophthalamide	359
361		363	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (2R) -2-hydroxypropyl]-5-methyl-N ', N' -dipropyl-isophthalamide
365	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -3- [ (1-propylbutyl) sulfonyl]Propionamide	363
365		367	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -3- { [ (2-hydroxy-1, 1-dimethylethyl) amino]Sulfonyl benzamide
369	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (4-phenylbutyl) -N ', N' -dipropyl-isophthalamide	367
369		371	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-7- (1H-imidazol-1-yl) -N- (3-iodobenzyl) -5, 6-dihydronaphthalene-2-carboxamide
373	3- (acetylamino) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-methylbenzamide	371
373		375	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [2- (aminosulfonyl) ethyl]-5-methyl-N ', N' -dipropyl-isophthalamide
377	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [2- (ethylthio) ethyl]-5-methyl-N ', N' -dipropyl-isophthalamide	375

484	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4- { [2- (trifluoromethyl) phenyl]Amino butyrate
484		486	(1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
488	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 4, 5-dimethyl-2- (1H-pyrrol-1-yl) thiophene-3-carboxylate	486
488		490	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2, 3-dihydroxypropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
492	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (2S) -2-hydroxypropyl { (2S))]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	490
492		494	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -1-methylpropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
496	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-chloro-4- (methylsulfonyl) benzoate	494
496		498	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2-hydroxyethyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
500	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (3-methoxyphenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	498
500		502	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { methyl [ (trifluoromethyl) sulfonyl group]Amino benzoate hydrochloride
504	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-hydroxy-6- (1-hydroxy-2, 2-dimethylpropyl) pyridine-2-carboxylate	502
504		506	(1R, 2S) -2-amino-1- { [ (1, 3-dicyclohexylpropyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
508	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl radicalPropyl 2, 2' -bithiophene-5-carboxylate	506
508		510	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1H-imidazol-1-yl) butanoic acid ester
512	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 3-dihydroxy-4- [ (4-methoxyphenyl) amino]-4-oxobutanoic acid ester	510
512		514	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-hydroxyphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
516	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	514

518	(1R, 2S) -2-amino-1- [ (benzylamino) methyl group]-3- (2-thienyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl ]Benzoic acid esters
518		520	(1R, 2S) -2-amino-1- ({ [2- (aminocarbonyl) -1H-indol-6-yl]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
522	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-bromophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	520
522		524	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [4- (trifluoromethyl) benzoyl]Glycine ester
526	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1-oxo-1, 3-dihydro-2H-isoindol-2-yl) butanoate	524
526		528	(1R, 2S) -2-amino-3- (3, 5-fluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3, 4-dichlorobenzoyl) glycine ester
530	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-chloro-4- (methylsulfonyl) thiophene-2-carboxylate	528
530		532	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (1-ethylpropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
534	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({ [ (5R) -3-ethyl-2-oxo-1, 3-oxazolidin-5-yl) ]Methyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	532
534		536	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methyl-7- (trifluoromethyl) pyrazolo [1, 5-a]Pyrimidine-2-carboxylic acid esters
538	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (methylthio) acetyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine ester hydrochloride	536
538		540	(1R, 2S) -2-amino-3- (3, 5-bis)Fluorophenyl) -1- { [ (2, 3-dimethylcyclohexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
542	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4, 5-dimethoxy-1-benzothiophene-2-carboxylate	540
542		544	(1R, 2S) -2-amino-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
546	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({ [ (5S) -3-ethyl-2-oxo-1, 3-oxazolidin-5-yl)]Methyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	544
546		548	(1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methoxybenzyl) amino ]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
550	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 5-dioxo-1, 2, 4-triazolidin-4-yl) benzoate	548

574	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate
574		576	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [ (trifluoromethyl) sulfonyl]Amino } butanoate trifluoroacetate salt
578	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (5-methyl-1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) acetate	576
578		580	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-hydroxypropyl) amino]Methyl } propane3- [ (dipropylamino) carbonyl group]-5-methylbenzoic acid ester
582	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (hydroxymethyl) propyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	580
582		584	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3, 5-dichlorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl ]Benzoic acid esters
586	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- { [ (2-hydroxyethyl) (propyl) amino]Sulfonyl propionate hydrochloride	584
586		588	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 5- (benzylthio) nicotinate
590	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1H-pyrazole-5-carboxylate	588
590		592	(1R, 2S) -2-AmmoniaPhenyl-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-chloro-3-methyl-2-oxo-2, 3-dihydro-1, 3-benzoxazole-5-carboxylate
594	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1H-benzimidazole-2-carboxylate	592
594		596	(1R, 2S) -2-amino-3-cyclohexyl-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
598	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-hydroxy-4, 7-dimethoxy-1-benzofuran-5-carboxylate	596
598		600	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (4-methylcyclohexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester
602	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl [1, 2, 4 ]]Triazolo [4, 3-a]6-Pyridinecarboxylic acid ester	600
602		604	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4-oxo-4- (2-thienyl) butanoic acid ester
606	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3, 5-dichlorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	604

581	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-hydroxypropyl) -5-methyl-N ', N' -dipropyl isophthalamide
581		583	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (hydroxymethyl) propyl]-5-methyl-N ', N' -dipropyl-isophthalamide
585	N¹- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl ] -butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	583
585		587	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- { [ (2-hydroxyethyl) (propyl) amino]Sulfonyl } -N- (3-methoxybenzyl) propanamide hydrochloride
589	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (benzylsulfanyl) -N- (3-ethylbenzyl) nicotinamide	587
589		591	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1H-pyrazole-5-carboxamide
593	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-chloro-N- (3-ethylbenzyl) -3-methyl-2-oxo-2, 3-dihydro-1, 3-benzoxazole-5-carboxamide	591
593		595	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1H-benzimidazole-2-carboxamide
597	N¹- [ (2R, 3S) -3-amino-4-cyclohexyl-2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	595
597		599	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -6-hydroxy-4, 7-dimethoxy-1-benzofuran-5-carboxamide
601	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (4-methylcyclohexyl) -N ', N' -dipropyl-isophthalamide	599
601		603	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) [1, 2, 4 ]]Triazolo [4, 3-a]Pyridine-6-carboxamides
605	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4-oxo-4- (2-thienyl) butanamide	603
605		607	N- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl ]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide
609	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-hydroxy-5-methylphenyl) -4-oxobutanamide	607
609		611	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-phenoxybenzamide
613	4- [ (aminocarbonyl) amino group]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) benzamide	611

615	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1S) -1- (hydroxymethyl) -3- (methylthio) propyl group]-5-methyl-N ', N' -dipropyl-isophthalamide
615		617	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -7-hydroxy-4-oxochroman-2-carboxamide
619	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1S) -1- (hydroxymethyl) -3-methylbutyl]-5-methyl-N ', N' -dipropyl-isophthalamide	617
619		621	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -1- (hydroxymethyl) propyl group]-N ', N' -dipropyl-isophthalamide
623	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-5-methyl-N- (1-methyl-3-phenylpropyl) -N ', N' -dipropyl isophthalamide	621
623		624	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (2, 3-dihydro-1-benzofuran-5-yl) -1, 3-thiazole-4-carboxylate
626	(1R, 2S) -2-amino-3- [3- (benzyloxy) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	624
626		628	(1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
630	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl radical]Propyl 3-oxo-3- (pentylamino) propionate	628
630		632	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (trifluoromethoxy) benzoate
634	(1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	632
634		636	(1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
638	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate	636
638		640	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [4- (acetylamino) phenyl]Amino } -4-oxobutanoic acid esters
642	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1-cyanoethyl) benzoate	640
642		644	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4-, [ solution of (A) ](5-phenyl-1, 3, 4-thiadiazol-2-yl) amino]Butyric ester
646	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (trifluoromethoxy) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	644

648	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [2- (2-oxo-2-pyrrolidin-1-ylethoxy) phenyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
648		650	(1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
652	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl (1, 1-dioxotetrahydro-2-thienyl) acetate	650
652		654	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-chlorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
656	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-hex-1-yn-1-yl nicotinate	654
656		658	(1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
660	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methoxyisoxazole-5-carboxylic acid ester	658
660		662	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 3-dimethyl-1H-indole-7-carboxylate
664	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3-chlorophenyl) -2-hydroxy-4-oxobutanoate	662
664		666	(1R, 2S) -2-amino-3- (3-fluoro-4-methoxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
668	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (1-methyl-1H-indol-3-yl) (oxo) acetate	666
668		670	(1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
672	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (4-methylphenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	670
672		674	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-fluoro-4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
676	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [5- (4-methylphenyl) -2H-tetrazol-2-yl]Acetic acid ester	674
676		678	(1R, 2S) -2-amino-3- (3, 5-dichlorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
680	(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (2-thienyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	678

682	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methyl-3-phenylisoxazole-4-carboxylic acid ester
682		684	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-fluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
686	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl)) Amino group]Methyl } propyl N- [ (methylsulfonyl) acetyl]-N-pentyl glycinate	684
686		688	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (4-methoxybenzoyl) glycine ester
690	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2, 6-difluorobenzoyl) glycine ester	688
690		692	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1H-indol-3-yl) -4-oxobutanoate
694	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (5-benzyl-1, 3, 4-thiadiazol-2-yl) amino]-4-oxobutanoic acid ester	692
694		696	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3-fluoro-4-methoxyphenyl) -4-oxobutanoate
698	4- { [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2- ({3- [ (dipropylamino) carbonyl]-5-methylbenzoyl } oxy) butyl]Amino } piperidine-1-carboxylic acid ethyl ester	696
698		700	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2-fluorobenzoyl) -1H-pyrrole-2-carboxylate
702	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-chlorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	700
702		704	(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
706	(1R, 2S) -2-amino-3- (4-hydroxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	704
706		708	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (4-morpholin-4-ylphenyl) acetate
710	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethoxy) phenyl group]Propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	708
710		712	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ benzyl (1-cyclopropylethyl) amino]-4-oxobutanoic acid ester
714	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (2, 5-dimethylbenzoyl) -5-methylbenzoate	712

716	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (2-methoxy-5-methylphenyl) amino ]-4-oxobutanoic acid ester
716		718	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3)-ethylbenzyl) amino]Methyl } propyl (3-hydroxyphenyl) acetate
720	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ hydroxy (2-methylphenyl) methyl]-5-methylbenzoic acid ester	718
720		722	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 5- (ethylthio) nicotinate
724	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [4- (2-furoyl) piperazin-1-yl]-4-oxobutanoic acid ester	722
724		726	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-fluoro-4-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
728	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-oxoisoindoline-1-carboxylate	726
728		730	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (ethylthio) benzoate
732	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl thieno [2, 3-b]Quinoline-2-carboxylic acid esters	730
732		734	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (4-methyl-1, 3-oxazol-2-yl) benzoate hydrochloride
736	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-fluorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	734
736		738	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- [ 2-furoyl (methyl) amino group]Benzoic acid esters
740	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4- (3-methoxyphenyl) -4-oxobutanoate	738
740		742	(1R, 2S) -2-amino-1- [ (cycloheptylamino) methyl]-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
744	(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	742
744		746	(1R, 2S) -2-amino-3- (3-fluoro-5-hydroxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester hydrochloride
748	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-hydroxy-1H-indole-2-carboxylate	746

794	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 5- [ (2, 4-difluorophenyl) amino]-5-oxopentanoate ester
794		796	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- [ (4, 6-dimethylpyrimidin-2-yl) amino]-5-oxopentanoate ester
798	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (3-methoxybenzoyl) -5-methylbenzoate	796
798		800	(1R, 2S) -2-amino-3- [3- (benzyloxy) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
802	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-dichlorophenyl) -4-oxobutanoic acid ester	800
802		804	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [4- (methoxycarbonyl) phenyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
806	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- [ (4-acetylphenyl) amino]-5-oxopentanoate ester	804
806		808	(1R, 2S) -2-amino-3- [4- (benzyloxy) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
810	(1R, 2R) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (phenylthio) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	808
810		812	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- ({2- [ (methylamino) carbonyl group]Phenyl } thio) propanoates
814	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- [ (1-propylbutyl) thio]Propionic acid ester hydrochloride	812
814		816	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (4-ethoxyphenyl) amino]-4-oxobutanoic acid ester
818	(1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	816
818		820	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [2- ({ [ (3-methoxyphenyl) amino)]Carbonyl } oxy) ethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
625	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (2, 3-dihydro-1-benzofuran-5-yl) -N- (3-ethylbenzyl) -1, 3-thiazole-4-carboxamide	820
625		627	N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) phenyl ]-2-hydroxybutyl } -N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide
629	N-[(2R，3S)-3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide	627

631	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -pentylmalonamide
631		633	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (trifluoromethoxy) benzamide
635	N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide	633
635		637	N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide
639	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide	637
639		641	N' - [4- (acetylamino) phenyl]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) succinamide
643	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-3- (1-cyanoethyl) -N- (3-ethylbenzyl) benzamide	641
643		645	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - (5-phenyl-1, 3, 4-thiadiazol-2-yl) succinamide
647	N¹- (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	645
647		649	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [2- (2-oxo-2-pyrrolidin-1-ylethoxy) phenyl]-N ', N' -dipropyl-m-benzeneDiamides
651	N¹- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	649
651		653	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (1, 1-dioxotetrahydro-2-thienyl) -N- (3-ethylbenzyl) acetamide
655	N- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide	653
655		657	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-hex-1-yn-1-ylnicotinamide
659	N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide	657
659		661	N- [ (2R, 3S) -3-amino-4- (3, 5-bis)Fluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-methoxyisoxazole-5-carboxamides
663	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 3-dimethyl-1H-indole-7-carboxamide	661

725	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- [4- (2-furoyl) piperazin-1-yl]-4-oxobutanamide
725		727	N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide
729	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-oxoisoindoline-1-carboxylic acid amide	727
729		731	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (ethylsulfanyl) benzamide
733	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) thieno [2, 3-b]Quinoline-2-carboxamides	731
733		735	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (4-methyl-1, 3-oxazol-2-yl) benzamide hydrochloride
737	N¹- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl ]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	735
737		739	N- (2- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } phenyl) -N-methyl-2-furoamide
741	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4- (3-methoxyphenyl) -4-oxobutanamide	739
741		743	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N-cycloheptyl-5-methyl-N ', N' -dipropyl isophthalamide
745	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	743
745		747	N- [ (2R, 3S) -3-amino-4- (3-fluoro-5-hydroxyphenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propionamide hydrochloride
749	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-hydroxy-1H-indole-2-carboxamide	747
749		751	N- [ (2R, 3S) -3-amino-4- (3, 5-difluoro)Phenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 2-dimethylchroman-8-carboxamides
753	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-benzyl-N- (3-ethylbenzyl) pyrazine-2-carboxamide 4-oxide	751
753		755	2- ({ [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-methoxybenzyl) amino]Carbonyl } amino) -N, N-dipropylethanesulfonamide
757	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -1- (hydroxymethyl) -2-methylpropyl]-5-methyl-N ', N' -dipropyl-isophthalamide	755

791	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R, 2S) -1- (hydroxy)Methyl) -2-methylbutyl]-5-methyl-N ', N' -dipropyl-isophthalamide
791		793	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (phenoxymethyl) benzamide
795	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (2, 4-difluorophenyl) -N- (3-ethylbenzyl) glutaramide	793
795		797	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (4, 6-dimethylpyrimidin-2-yl) -N- (3-ethylbenzyl) glutaramide
799	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (3-methoxybenzoyl) -N- (3-methoxybenzyl) -5-methylbenzamide	797
799		801	N¹- { (2R, 3S) -3-amino-4- [3- (benzyloxy) phenyl]-2-hydroxybutyl } -N¹- (3-methoxybenzyl) -N ³，N³-dipropylbenzene-1, 3, 5-trimethylamide
803	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dichlorophenyl) -N- (3-ethylbenzyl) -4-oxobutanamide	801
803		805	4- { (2S, 3R) -2-amino-4- [ {3- [ (dipropylamino) carbonyl]-5-methylbenzoyl } (3-methoxybenzyl) amino]-3-hydroxybutyl } benzoic acid methyl ester
807	N' - (4-acetylphenyl) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) glutaramide	805
807		809	N- { (2R, 3S) -3-amino-4- [4- (benzyloxy) phenyl]-2-hydroxybutyl } -N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide
811	N- [ (2R, 3R) -3-amino-2-hydroxy-4- (phenylthio) butyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide	809
811		813	2- ({3- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-3-oxopropyl } thio) -N-methylbenzamide
815	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -3- [ (1-propylbutyl) thio]Propionamide hydrochloride	813
815		817	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (4-ethoxyphenyl) -N- (3-ethylbenzyl) succinamide
819	N¹- (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	817
819		821	2- ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) ethyl (3-methoxyphenyl) carbamate
822	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (benzyloxy) benzoate	821

824	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -2-hydroxy-1-methylethyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
824		826	(1R, 2S) -2-amino-3- (pentafluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
828	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (4-hydroxyphenyl) -4-oxobutanoate	826
828		830	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
832	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (piperidin-3-ylsulfonyl) benzoate dihydrochloride	830
832		834	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-chloro-4-hydroxyquinoline-2-carboxylate
836	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (2-thienyl) propyl 5- (dipropylamino) -5-oxopentanoate	834
836		838	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -4-methylpentyl 3- [ (dipropylamino) carbonyl group]-5-methylbenzoic acid ester
840	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (6-oxo-3-phenylpyridazin-1 (6H) -yl) acetate	838
840		842	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- {4- [ (methylsulfonyl) amino group]Phenyl } propanoate
844	(1R, 2S) -2-amino-3- (4-fluoro-3-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	842
844		846	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
848	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 3- (2-chlorophenoxy) propionate	846
848		850	(1R, 2S) -2-amino-3- (4-fluorophenyl) -1- { [ (3-methylbutyl) amino ]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
852	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (4-chlorobenzoyl) -D-alanine ester	850
852		854	(1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester hydrochloride
856	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (4-methylphenyl)) -4-oxobutanoic acid ester	854

884	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-difluorophenyl) -4-oxobutanoate
884		886	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2-naphthyl) -4-oxobutanoic acid ester
888	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4, 6-diethoxypyridine-2-carboxylate	886
888		890	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (5-methyl-1H-pyrrol-2-yl) -4-oxobutanoic acid ester
892	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- ({ [2- (methylamino) ethyl]Amino } sulfonyl) benzoate hydrochloride	890
892		894	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3-methyl-5- (4-methylbenzoyl) benzoate
896	(1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- [ (benzylamino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	894
896		898	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (piperazin-1-ylsulfonyl) benzoate hydrochloride
900	(1R, 2S) -2-amino-1- [ ({2- [4- (aminosulfonyl) phenyl)]Ethyl } amino) methyl]-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	898
900		902	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ 2-hydroxy-1- (hydroxymethyl) ethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
904	(1R, 2S) -2-amino-3- (4-fluoro-3-methylphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	902
904		906	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (3-oxo-2, 1-benzisothiazol-1 (3H) -yl) propanoate
908	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2, 6-dihydroxypyrimidin-4-yl) acetate	906
908		910	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 5- (dipropylamino) -5-oxopentanoate
912	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-hydroxyphenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	910
912		914	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-difluorophenyl) -2-methyl-4-oxobutanoate
916	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-5- [ (2-pyridin-2-ylethyl) amino]Valeric acid ester	914

918	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [2- (4-fluorophenyl) -1, 3-benzoxazol-5-yl]Acetic acid ester
918		920	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenylaminocarbonyl) glycinate
922	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl N- (2, 6-bis)Methoxybenzoyl) glycine ester	920
922		924	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1, 3-dithiane-2-yl) -3-furoate
926	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- [ 2-oxo-2- (propylamino) ethyl]Benzoic acid esters	924
926		928	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-bromophenyl) propyl 3- [ (dipropylamino) sulfonyl]Propionic acid ester
930	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 3- (2-fluorophenyl) propionate	928
930		932	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methylthiophene-2-carboxylate
934	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl)Amino group]Methyl } propyl [4- (benzyloxy) phenyl]Acetic acid ester	932
934		936	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl [ (5, 7-dimethyl [1, 2, 4 ]]Triazolo [4, 3-a]Pyrimidin-3-yl) thio groups]Acetic acid ester
938	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (1-acetyl-2, 3-dihydro-1H-indol-7-yl) amino]-4-oxobutanoic acid ester	936
938		940	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 5- [ (3-acetylphenyl) amino]-5-oxopentanoate ester
942	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4-chlorophenoxy) -2-hydroxypropionate	940
942		944	N³- [ (1S, 2R) -3- (benzylamino) -1- (3-fluoro-4-methoxybenzyl) -2-hydroxypropyl]-N¹，N¹-dipropylbenzene-1, 3, 5-trimethylamide
946	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	944
946		948	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1H-indole-7-carboxylate
950	(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (3-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	948

974	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (4-methyl-4H-1, 2, 4-triazol-3-yl) thio group](phenyl) acetic acid ester
974		976	(1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
978	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1, 3-benzothiazol-2-yl) butanoate	976
978		980	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (3-chloro-4-fluorophenyl) amino group]-4-oxobutanoic acid ester
982	(1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	980
982		984	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (2-oxo-2, 3-dihydroquinazolin-4-yl) thio group]Acetic acid ester
823	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (benzyloxy) -N- (3-ethylbenzyl) benzamide	984
823		825	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1S) -2-hydroxy-1-methylethyl]-5-methyl-N ', N' -dipropyl-isophthalamide
827	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (pentafluorophenyl) butyl]-5-methyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide	825
827		829	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (4-hydroxyphenyl) -4-oxobutanamide
831	N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide	829
831		833	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (piperidin-3-ylsulfonyl) benzamide dihydrochloride
835	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-chloro-N- (3-ethylbenzyl) -4-hydroxyquinoline-2-carboxamide	833
835		837	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide
839	N- [ (2R, 3S) -3-amino-2-hydroxy-5-methylhexyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide	837
839		841	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (6-oxo-3-phenylpyridazin-1 (6H) -yl) acetamide
843	N- (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- {4- [ (methylsulfonyl) amino]Phenyl propanamide	841

889	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4, 6-diethoxy-N- (3-ethylbenzyl) pyridine-2-carboxamide
889		891	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (5-methyl-1H-pyrrol-2-yl) -4-oxobutanamide
893	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -3- ({ [2- (methylamino) ethyl)]Amino } sulfonyl) benzamide hydrochloride	891
893		895	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -3-methyl-5- (4-methylbenzoyl) benzamide
897	N- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide	895
897		899	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (piperazin-1-ylsulfonyl) benzamide hydrochloride
901	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- {2- [4- (aminosulfonyl) phenyl]Ethyl } -5-methyl-N ', N' -dipropyl-isophthalamide	899
901		903	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ 2-hydroxy-1- (hydroxymethyl) ethyl]-5-methyl-N ', N' -dipropyl-isophthalamide
905	N¹- [ (2R, 3S) -3-amino-4- (4-fluoro-3-methylphenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	903
905		907	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (3-oxo-2, 1-benzisothiazol-1 (3H) -yl) propanamide
909	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (2, 6-dihydroxypyrimidin-4-yl) -N- (3-ethylbenzyl) acetamide	907
909		911	N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide
913	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-N-benzyl-3- [ (dipropylamino) sulfonyl group]Propionamide	911
913		915	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-difluorophenyl) -N- (3-ethylbenzyl) -2-methyl-4-oxobutanamide
917	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - (2-pyridin-2-ylethyl) glutaramide	915
917		919	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [2- (4-fluorophenyl) -1, 3-benzoxazol-5-yl]Acetamide
921	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- (phenylaminocarbonyl) -N¹- (3-ethylbenzyl) glycinamide	919

947	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide
947		949	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -1H-indole-7-carboxamide
951	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	949
951		953	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (1, 2, 3-thiadiazol-4-yl) benzamide
955	N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide	953
955		957	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide
959	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-5-methyl-N- (3-methylbutyl-N ', N' -dipropyl-isophthalamide	957
959		961	N- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide
963	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ 1-methyl-3- (methylthio) -1H-indol-2-yl]Acetamide	961
963		965	N- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl ]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide
967	2- ({2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-2-oxoethyl } thio) -N- [4- (1, 3-oxazol-5-yl) phenyl]Acetamide	965
967		969	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-furyl) -4-oxobutanamide
971	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (3-pyridin-2-yl-1, 2, 4-oxadiazol-5-yl) propanamide	969
971		973	2- [2- (acetylamino) -1, 3-thiazol-4-yl ] -2]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) acetamide
975	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (4-methyl-4H-1, 2, 4-triazol-3-yl) thio]-2-phenylacetamide	973
975		977	N- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl-1-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide
979	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (1, 3-benzothiazol-2-yl) -N- (3-ethylbenzyl) butanamide	977

981	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N' - (3-chloro-4-fluorophenyl) -N- (3-ethylbenzyl) succinamide
981		983	N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide
985	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (2-oxo-2, 3-dihydroquinazolin-4-yl) thio]Acetamide	983
985		986	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3-methyl-5- (2-methylbenzoyl) benzoate
988	(1R, 2S) -2-amino-3- (4-hydroxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 5- (dipropylamino) -5-oxopentanoate	986
988		990	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
992	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 4-propoxybenzoate	990
992		994	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1-methyl-1H-indole-2-formic acid esters
996	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-chloro-2- (3-methyl-4H-1, 2, 4-triazol-4-yl) benzoate	994
996		998	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-difluorophenyl) -2-methoxy-4-oxobutanoate
1000	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [3- (2-thienyl) -1H-pyrazol-1-yl]Acetic acid ester	998
1000		1002	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-phenylamino-5-oxopentanoate
1004	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2-thio-1, 3-benzothiazol-3 (2H) -yl) acetate	1002
1004		1006	(1R，2S) -2-amino-1- [ (benzylamino) methyl]-3-Cyclohexylpropyl 3- [ (dipropylamino) carbonyl 1-5-methylbenzoate
1008	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (4-methoxyphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	1006
1008		1010	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3-hydroxy-4-methylphenyl) acetate
1012	(1R, 2S) -2-amino-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	1010

1014	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 7-fluoro-4H-imidazo [5, 1-c][1，4]Benzoxazine-3-carboxylic acid esters
1014		1016	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-dihydro-2H-1, 5-benzodioxan-7-yl) -4-oxobutanoate
1018	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1-benzofuran-3-carboxylate	1016
1018		1020	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (3, 4-dichlorophenyl) amino group]-3-oxopropionic acid ester
1022	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	1020
1022		1024	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -2-hydroxy-1-methylethyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
1026	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	1024
1026		1028	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 5-oxo-5- (pyridin-3-ylamino) pentanoate
1030	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-methyl-4-oxo-4H-benzopyran-6-carboxylate	1028
1030		1032	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl ({2- [ (5-methylisoxazol-3-yl) amino]-2-oxoethyl } thio) acetate
1034	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (1H-imidazol-1-yl) propyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	1032
1034		1036	(1R, 2S) -2-amino-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
1038	(1R, 2S) -2-amino-3- (4-hydroxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	1036
1038		1040	(1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
1042	(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (2-thienyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester	1040
1042		1044	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 4- [ (2, 2-dimethylpropanoyl) amino]-2-hydroxybenzoates
1046	(1R, 2S) -2-amino-3- (3-methoxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	1044

1048	(1R, 2S) -2-amino-3- (4-fluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- { [ (3-methoxybenzyl) amino]Sulfonyl benzoate esters
1048		1050	(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
1052	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 6- (2-furoylamino) hexanoate	1050
1052		1054	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (1-phenyl-4, 5-dihydro-1H-tetrazol-5-yl) thio]Acetic acid ester
1056	(1S, 2S) -2-amino-3-phenyl-1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- { [ (3-methoxybenzyl) amino]Sulfonyl benzoate esters	1054
1056		1058	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethyl-)Radical benzyl) amino]Methyl } propyl 4- (3, 4-dihydro-2H-benzopyran-6-yl) -4-oxobutanoate
1060	(1R, 2S) -2-amino-3- (3-methoxyphenyl) -1- { [ (3-methylbutyl) amino ]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	1058
1060		1062	(1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 5- (dipropylamino) -5-oxopentanoate
1064	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl indolizine-2-carboxylate	1062
1064		1066	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (trifluoromethoxy) phenyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester
1068	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl nicotinate 1-oxide	1066
1068		1070	(1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester
1072	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl propyl [ (aminocarbonyl) oxy group]Acetic acid ester	1070
1072		1074	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 3-dihydro-1H-cyclopenta [ b]Quinoline-9-carboxylic acid esters
1076	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-1H-pyrazole-5-carboxylate	1074
1076		1078	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- (benzoylamino) pentanoate
1080	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (methoxymethyl) thio group]Benzoic acid esters	1078

1082	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1, 3-benzothiazol-2-yl) -3-methoxypropionate
1082		1084	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (methylamino) carbonyl]Amino } -3- (3-thienyl) propionic acid esters
1086	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-pyridin-2-ylthiophene-2-carboxylate	1084
1086		1088	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (benzyloxy) -5-fluorophenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
1090	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (5, 6-dimethyl-2, 4-dioxo-1, 2, 3, 4-tetrahydropyridinePyridin-3-yl) acetic acid esters	1088
1090		1092	(1R, 2S) -2-amino-3- (3-fluoro-4-methoxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester
1094	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-isobutyl-1, 3-dioxoisoindoline-5-carboxylate	1092
1094		1096	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- (acetylamino) -2-furoate
1098	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (4-methoxyphenyl) acetyl]Glycine ester	1096
1098		1100	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propylisoquinoline-4-carboxylate
1102	(1R, 2S) -2-amino-3- [3-(benzyloxy) phenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters	1100
1102		1104	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (4-hydroxy-3-methoxyphenyl) acetate
1106	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (4-phenyl-4H-1, 2, 4-triazol-3-yl) thio]Acetic acid ester	1104
1106		1108	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3, 5-dimethoxyphenyl) acetate
1110	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-methoxyphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	1108
1110		1112	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2-ethyl-4H- [1, 2, 4)]Triazolo [1, 5-a]Benzimidazol-4-yl) acetic acid esters
1114	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (2-furyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester	1112

1116	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 7-chloro-1-benzofuran-2-carboxylate
1116		1118	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) propionate
1120	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-oxo-2H-1, 3-benzoxazin-3 (4H) -yl) propionate	1118
1120		1122	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (pyrimidin-2-ylthio) acetate
1124	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [3- (aminocarbonyl) -4, 5, 6, 7-tetrahydro-1-benzothien-2-yl ]Amino } -4-oxobutanoic acid esters	1122
1124		1126	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (5-phenyl-1, 3, 4-oxadiazol-2-yl) thio]Acetic acid ester
1128	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl quinoline-6-carboxylic acid ester	1126
1128		1130	(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (2-furyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters
1132	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2, 3-dihydro-1, 4-benzodioxine-6-yl) -4-oxobutanoate	1130
1132		1134	(1R，2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1H-indol-3-yl) -1H-pyrazole-5-carboxylate
1136	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4- { [ (methylamino) thiocarbonyl (carbonothioyl)]Amino } benzoic acid ester	1134
1136		1138	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 6-chloronicotinate
1140	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3-hydroxyphenyl) -4-oxobutanoate	1138
1140		1142	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (phthalazin-1-ylthio) acetate
1144	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (1-oxidopyridin-2-yl) thio]Acetic acid ester	1142
1144		1146	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (acetylamino) -5-fluoro-1H-indole-2-carboxylate
1148	(1S, 2S) -2-amino-3-phenyl-1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- { [ (3-chlorobenzyl) amino]Sulfonyl benzoate esters	1146

1005	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (2-thioxo-1, 3-benzothiazol-3 (2H) -yl) acetamide
1005		1007	N- [ (2R, 3S) -3-amino-4-cyclohexyl-2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide
1009	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methoxyphenyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	1007
1009		1011	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (3-hydroxy-4-methylphenyl) acetamide
1013	N- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl ]-2-hydroxybutyl } -5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide	1011
1013		1015	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -7-fluoro-4H-imidazo [5, 1-c][1，4]Benzoxazine-3-carboxamides
1017	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dihydro-2H-1, 5-benzodioxan-7-yl) -N- (3-ethylbenzyl) -4-oxobutanamide	1015
1017		1019	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1-benzofuran-3-carboxamide
1021	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (3, 4-dichlorophenyl) -N- (3-ethylbenzyl) malonamide	1019
1021		1023	N¹- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide
1025	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -2-hydroxy-1-methylethyl]-5-methyl-N ', N' -dipropyl-isophthalamide	1023
1025		1027	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide
1029	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -N' -pyridin-3-ylglutaramide	1027
1029		1031	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-methyl-4-oxo-4H-benzopyran-6-carboxylate
1033	2- ({2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-2-oxoethyl } thio) -N- (5-methylisoxazol-3-yl) acetamide	1031
1033		1035	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (1H-imidazol-1-yl) propyl]-5-methyl-N ', N' -dipropyl-isophthalamide
1037	N- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide	1035

1039	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutan)Mesityl) propionamide
1039		1041	N- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide
1043	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide	1041
1043		1045	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-4- [ (2, 2-dimethylpropanoyl) amino]-N- (3-ethylbenzyl) -2-hydroxybenzamide
1047	N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide	1045
1047		1049	N- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-3- [ (3-methoxybenzyl) amino group]Sulfonyl } -N- [3- (trifluoromethyl) benzyl]Benzamide derivatives
1051	N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide	1049
1051		1053	N- {6- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-6-oxohexyl } -2-furoamide
1055	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (1-phenyl-4, 5-dihydro-1H-tetrazol-5-yl) thio]Acetamide	1053
1055		1057	N- [ (2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- { [ (3-methoxybenzyl) amino]Sulfonyl } -N- [3- (trifluoromethyl) benzyl]Benzamide derivatives
1059	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dihydro-2H-chromen-6-yl) -N- (3-ethylbenzyl) -4-oxobutanamide	1057
1059		1061	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl ]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide
1063	N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide	1061
1063		1065	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) indolizine-2-carboxamide
1067	N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide	1065
1067		1069	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) nicotinamide 1-oxide
1071	N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide	1069

1073	2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-iodobenzyl) amino]-2-oxoethylcarbamate
1073		1075	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 3-dihydro-1H-cyclopenta [ b]Quinoline-9-carboxamides
1077	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-methyl-1H-pyrazole-5-carboxamide	1075
1077		1079	N- {5- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ](3-ethylbenzyl) amino]-5-oxopentyl } benzamide
1081	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- [ (methoxymethyl) thio group]Benzamide derivatives	1079
1081		1083	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (1, 3-benzothiazol-2-yl) -N- (3-ethylbenzyl) -3-methoxypropionamide
1085	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (methylamino) carbonyl]Amino } -3- (3-thienyl) propanamides	1083
1085		1087	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-pyridin-2-ylthiophene-2-carboxamide
1089	N¹- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide	1087
1089		1091	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (5, 6-dimethyl-2, 4-oxo-1, 2, 3, 4-tetrahydropyridin-3-yl) -N- (3-ethylbenzyl) acetamide
1093	N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methoxyphenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide	1091
1093		1095	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -2-isobutyl-1, 3-dioxoisoindoline-5-carboxamide
1097	5- (acetylamino) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-furoamide	1095
1097		1099	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- [ (4-methoxyphenyl) acetyl]Glycine amides
1101	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) isoquinoline-4-carboxamide	1099
1101		1103	N¹- { (2R, 3S) -3-amino-4- (3- (benzyloxy) phenyl]-2-hydroxybutyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-triamide
1105	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (4-hydroxy-3-methoxyphenyl) acetamide	1103

1172	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfinyl) -N- (methoxycarbonyl) -D-alanine ester
1172		1174	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl S-butyl-N- (methoxycarbonyl) -D-cysteine ester
1176	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ 2 ](3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl ]-3- [ (4, 4, 4-trifluorobutyl) sulfonyl group]-D-alanine esters	1174
1176		1178	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (4, 4, 4-trifluorobutyl) sulfinyl group]-D-alanine esters
1180	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-S- (4, 4, 4-trifluorobutyl) -D-cysteine ester	1178
1180		1182	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester
1184	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (2, 2, 2-trifluoroethoxy) carbonyl]-D-alanine esters	1182
1184		1186	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (2-cyanoethoxy) carbonyl]-D-alanine esters
1188	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- { [ (3R) -pyrrolidin-3-yloxy]carbonyl-D-alanine esters	1186
1188		1190	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (butylsulfonyl) -N- { [ (3S) -tetrahydrofuran-3-yloxy]carbonyl-D-alanine esters
1192	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [2- (acetylamino) ethoxy]Carbonyl } -3- (butylsulfonyl) -D-alanine ester	1190
1192		1194	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (pyridin-3-ylmethoxy) carbonyl]-D-alanine esters
1196	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (pyridin-4-ylmethoxy) carbonyl]-D-alanine esters	1194
1196		1198	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester
1200	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- (butylsulfonyl) -N- [ (2-cyanoethoxy) carbonyl]-D-alanine esters	1198
1200		1202	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) -D-alanine ester
1204	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino ]Methyl } propyl 3- (butylsulfonyl) -N (methoxycarbonyl) -D-alanine ester	1202

1206	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- [ (2-cyanoethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1206		1208	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- { [2- (acetylamino) ethoxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1210	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- (methoxycarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1208
1210		1212	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1214	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [2- (diethylamino) -2-oxoethoxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1212
1214		1216	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (methoxycarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1218	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- (isopropoxycarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1216
1218		1220	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (cyclopropylmethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1222	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (allyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1220
1222		1224	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (2-cyanoethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1226	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [2- (acetylamino) ethoxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1224
1226		1228	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (pyridin-3-ylmethoxy) carbonyl]-D-alanine esters
1230	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (pyridin-4-ylmethoxy) carbonyl ]-D-alanine esters	1228
1230		1232	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- { [ (benzyloxy) carbonyl]Amino } -4- (methylsulfonyl) butanoic acid ester
1234	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) -D-alanine ester	1232
1234		1236	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) -L-alanine ester
1238	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -2-hydroxy-1-phenylethyl)]Amino } methyl group) Propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1236

1240	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -2-methoxy-1-phenylethyl]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1240		1242	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -2-methoxy-1-phenylethyl)]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1244	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl ]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1242
1244		1246	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (prop-2-yn-1-yloxy) carbonyl]-D-alanine esters
1248	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (2-methoxyethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1246
1248		1250	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [ (3R) -1-acetylpyrrolidin-3-yl]Oxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1252	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3S) -tetrahydrofuran-3-yloxy]carbonyl-D-alanine esters	1250
1252		1254	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3S) -tetrahydrofuran-3-yloxy]carbonyl-L-alanine esters
1256	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl ]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1254
1256		1258	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-L-alanine esters
1260	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1258
1260		1262	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1264	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1262
1264		1266	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1268	(1R, 2S) -2-amino-1- { [ (cyclopropylmethyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1266
1268		1270	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylphenyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl ]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters

1340	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (pyridin-3-ylcarbonyl) -D-alanine ester
1340		1342	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (2, 4-dimethyl-1, 3-thiazol-5-yl) carbonyl]-D-alanine esters
1344	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- { [3- (trifluoromethyl) -1H-pyrazol-4-yl]carbonyl-D-alanine esters	1342
1344		1346	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters
1348	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (1H-imidazol-4-ylcarbonyl) -D-alanine ester	1346
1348		1350	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-hydroxy-2- [ (methoxycarbonyl) amino]Pelargonic acid esters
1352	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (butylsulfonyl) -N- [ (6-hydroxypyridin-3-yl) carbonyl]-D-alanine esters	1350
1352		1354	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- (butylsulfonyl) -N-pyridin-3-ylcarbonyl) -D-alanine ester
1356	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N-acetyl-3- (butylsulfonyl) -D-alanine ester	1354
1356		1358	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- (cyclopropylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1360	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N-acetyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1358
1360		1362	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-isonicotinoyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1364	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-bromopyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1362
1364		1366	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-chloropyridin-3-yl) carbonyl ]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1368	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-fluorobenzoyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1366
1368		1370	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-methylpyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1372	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-phenylglycyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1370

1374	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [3- (trifluoromethyl) -1H-pyrazol-4-yl]carbonyl-D-alanine esters
1374		1376	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1378	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (1, 3-thiazol-4-ylcarbonyl) -D-alaninate	1376
1378		1380	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- [ (1-acetylpiperidin-4-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1382	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [4- (acetylamino) butanoyl group]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters	1380
1382		1384	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-acetyl-beta-alanyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1386	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (chloroacetyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1384
1386		1388	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (methoxyacetyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1390	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-methoxypropionyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1388
1390		1392	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2, 2-dimethylpropionyl) -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters
1394	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino) methyl } propyl N-isobutyryl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1392
1394		1396	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-butyryl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1398	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-acetyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1396
1398		1400	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyridin-3-ylcarbonyl) -D-alanine esters
1402	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N-isonicotinyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1400
1402		1404	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1406	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl ]-N- (pyridin-3-ylcarbonyl) -D-alanine esters	1404

1408	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1408		1410	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (cyclopropylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]-]-D-alanine esters
1412	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-propionyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1410
1412		1414	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (pyridin-3-ylcarbonyl) alanine ester
1416	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters	1414
1416		1418	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N-isonicotinyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters
1420	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- [ (6-oxo-1, 4, 5, 6-tetrahydropyridazin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1418
1420		1422	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-D-prolyl-3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride
1424	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-L-prolyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters	1422
1424		1426	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [3- (4-oxo-2-thio-1, 3-thiazolidin-3-yl) propanoyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1428	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (piperidin-4-ylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters	1426
1428		1430	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (2, 4-dimethyl-1, 3-thiazol-5-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1432	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [ 2-methyl-4- (trifluoromethyl) -1, 3-thiazol-5-yl ]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1430
1432		1434	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (3, 5-dimethylisoxazol-4-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1436	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1434
1436		1438	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (1H-pyrazol-4-ylcarbonyl) alanine ester

1440	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (1H-imidazol-5-ylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters
1440		1442	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) aminoBase of]Methyl } propyl N- (1H-imidazol-4-ylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters
1444	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyrazin-2-ylcarbonyl) alanine ester	1442
1444		1446	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- (2, 6-dihydroxyisonicotinoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters
1448	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (6-hydroxypyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters	1446
1448		1450	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (6-chloropyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1452	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-isonicotinoyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters	1450
1452		1454	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyridin-3-ylcarbonyl) alanine esters
1456	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyridin-2-ylcarbonyl) alanine esters	1454
1456		1458	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (1H-indol-6-ylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride
1460	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (3, 4, 5-trimethoxybenzoyl) alanine ester	1458
1460		1462	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2-methylbenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters
1464	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters	1462
1464		1466	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-methylbenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters
1468	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-ethylbenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters	1466
1468		1470	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-chlorobenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters
1472	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [4- (trifluoromethyl) benzoyl]Alanine esters	1470

1518	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 2- (acetoxy) -3- (butylsulfonyl) propionate
1518		1520	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl S-butyl-D-cysteine ester
1522	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfinyl) -D-alanine ester	1520
1522		1524	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- (butylsulfonic acid)Acyl) -D-alanine esters
1526	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -L-alanine ester	1524
1526		1528	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (butylsulfonyl) -D-alanine ester
1530	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1528
1530		1532	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-1-alanine esters
1534	(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- [ (1-propylbutyl) sulfonyl ]-D-alanine esters	1532
1534		1536	(1R，2S)-2-Amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters
1538	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters	1536
1538		1540	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]Alanine esters
1542	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenoxyacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters	1540
1542		1544	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [ (5-chloro-2-thienyl) thio]Peroxy } -3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1546	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters	1544
1546		1548	(1R, 2S) -3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } -2- (methylamino) propyl N- [ (benzylamino) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters
1550	4- { [ (1R, 2S) -3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } -2- (methylamino) propyl]Oxy } -4-oxo-3- { [ (1-propylbutyl) sulfonyl]Methyl butyric acid	1548

1552	4- [ ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) oxy]-3- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid
1552		1554	1- ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) 4-methyl 2- { [ (3-methylbutyl) sulfonyl]Methyl succinate
1556	(1R，2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4-amino-2- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid esters	1554
1556		1558	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- (methylamino) -2- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid esters
1560	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- (dimethylamino) -2- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid esters	1558
1560		1562	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate
1564	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate	1562
1564		1566	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-Dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate
1568	(1R, 2R) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- (ethylsulfonyl) -2- { [ (isobutylsulfonyl) amino]Methyl propionate	1566
1568		1570	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- (ethylsulfanyl) -2- { [ (isobutylsulfonyl) amino]Methyl propionate
1572	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2S) -2- { [ (3-methylbutyl) sulfonyl]Amino } -4- (methylsulfonyl) butanoic acid ester	1570
1572		1574	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (3-methylbutyl) sulfonyl group]-L-methanedisulfonic acid ester
1576	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- (acetylthio) -2- { [ (3-methylbutyl) sulfonyl]Methyl propionate	1574
1576		1578	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino ]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (1-propylbutyl) sulfonyl group]Propionic acid ester
1580	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (3-methylbutyl) sulfonyl group]Propionic acid ester	1578
1580		1582	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (3-methoxyphenyl) sulfonyl group]Propionic acid ester

1584	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4- (phenylsulfonyl) butanoate
1584		1586	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-4- [ (3-methylbutyl) sulfonyl group]Butyric ester
1588	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- [ (3-methylbutyl) sulfonyl group]-2-phenoxybutyric acid ester	1586
1588		1590	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2- (3-methoxyphenoxy) -4- [ (3-methylbutyl) sulfonyl]Butyric ester
1592	3- {1- { [ ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) oxy]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid	1590
1592		1594	3- {1- { [ ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino ]Methyl } -3-phenylpropyl) oxy]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid methyl ester
1596	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-4- (phenylsulfonyl) butanoic acid esters	1594
1596		1598	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylPropyl 2-hydroxy-4- (phenylthio) butanoic acid ester
1600	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-methoxy-4- (phenylsulfonyl) butanoic acid esters	1598
1600		1602	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-methoxy-4- (phenylthio) butanoic acid ester
1604	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- (phenylsulfonyl) -2-propoxybutyrate	1602
1604		1606	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2- (benzyloxy) -4- (phenylsulfonyl) butanoic acid esters
1608	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (benzyloxy) carbonyl]Methanedisulfonic acid ester	1606
1608		1610	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropaneThe radical (2S) -2-amino-5-oxo-5-piperidin-1-ylvalerate
1612	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino ]Methyl } -3-phenylpropyl (2S) -2- [ (2-methoxy-2-oxoethyl) amino]-5-oxo-5-piperidin-1-ylvalerate	1610
1612		1614	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2-amino-5-oxo-5-piperidin-1-ylvalerate
1616	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (2-ethoxy-2-oxoethyl) amino]-5-oxo-5-piperidin-1-ylvalerate	1614

1618	(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (4-ethoxy-4-oxobutyl) amino]-5-oxo-5-piperidin-1-ylvalerate
1618		1620	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- [ (methoxycarbonyl) amino]-4-oxooctanoate
1622	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-butyl-N- (methoxycarbonyl) -D-homoserine ester	1620
1622		1624	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxolan-2-yl) -N- (methoxycarbonyl) -D-alanine ester
1626	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (2-butyl-1, 3-dioxan-2-yl) -N- (methoxycarbonyl) -D-alanine ester	1624
1626		1628	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4, 4-difluoro-2- [ (methoxycarbonyl) amino]Octanoic acid ester
1630	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4-fluoro-2- [ (methoxycarbonyl) amino group]Octanoic acid ester	1628
1630		1632	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- [ (methoxycarbonyl) amino]-5-Oxononanoate
1634	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-hydroxy-2- [ (methoxycarbonyl) amino]Pelargonic acid esters	1632
1634		1636	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxolan-2-yl) -2- [ (methoxycarbonyl) amino]Butyric ester
1638	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxan-2-yl) -2- [ (methoxycarbonyl) amino]Butyric ester	1636
1638		1640	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl (2R) -5-fluoro-2- [ (methoxycarbonyl) amino]Pelargonic acid esters
1642	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5, 5-difluoro-2- [ (methoxycarbonyl) amino]Pelargonic acid esters	1640
1642		1644	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester
1646	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester	1644
1646		1648	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester
1650	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester	1648

1652	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({1- [3- (trifluoromethyl) phenyl)]Cyclopropyl } amino) methyl]Propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester
1652		1654	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino ]Methyl } propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters
1656	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters	1654
1656		1658	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters
1660	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters	1658
1660		1662	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({1- [3- (trifluoromethyl) phenyl)]Cyclopropyl } amino) methyl]Propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters
1664	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- { [ (methylamino) carbonyl]Amino } -4-oxooctanoic acid esters	1662
1664		1666	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-butyl-N- [ (methylamino) carbonyl ]-D-homoserine ester
1668	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxolan-2-yl) -N- [ (methylamino) carbonyl]-D-alanine esters	1666
1668		1670	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxan-2-yl) -N- [ (methylamino) carbonyl]-D-alanine esters
1672	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4, 4-difluoro-2- { [ (methylamino) carbonyl]Amino octanoate	1670
1672		1674	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4-fluoro-2- { [ (methylamino) carbonyl]Amino octanoate
1676	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- { [ (methylamino) carbonyl]Amino } -5-oxononanoic acid ester	1674
1676		1678	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-hydroxy-2- { [ (methylamino) carbonyl]Amino-nonanoic acid ester
1680	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxolan-2-yl) -2- { [ (methylamino) carbonyl ]Amino butyrate	1678
1680		1682	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl)) Amino group]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxan-2-yl) -2- { [ (methylamino) carbonyl]Amino butyrate

1537	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide
1537		1539	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide
1541	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides	1539
1541		1543	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (Phenoxyacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides
1545	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- { [ (5-chloro-2-thienyl) thio]Peroxy } -N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides	1543
1545		1547	N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides
1549	N²- [ (benzylamino) carbonyl]-N¹- [ (2R, 3S) -4- (3, 5-difluorophenyl) -2-hydroxy-3- (methylamino) butyl ]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides	1547
1549		1551	4- [ [ (2R, 3S) -4- (3, 5-difluorophenyl) -2-hydroxy-3- (methylamino) butyl](3-ethylbenzyl) amino]-4-oxo-3- { [ (1-propylbutyl) sulfonyl]Methyl butyric acid
1553	4- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl) amino]-3- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid	1551
1553		1555	4- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl) amino]-3- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid methyl ester
1557	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -2- { [ (3-methylbutyl) sulfonyl]Methyl succinamide	1555
1557		1559	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl-N¹- (3-methoxybenzyl) -N⁴-methyl-2- { [ (3-methylbutyl) sulfonyl]Methyl succinamide
1561	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -N⁴，N⁴-dimethyl-2- { [ (3-methylbutyl) sulfonyl]Methyl succinamide	1559
1561		1563	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide
1565	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide	1563
1565		1567	(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate

1569	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- (ethylsulfonyl) -2- { [ (isobutylsulfonyl) amino]Methyl } -N- (3-methoxybenzyl) propanamide
1569		1571	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- (ethylsulfanyl) -2- { [ (isobutylsulfonyl) amino]Methyl } -N- (3-methoxybenzyl) propanamide
1573	(2S) -N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -2- { [ (3-methylbutyl) sulfonyl]Amino } -4- (methylsulfonyl) butanamide	1571
1573		1575	N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -N²- [ (3-methylbutyl) sulfonyl group]-L-methanedisulfonamide
1577	S- (3- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl)](3-methoxybenzyl) amino]-2- { [ (3-methylbutyl) sulfonyl]Methyl } -3-oxopropyl) thioacetate	1575
1577		1579	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (1-propylbutyl) sulfonyl]Propionamide
1581	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (3-methylbutyl) sulfonyl group]Propionamide	1579
1581		1583	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (3-methoxyphenyl) sulfonyl]Propionamide
1585	N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4- (phenylsulfonyl) butanamide	1583
1585		1587	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -4- [ (3-methylbutyl) sulfonyl group]Butylamide
1589	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -4- [ (3-methylbutyl) sulfonyl]-2-phenoxybutanamide	1587
1589		1591	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -2- (3-methoxyphenoxy) -4- [ (3-methylbutyl) sulfonyl]Butylamide
1593	3- {1- { [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl) amino]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid	1591
1593		1595	3- {1- { [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl ](3-methoxybenzyl) amino]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid methyl ester
1597	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -4- (phenylsulfonyl) butanamide	1595
1597		1599	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -4- (phenylthio) butanamide
1601	N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N- (3-methoxybenzyl) -4- (phenylsulfonyl) butanamide	1599

Rearrangement examples

The following examples illustrate the acyl migration that occurs with the compounds of the present invention. These examples are merely illustrative and are not intended to limit the scope of the invention.

The general process comprises the following steps:

a compound of formula (I) or (X) (5mg) was dissolved in DMSO-d₆(500. mu.l) pH 4 buffer solution (500. mu.l, potassium hydrogen phthalate buffer) or pH 7 buffer solution (500. mu.l, potassium sodium phosphate buffer) was added. The sample was then heated to 40 ℃. Monitoring the migration of O-acyl or N-acyl groups to the N-terminal N-acyl group, using¹⁹F-NMR observed the chemical shift change of aromatic fluorine (the fluorine shift associated with the desired migration was confirmed by doping with authentic analogues). Used at about 0, 1.5, 3, 24, 48 and 144 hours¹⁹F-NMR analysis of the samples. The amounts of O-acyl prodrug, N-acyl prodrug and desired transfer product at each time point are obtained by integrating the corresponding NMR signals.

Example 1: specific NMR examples

N-1- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (1, 3-oxazol-2-yl) -N-3-dipropyl-N-1- [3- (trifluoromethyl) benzyl group]Isophthalamide hydrochloride (preparation 9, 5mg) was dissolved in DMSO-d₆(500. mu.l), pH was added4 buffer solution (500. mu.l, potassium hydrogen phthalate buffer). The sample was then heated to 40 ℃. Monitoring the migration of N-acyl groups to the N-terminal N-acyl group by¹⁹F-NMR observation of chemical shift changes in aromatic fluorine (by incorporation of authentic transfer product N¹- ((1S, 2R) -1- (3, 5-difluorobenzyl) -2-hydroxy-3- { [3- (trifluoromethyl) benzyl]Amino } propyl) -5- (1, 3-oxazol-2-yl) -N³，N³Dipropyl isophthalamide, confirming the fluorine shift of the desired migration product in the presence of the buffer). NMR data were collected at 0, 1, 3, 25, 48, 96 and 144 hours. The content of N-acyl prodrug and desired transfer product at each time point is determined by integrating the corresponding NMR signals. No migration to the O-acyl prodrug was observed using this method, which was confirmed by the incorporation of authentic compounds.

The following examples are set forth by way of illustration¹⁹The F NMR spectrum observed a solution acyl migration of the compounds of formula (I) and (X). Data were collected as described above in example 1.

Example 2: rearrangement of (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl ] amino } methyl) propyl 3- [ (dipropylamino) carbonyl ] -5- (1, 3-oxazol-2-yl) benzoate (22)

Prodrug HEA products

(see table)

Tables 1-2 provide the relative concentrations of prodrug 22 and its rearrangement product at different phs as a function of time.

Table 1: concentration at 40 ℃ and pH 7

pH 7，40℃
pH 7，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA¹Product of
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA¹Product of
(hr)	(% content)	(% content)	(% content)	0	100	0	0
0.5	10	0	10	0	100	0	0
0.5	10	0	10	1	0	0	100

¹HEA ═ acyl migratory hydroxyethylamine product

Table 2: concentration at 40 ℃ and pH 4

pH 4，40℃
pH 4，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	0	100	0	0
0.5	93	0	7	0	100	0	0
0.5	93	0	7	1	87	0	13
3	66	0	27	1	87	0	13
3	66	0	27	6	49	0	42
24	9	0	78	6	49	0	42
24	9	0	78	48	0	0	86

Example 3: rearrangement of (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl ] amino } methyl) propyl 3- [ (dipropylamino) carbonyl ] -5- (1, 3-oxazol-2-yl) benzoate dihydrochloride (17)

Prodrug product

Tables 3-4 provide the relative concentrations of prodrug 17 and its rearrangement product at different phs as a function of time.

Table 3: concentration at 40 ℃ and pH 7

pH 7，40℃
pH 7，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	0	100	0	0
1.5	3	0	97	0	100	0	0
1.5	3	0	97	7		0
24		0		7		0
24		0		48		0
144		0		48		0

Table 4: concentration at 40 ℃ and pH 4

pH 4，40℃
pH 4，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	0	100	0	0
1.5	53	0	47	0	100	0	0
1.5	53	0	47	3	33	0	67
6	11	0	89	3	33	0	67
6	11	0	89	24	0	0	100

Example 4: n is a radical of¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N \ 1 (u)1\ d) - (3-ethylbenzyl) -5- (1, 3-oxazol-2-yl) -N³，N³Rearrangement of dipropyl isophthalamide hydrochloride (19)

Prodrug product

Tables 5-6 provide the relative concentrations of prodrug 19 and its rearrangement product at different phs as a function of time.

Table 5: concentration at 40 ℃ and pH 7

pH 7，40℃

Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products	(hr)	(% content)	(% content)	(% content)
0	0	100	0	(hr)	(% content)	(% content)	(% content)
0	0	100	0	1	0	97	3
3	0	91	9	1	0	97	3
3	0	91	9	24	0	60	40
48	0	37	63	24	0	60	40
48	0	37	63	96	0	19	81

Table 6: concentration at 40 ℃ and pH 4

pH 4，40℃
pH 4，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	0	0	100	0
1	0	100	0	0	0	100	0
1	0	100	0	3	0	100	0
24	0	97	3	3	0	100	0
24	0	97	3	48	0	95	5
96	0	92	8	48	0	95	5

Example 5: n is a radical of¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (1, 3-oxazol-2-yl) -N³，N³-dipropyl-N¹- [3- (trifluoromethyl) benzyl group]Rearrangement of isophthalamide hydrochloride (20)

Tables 7-8 provide the relative concentrations of prodrug 20 and its rearrangement product at different phs as a function of time.

Table 7: concentration at 40 ℃ and pH 7

pH 7，40℃
pH 7，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	0	0	100	0
1	0	93	7	0	0	100	0
1	0	93	7	3	0	88	12
24	0	49	51	3	0	88	12
24	0	49	51	48	0	27	73
96	0	12	88	48	0	27	73

Table 8: concentration at 40 ℃ and pH 4

pH 4，40℃
pH 4，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs	HEA products
(hr)	(% content)	(% content)	(% content)	0	0	100	0
1	0	97	3	0	0	100	0
1	0	97	3	3	0	96	4
24	0	93	7	3	0	96	4
24	0	93	7	48	0	92	8

96

0

88

12

Example 6: rearrangement of (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ] methyl } propyl 3- [ (dipropylamino) carbonyl ] -5- (1, 3-oxazol-2-yl) benzoate dihydrochloride (16)

Product A product B

Tables 9-10 provide the relative concentrations of prodrug 16 and its rearrangement product at different phs as a function of time.

Table 9: concentration at 40 ℃ and pH 7

pH 7，40℃
pH 7，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	0	100	0	0
1.5	0	52	48	0	100	0	0

7	46	54
7	46	54	24	0	38	62
48	29	71	24	0	38	62
48	29	71	144	0	15	85

Table 10: concentration at 40 ℃ and pH 4

pH 4，40℃
pH 4，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	0	100	0	0
1.5	33	13	54	0	100	0	0
1.5	33	13	54	3	9	15	76
24	0	12	88	3	9	15	76
24	0	12	88	48	0	12	88
144	0	9	91	48	0	12	88

Example 7: rearrangement of (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl ] amino } methyl) propyl 3- [ (dipropylamino) carbonyl ] -5- (1, 3-oxazol-2-yl) benzoate dihydrochloride (18)

Product A product B

Tables 11-12 provide the relative concentrations of prodrug 18 and its rearrangement product at different phs as a function of time.

TABLE 11.40 ℃ concentration at pH 7

pH 7，40℃
pH 7，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	0	100	0	0
1.5	0	66	34	0	100	0	0
1.5	0	66	34	7	0	59	41
24	0	43	57	7	0	59	41
24	0	43	57	48	0	27	73
144	0	16	84	48	0	27	73

Table 12: concentration at 40 ℃ and pH 4

pH 4，40℃
pH 4，40℃				Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	Time of day	O-acyl prodrugs	N-acyl prodrugs (product A)	HEA product (product B)
(hr)	(% content)	(% content)	(% content)	0	100	0	0
1.5	32	14	54	0	100	0	0
1.5	32	14	54	3	8	18	74
30	0	21	79	3	8	18	74
30	0	21	79	54	0	20	80
126	0	14	86	54	0	20	80

Biological examples

Example A

Enzyme inhibition assay

The inhibitory activity of the rearranged compounds of the invention was analyzed using the MBP-C125 assay. This assay measures the relative inhibition of beta-secretase cleavage by the compound, a model APP substrate, MBP-C125SW, compared to the untreated control. Details of the measured parameters can be found, for example, in U.S. patent No.5,942,400. Briefly, the substrate is a fusion peptide consisting of Maltose Binding Protein (MBP) and APP-SW, the carboxy-terminal 125 amino acids of the Swedish mutant. Beta-secretase is derived from human brain tissue, as in Sinha et al, 1999, Nature 40: 537- & 540, or a recombinantly produced full-length enzyme (amino acids 1-501), may be prepared, for example, from 293 cells expressing recombinant cDNA, as described in WO 00/47618.

The inhibition of the enzyme is analyzed, for example, by means of an immunoassay for the enzyme cleavage products. One exemplary ELISA uses anti-MBP capture antibody deposited on a pre-coated and blocked 96-well high binding plate, followed by incubation with dilute enzyme reaction supernatant, incubation with a specific reporter antibody, e.g., biotinylated anti-SW 192 reporter antibody, and further incubation with streptavidin/alkaline phosphatase. In this assay, cleavage of the intact MBP-C125SW fusion protein resulted in the generation of a truncated amino-terminal fragment, exposing a new SW-192 antibody-positive epitope at the carboxy terminus. Detection is by means of a fluorescent substrate signal generated by phosphatase cleavage. ELISA only detected cleavage after Leu596 at the mutation site of substrate APP-SW 751.

The specific determination process comprises the following steps:

compounds were diluted 1: 1 serial dilutions to six point concentration profiles (two wells for each concentration), one for each test compound in a 96 well plate. Stock solutions of 10 millimolar of each test compound were prepared in DMSO. Stock solutions were serially diluted in DMSO, giving a final compound concentration of 200 micromolar at the high point of the 6-point dilution curve. To each of the two wells on the row C of the corresponding V-bottom plate, 10. mu.l of each dilution was added, 190. mu.l of 52 mM NaOAc, 7.9% DMSO, pH4.5 being added beforehand. The NaOAc diluted compound plate was rotated to generate a precipitate, and 20 microliters/well were transferred to the corresponding flat-bottom plate to which 30 microliters of ice-cold enzyme-substrate mixture (2.5 microliters of MBP-C125SW substrate, 0.03 microliters of enzyme, and 24.5 microliters of ice-cold 0.09% TX100 per 30 microliters) was added. The final reaction mixture of 200 micromoles of compound at the highest curve point was contained in 5% DMSO, 20 mmol NaOAc, 0.06% TX100, pH 4.5.

The plate was warmed to 37 ℃ to start the enzyme reaction. After 90 minutes at 37 ℃ the reaction was stopped by adding 200. mu.l/well of cold sample diluent and 20. mu.l/well was transferred to the corresponding anti-MBP antibody coated ELISA plate for capture, which contained 80. mu.l/well of sample diluent. This reaction was incubated overnight at 4 ℃ and the next day with anti-192 SW antibody for 2 hours, followed by treatment with streptavidin-AP conjugate and fluorescent substrate to develop the ELISA. The signal was read on a fluorescence plate reader.

The relative compound inhibitory potency was determined by calculating the concentration at which the compound showed a fifty percent reduction in the detected signal (IC) compared to the enzyme reaction signal in a control well without compound added (IC)₅₀). Preferred compounds of the invention exhibit less than 50 micromolar IC in this assay₅₀。

Example B

Cell-free inhibition assay using synthetic APP substrates

The activity of beta-secretase in the presence or absence of the inhibitory compound of the invention is measured using a synthetic APP substrate that is cleavable by beta-secretase, has an N-terminal biotin, and fluoresces at the Cys residue by covalent attachment of Oregon green. Useful substrates include the following:

biotin-sevgl-DAEFRC [ oregon green ] KK [ SEQ ID NO: 1]

biotin-SEVKM-DAEFRC [ oregon green ] KK [ SEQ ID NO: 2]

biotin-GLNIKTEEISEISY-EVEFRC [ oregon green ] KK [ SEQ ID NO: 3]

biotin-ADRGLTTRPGSGLTNIKTEEISEVNL-DAEFRC [ oregon green ] KK [ SEQ ID NO: 4]

Biotin-fvnqvqhlcoxgshlvealy-lvcoxgergftftlpkac [ oregon green ] KK [ SEQ ID NO: 5]

In pre-blocked, low affinity black plates (384 wells), the enzyme (0.1 nanomolar) and test compound (0.001-100 micromolar) were incubated at 37 ℃ for 30 minutes. The reaction was initiated by adding 150 mmol of substrate to a final volume of 30. mu.l per well. Final product of The measurement conditions were: 0.001-100 micromolar compound inhibitor; 0.1 mole sodium acetate (pH 4.5); 150 nanomolar substrate; 0.1 nanomolar soluble β -secretase; 0.001% Tween 20; and 2% DMSO. The assay mixture was incubated at 37 ℃ for 3 hours, and the reaction was stopped by adding a saturating concentration of immuno-pure streptavidin. After 15 min incubation with streptavidin at room temperature, fluorescence polarization is measured, for example, using LJL Acqurest (Ex 485nm/Em530 nm). The activity of beta-secretase is detected by means of a change in fluorescence polarization that occurs when the substrate is cleaved by the enzyme. Incubation in the presence or absence of compound inhibitors demonstrated specific inhibition of β -secretase cleavage of its synthetic APP substrate. Preferred compounds of the invention exhibit less than 50 micromolar IC in this assay₅₀。

Example C

Beta-secretase inhibition: P26-P4' SW assay

Beta-secretase activity is measured using a synthetic substrate containing the beta-secretase cleavage site of APP, using, for example, the method described in published PCT application WO 00/47618. The P26-P4' SW substrate is a peptide having the sequence:

(biotin) CGGADRGLTTRPGSGLTNIKTEEISEVNLDAEF [ SEQ ID NO: 6]

The sequences of the P26-P1 standard are:

(biotin) CGGADRGLTTRPGSGLTNIKTEEISEVNL [ SEQ ID NO: 7].

Briefly, in the present assay, a synthetic substrate coupled to biotin is incubated at a concentration of about 0 to about 200 micromolar. In testing for inhibitory compounds, a substrate concentration of about 1.0 micromolar is preferred. Test compounds diluted in DMSO were added to the reaction mixture at a final DMSO concentration of 5%. Controls also contained a final DMSO concentration of 5%. The concentration of β -secretase was varied in the reaction to obtain a product concentration in the linear range of about 125 to 2000 picomolar after dilution in an ELISA assay.

The reaction mixture also included 20 millimoles of sodium acetate, pH 4.5, 0.06% Triton X100, incubated at 37 ℃ for about 1 to 3 hours. The sample is then diluted in assay buffer (e.g., 145.4 nanomolar sodium chloride, 9.51 millimolar sodium phosphate, 7.7 millimolar sodium azide, 0.05% Triton X405, 6 g/l bovine serum albumin, pH 7.4) to stop the reaction, and then further diluted for immunoassay of the lysate.

The lysate can be assayed by ELISA. Diluted samples and standards were incubated at 4 ℃ for about 24 hours in assay plates coated with capture antibodies such as SW 192. After washing in TTBS buffer (150 mM NaCl, 25 mM Tris, 0.05% Tween 20, pH 7.5), the samples were incubated with streptavidin-AP according to the product instructions. After 1 hour incubation at room temperature, the samples were washed in TTBS and incubated with fluorogenic substrate solution A (31.2 g/l 2-amino-2-methyl-1-propanol, 30 mg/l, pH 9.5). The reaction with streptavidin-basic phosphate can be detected by fluorescence. The compounds demonstrate reduced substrate cleavage compared to controls if they are effective inhibitors of beta-secretase activity.

Example D

Assays using synthetic oligopeptide-substrates

Synthetic oligopeptides are prepared which incorporate a known beta-secretase cleavage site, and optionally a detectable label, such as a fluorescent or chromogenic moiety. Examples of such peptides and methods for their production and detection are described in U.S. Pat. No.5,942,400, which is incorporated herein by reference. The cleavage product may be detected by high performance liquid chromatography or fluorescent or chromogenic detection methods suitable for the peptide to be detected, according to methods well known in the art.

For example, one such peptide has the sequence SEVNL-DAEF [ SEQ ID NO: 8], the cleavage site is between residues 5 and 6. Another preferred substrate has the sequence ADRGLTTRPGSGLTNIKTEEISEVNL-DAEF [ SEQ ID NO: 9], the cleavage site is between residues 26 and 27.

These synthetic APP substrates are incubated in the presence of beta-secretase under conditions sufficient to result in beta-secretase-mediated cleavage of the substrates. Comparison of the cleavage results in the presence of the compound inhibitor with the control cleavage results provides a measure of the inhibitory activity of the compound.

Example E

One cell assay for inhibition of beta-secretase activity

An exemplary assay for inhibition assay of β -secretase activity employs the human embryonic kidney cell line HEKp293(ATCC accession No. CRL-1573) which is transfected with APP751 containing the naturally occurring double mutation of Lys651Met652 to Asn651Leu652 (numbering according to APP 751), commonly known as the Swedish mutation, and overproducing A β (Citron et al, 1992, Nature 360: 672-674), as described in U.S. Pat. No.5,604,102.

Cells are cultured in the presence/absence of the desired concentration, typically up to 10 micrograms/ml, of the inhibitory compound (diluted in DMSO). At the end of the treatment period, the conditioned medium is analyzed for β -secretase activity, for example by analyzing the cleaved fragments. A β can be analyzed by immunoassay using specific detection antibodies. The enzyme activity was measured in the presence and absence of compound inhibitors to demonstrate specific inhibition of β -secretase mediated cleavage of APP substrate.

Example F

Inhibition of beta-secretase in AD animal models

Various animal models can be used to screen for beta-secretase activity. Examples of animal models that can be used in the present invention include, but are not limited to, mice, guinea pigs, dogs, and the like. The animals used may be wild type, transgenic or knock out models. In addition, the mammalian model may express mutations in APP, such as APP695-SW, and the like, as described herein. Examples of transgenic non-human mammalian models are described in U.S. Pat. Nos. 5,604,102, 5,912,410 and 5,811,633.

Such as Games et al, 1995, Nature 373: 523-527 the prepared PDAPP mice can be used to analyze the in vivo inhibition of A.beta.release by putative inhibitory compounds. Compounds formulated in vehicles such as corn oil are administered to 4-month old PDAPP mice as described in us patent No.6,191,166. The compound (1-30 mg/ml; preferably 1-10mg/ml) is administered to mice. After a period of time, e.g., 3-10 hours, the animals are sacrificed and the brains removed for analysis.

Administering to the transgenic animal an amount of an inhibitor of a compound formulated in a vector appropriate for the selected mode of administration. Control animals were untreated, treated with vehicle or treated with inactive compound. Administration may be acute, i.e. a single dose or multiple doses over the course of a day, or chronic, i.e. taking up to several days per day. Starting at time 0, brain tissue or fluid is obtained from the selected animal and analyzed for the presence of APP lytic peptides, including a β, for example by immunoassay with specific a β detection antibodies. At the end of the experimental period, the animals were sacrificed and brain tissue or brain fluid was analyzed for the presence of a β and/or β -amyloid plaques. Tissue necrosis was also analyzed.

Animals receiving administration of an inhibitor of the compounds of the invention may demonstrate a reduction in a β in brain tissue or brain fluid and a reduction in β -amyloid plaques in brain tissue as compared to untreated controls.

Example G

Inhibition of A beta production in human patients

Patients with Alzheimer's Disease (AD) demonstrate increased amounts of a β in the brain. Administering to an AD patient an amount of an inhibitor of a compound formulated in a carrier suitable for the selected mode of administration. Daily dosing was used during the test period. From day 0, cognitive and memory tests are performed, for example once a month.

Patients receiving administration of the compound inhibitor may demonstrate a delay or stabilization of disease progression as compared to controls, i.e., untreated patients, as analyzed by changes in one or more of the following disease parameters: a β present in CSF or plasma; brain or hippocampal volume; a β deposits in the brain; amyloid plaques in the brain; and cognitive and memory function scores.

Example H

Inhibition of A beta production in patients at risk for AD

Patients susceptible to or at risk of developing AD are identified by identification of familial genetic patterns, such as the presence of swedish mutations, and/or by monitoring diagnostic parameters. Administering to a patient determined to be susceptible to or at risk of developing AD an amount of an inhibitor of a compound formulated in a carrier appropriate to the mode of administration selected. Daily dosing was used during the test period. From day 0, cognitive and memory tests are performed, for example once a month.

Patients receiving administration of the compound inhibitor may demonstrate a delay or stabilization of disease progression as compared to controls, i.e., untreated patients, as analyzed by changes in one or more of the following disease parameters: a β present in CSF or plasma; brain or hippocampal volume; amyloid plaques in the brain; and cognitive and memory function scores.

The invention has now been described with reference to various specific and preferred embodiments and techniques. It should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention.

Reaction scheme A

Reaction scheme B

Reaction scheme C

Reaction scheme D

Reaction scheme E

(XX1)＝(X₃-O-)₂PO-CH (NH-protecting group) -CO-R₁

Claims

1. A compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein

R_NAnd R_NOne of them is hydrogen, and the other is hydrogen,

Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, arylalkyl, alkanoyl or arylalkanoyl;

R_4-6is-H or C₁-C₆An alkyl group;

R₅selected from: c₃-C₇A cycloalkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl group, C₆-C₁₀Aryl radical, C₃-C₇Cycloalkyl radical C₁-C₄Alkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl radical, C₆-C₁₀An aryloxy group; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; aryl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₆And R₇Independently selected from H, C₁-C₆Alkyl radical, C₂-C₆Alkanoyl and phenyl、-SO₂-C₁-C₄Alkyl, phenyl C₁-C₄An alkyl group;

R₉Is aryl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: aryl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently selected from halogen, cyano, heteroaryl, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇Cycloalkyl or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, aryl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); an aryl group; a heterocycloalkyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the aryl, heterocycloalkyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group;

R₅₂is heterocycloalkyl, heteroaryl, aryl, cycloalkyl, -S (O)_0-2-C₁-C₆Alkyl, CO₂H、-C(O)NH₂-C (O) NH (alkyl), -C (O) N (alkyl), -CO₂-alkyl, -NHS (O)_0-2-C₁-C₆Alkyl, -N (alkyl) S (O)_0-2-C₁-C₆Alkyl, -S (O)_0-2-heteroaryl, -S (O)_0-2-aryl, -NH (arylalkyl), -N (alkyl) (arylalkyl), thioalkoxy or alkoxy, each of which is optionally substituted with 1, 2, 3, 4 or 5 groups, which are independently alkyl, alkoxy, thioalkoxy, halogen, haloalkyl, haloalkoxy, alkanoyl, NO₂CN, alkoxycarbonyl or aminocarbonyl;

R₅₃is a bond, -O-, -C (O) -, -NH-, -N (alkyl) -, -NH-S (O) _0-2-, -N (alkyl) -S (O)_0-2-、-S(O)_0-2-NH-、-S(O)_0-2-N (alkyl) -, -NH-c(s) -or-N (alkyl) -c(s) -;

R₄And R_4-6Combined to form- (CH)₂)_n10-, wherein

n₁₀Is 1, 2, 3 or 4;

z is selected from the group consisting of a bond, SO₂SO, S and C (O);

y is selected from: h; c₁-C₄A haloalkyl group; c₅-C₆A heterocycloalkyl group; c₆-C₁₀An aryl group; OH; -N (Y)₁)(Y₂)；C₁-C₁₀Alkyl, optionally substituted with 1 to 3 substituents, which may be the same or different, selected from halogen, hydroxy, alkoxy, thioalkoxy and haloalkoxy; c₃-C₈Cycloalkyl optionally substituted with 1, 2 or 3 groups independently selected from C ₁-C₃Alkyl and halogen; an alkoxy group; aryl, optionally substituted by halogen, alkyl, alkoxy, CN or NO₂Substitution; arylalkyl, optionally substituted by halogen, alkyl, alkoxy, CN or NO₂Substitution; wherein

Y₁And Y₂Are identical or different and are H; c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 substituents selected from halogen, C₁-C₄Alkoxy radical, C₃-C₈Cycloalkyl and OH; c₂-C₆An alkenyl group; c₂-C₆An alkanoyl group; a phenyl group; -SO₂-C₁-C₄An alkyl group; phenyl radical C₁-C₄An alkyl group; or C₃-C₈Cycloalkyl radical C₁-C₄Alkyl radicalOr is or

Y₁、Y₂And the nitrogen to which they are attached form a ring selected from piperazinyl, piperidinyl, morpholinyl and pyrrolidinyl, wherein each ring is optionally substituted with 1, 2, 3 or 4 groups, which are independently C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl or halogen; r₁Is- (CH)₂)_1-2-S(O)_0-2-(C₁-C₆Alkyl) or

C₂-C₆Alkenyl or C₂-C₆Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF ₃、C₁-C₃Alkoxy, amino and mono-or dialkylamino, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl, each of which is optionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF ₃、C₁-C₃Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and is

Heterocyclyl is optionally further substituted by oxo;

r and R' are independently hydrogen or C₁-C₁₀An alkyl group;

R₂selected from: h; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents independently selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy and-NR_1-aR_1-bWherein R is_1-aAnd R_1-bis-H or C₁-C₆An alkyl group; - (CH)₂)_0-4-an aryl group; - (CH)₂)_0-4-a heteroaryl group; c₂-C₆An alkenyl group; c₂-C₆An alkynyl group; -CONR_N-2R_N-3；-SO₂NR_N-2R_N-3；-CO₂H; and-CO²-(C₁-C₄Alkyl groups);

R₃selected from: h; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents independently selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF₃、C₁-C₃Alkoxy and-NR_1-aR_1-b；-(CH₂)_0-4-an aryl group; - (CH)₂)_0-4-a heteroaryl group; c₂-C₆An alkenyl group; c₂-C₆An alkynyl group; -CO-NR_N-2R_N-3；-SO₂-NR_N-2R_N-3；-CO₂H; and-CO-O- (C)₁-C₄Alkyl) or

R_Cselected from: c₁-C₁₀Alkyl optionally substituted with 1, 2 or 3 groups independently selected from R₂₀₅、-OC＝ONR₂₃₅R₂₄₀、-S(＝O)_0-2(C₁-C₆Alkyl), -SH, -NR₂₃₅C＝ONR₂₃₅R₂₄₀、-C＝ONR₂₃₅R₂₄₀and-S (═ O)₂NR₂₃₅R₂₄₀；-(CH₂)_0-3-(C₃-C₈) Cycloalkyl, wherein the cycloalkyl is optionally substituted with 1, 2 or 3 groups independently selected from R ₂₀₅、-CO₂H and-CO₂-(C₁-C₄Alkyl groups); - (CR)₂₄₅R₂₅₀)_0-4-an aryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heteroaryl group; - (CR)₂₄₅R₂₅₀)_0-4-a heterocycloalkyl group; - (CR)₂₄₅R₂₅₀)_0-4-aryl-heteroaryl; - (CR)₂₄₅R₂₅₀)_0-4-aryl-heterocycloalkyl; - (CR)₂₄₅R₂₅₀)_0-4-aryl; - (CR)₂₄₅R₂₅₀)_0-4-heteroaryl-aryl; - (CR)₂₄₅R₂₅₀)_0-4-heteroaryl-heterocycloalkyl; - (CR)₂₄₅R₂₅₀)_0-4-heteroaryl; - (CR)₂₄₅R₂₅₀)_0-4-heterocycloalkyl-heteroaryl; - (CR)₂₄₅R₂₅₀)_0-4-heterocycloalkyl; - (CR)₂₄₅R₂₅₀)_0-4-heterocycloalkyl-aryl; - [ C (R)₂₅₅)(R₂₆₀)]_1-3-CO-N-(R₂₅₅)₂(ii) a -CH (aryl)₂(ii) a -CH (heteroaryl)₂(ii) a -CH (heterocycloalkyl)₂(ii) a -CH (aryl) (heteroaryl); a cyclopentyl, cyclohexyl or cycloheptyl ring fused to an aryl, heteroaryl or heterocycloalkyl group, wherein one carbon of the cyclopentyl, cyclohexyl or cycloheptyl group is optionally replaced by NH, NR₂₁₅O or S (═ O)_0-2And wherein the cyclopentyl, cyclohexyl, or cycloheptyl groups can optionally be substituted with 1 or 2 groups which are independently R₂₀₅Or ═ O; -CO-NR₂₃₅R₂₄₀；-SO₂-(C₁-C₄Alkyl groups); c₂-C₁₀Alkenyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₁₀Alkynyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (CH)₂)_0-1-CH((CH₂)_0-6-OH)-(CH₂)_0-1-an aryl group; - (CH)₂)_0-1-CHR_C-6-(CH₂)_0-1-a heteroaryl group; -CH (-aryl or-heteroaryl) -CO-O (C)₁-C₄Alkyl groups); -CH (-CH)₂-OH) -CH (OH) -phenyl-NO₂；(C₁-C₆Alkyl) -O- (C₁-C₆Alkyl) -OH; -CH₂-NH-CH₂-CH(-O-CH₂-CH₃)₂(ii) a -H; and- (CH)₂)_0-6-C(＝NR₂₃₅)(NR₂₃₅R₂₄₀) Wherein

Each aryl group is optionally substituted by 1, 2 or 3R ₂₀₀Substitution;

Wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R ₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group;

R₂₁₅Independently at each occurrence is selected from C₁-C₆Alkyl, - (CH)₂)_0-2- (aryl), C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₃-C₇Cycloalkyl, - (CH)₂)_0-2- (heteroaryl), - (CH)₂)_0-2- (heterocycloalkyl) in which aryl is optionally substituted at each occurrence with 1, 2 or 3 groups which are independently R₂₀₅Or R₂₁₀(ii) a Wherein heterocycloalkyl is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution; wherein each heteroaryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₁₀Substitution;

R₂₂₀and R₂₂₅Independently at each occurrence is selected from-H, -C₁-C₆Alkyl, hydroxy C₁-C₆Alkyl, amino C ₁-C₆Alkyl, halo C₁-C₆Alkyl, -C₃-C₇Cycloalkyl, - (C)₁-C₂Alkyl group) - (C₃-C₇Cycloalkyl), - (C)₁-C₆Alkyl) -O- (C₁-C₃Alkyl), -C₂-C₆Alkenyl, -C₂-C₆Alkynyl, -C having a double bond and a triple bond₁-C₆Alkyl chains, -aryl, -heteroaryl and-heterocycloalkyl, wherein the aryl group is optionally substituted at each occurrence with 1, 2 or 3R₂₇₀Substituted by groups; wherein

R₂₅₅And R₂₆₀Independently at each occurrence is selected from: h; c₁-C₆Alkyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkenyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; c₂-C₆Alkynyl, optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (CH)₂)_1-2-S(O)_0-2-(C₁-C₆Alkyl groups); - (CH)₂)_0-4-C₃-C₇Cycloalkyl optionally substituted by 1, 2 or 3R₂₀₅Substituted by groups; - (C)₁-C₄Alkyl) -aryl; - (C)₁-C₄Alkyl radical) -a heteroaryl group; - (C)₁-C₄Alkyl) -heterocycloalkyl; -an aryl group; -a heteroaryl group; -a heterocycloalkyl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-an aryl group; - (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-a heteroaryl group; and- (CH)₂)_1-4-R₂₆₅-(CH₂)_0-4-a heterocycloalkyl group,

wherein

R₂₆₅Independently at each occurrence is-O-, -S-or-N (C)₁-C₆Alkyl) -;

each aryl or phenyl group is optionally substituted with 1, 2 or 3 groups which are independently R₂₀₅、R₂₁₀Or by 1, 2 or 3 independently R₂₀₅Or R₂₁₀C substituted by a group of₁-C₆An alkyl group;

R₁₀₀and R'₁₀₀Independently represents aryl, heteroaryl, heterocyclyl, -aryl-W-aryl, -aryl-W-heteroaryl, -aryl-W-heterocyclyl, -heteroaryl-W-aryl, heteroaryl-W-heteroaryl, -heteroaryl-W-heterocyclyl, -heterocyclyl-W-aryl, -heterocyclyl-W-heteroaryl, -heterocyclyl-W-heterocyclyl, -CH [ (CH) ₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-aryl, -CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-heterocyclyl or-CH [ (CH)₂)_0-2-O-R₁₅₀]-(CH₂)_0-2-heteroaryl, wherein the cyclic moiety of each group is optionally substituted with 1, 2 OR 3 groups independently selected from-OR, -NO₂、C₁-C₆Alkyl, halogen, -C.ident.N, -OCF₃、-CF₃、-(CH₂)_0-4-O-P(＝O)(OR)(OR′)、-(CH₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-(CH₂)_0-4-CONR₁₀₂R₁₀₂′、-(CH₂)_0-4-CO-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkenyl), - (CH)₂)_0-4-CO-(C₂-C₁₂Alkynyl), - (CH)₂)_0-4-CO-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀、-(CH₂)_0-4-CO-R₁₁₀、-(CH₂)_0-4-CO-R₁₂₀、-(CH₂)_0-4-CO-R₁₃₀、-(CH₂)_0-4-CO-R₁₄₀、-(CH₂)_0-4-CO-O-R₁₅₀、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-SO-(C₁-C₈Alkyl), - (CH)₂)_0-4-SO₂-(C₁-C₁₂Alkyl), - (CH)₂)_0-4-SO₂-(CH₂)_0-4-(C₃-C₇Cycloalkyl), - (CH)₂)_0-4-N(R₁₅₀)-CO-O-R₁₅₀、-(CH₂)_0-4-N(R₁₅₀)-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CS-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-CO-R₁₀₅、-(CH₂)_0-4-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-R₁₄₀、-(CH₂)_0-4-O-CO-(C₁-C⁶Alkyl), - (CH)₂)_0-4-O-P(O)-(O-R₁₁₀)₂、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-O-CS-N(R₁₅₀)₂、-(CH₂)_0-4-O-(R₁₅₀)、-(CH₂)_0-4-O-R₁₅₀′-COOH、-(CH₂)_0-4-S-(R₁₅₀)、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl and (C)₂-C₁₀) Alkynyl, or

C₁-C₆Alkyl, optionally substituted by-OH or-NH₂Is substituted, or

R₁₀₅And R'₁₀₅Together with the atom to which they are attached form 3 toA 7 membered carbocyclic ring, wherein one atom is optionally selected from-O-, -S (O)_0-2-、-N(R₁₃₅) -said ring being optionally substituted with 1, 2 or 3 groups independently selected from R₁₄₀A group;

R₁₄₅is C₁-C₆Alkyl or CF ₃；

R₁₈₀selected from morpholinyl, thiomorpholinyl, piperazinyl, piperidinyl, homomorpholinylThiomorpholinyl, thiomorpholinyl S-oxide, thiomorpholinyl S, S-dioxide, pyrrolinyl and pyrrolidinyl, each of which is optionally substituted by 1, 2, 3 or 4 groups selected from C₁-C₆Alkyl radical, C₁-C₆Alkoxy, halogen, hydroxy, cyano, nitro, amino, mono (C) ₁-C₆) Alkylamino radical, di (C)₁-C₆) Alkylamino radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Haloalkyl, C₁-C₆Halogenoalkoxy, amino (C)₁-C₆) Alkyl, mono (C)₁-C₆) Alkylamino radical (C)₁-C₆) Alkyl, di (C)₁-C₆Alkyl) amino (C)₁-C₆) Alkyl and ═ O;

C₁-C₆Alkoxy optionally substituted with 1, 2 or 3 halo;

R₁₃₀is a heterocyclic radical, optionallyBy 1 or 2R₁₂₅And (4) substituting the group.

2. A compound according to claim 1, wherein R_NIs hydrogen.

3. A compound according to claim 1, wherein R_N' is hydrogen.

4. A compound according to claim 1, wherein

R₁is-C₁-C₆Alkyl-aryl, -C₁-C₆Alkyl-heteroaryl or-C₁-C₆Alkyl-heterocyclyl, wherein the ring portion of each group is optionally substituted with 1, 2, 3 or 4 groups independently selected from halogen, -OH, -SH, -C ≡ N, -NO ₂、-NR₁₀₅R′₁₀₅、-CO₂R, -N (R) COR' or-N (R) SO₂R′，-C(＝O)-(C₁-C₄) Alkyl, -SO₂-amino, -SO₂-mono-or dialkylamino, -C (═ O) -amino, -C (═ O) -mono-or dialkylamino, -SO₂-(C₁-C₄) Alkyl, or

C₂-C₁₀Alkenyl or C₂-C₁₀Alkynyl radicals, each of themOptionally substituted with 1, 2 or 3 groups independently selected from halogen, -OH, -SH, -C ≡ N, -CF₃、C₁-C₃Alkoxy, amino, C₁-C₆Alkyl and mono-or dialkylamino; and the heterocyclyl is optionally further substituted by oxo.

5. A compound according to claim 1, wherein

R₂And R₃Independently selected from H or C₁-C₆Alkyl optionally substituted with 1, 2 or 3 substituents selected from C₁-C₃Alkyl, halogen, -OH, -SH, -C.ident.N, -CF ₃、C₁-C₃Alkoxy and-NR_1-aR_1-b。

6. A compound according to claim 1, wherein

7. A compound according to claim 2, wherein

R_N' is

Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO ₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl, or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group.

8. A compound according to claim 3, wherein

R_NIs that

Wherein

n₆Is 0, 1, 2 or 3;

n₇is 0, 1, 2 or 3;

R_4-4is alkyl, phenylalkyl, C₂-C₄Alkanoyl or phenylalkanoyl;

R₅is cyclopropyl; a cyclobutyl group; a cyclopentyl group; or cyclohexyl; wherein each cycloalkyl group is optionally substituted with 1 or 2 groups, the substituent group being C₁-C₆Alkyl, more preferably C₁-C₂Alkyl radical, C₁-C₆Alkoxy, more preferably C₁-C₂Alkoxy radical, CF₃，OH，NH₂，NH(C₁-C₆Alkyl radical, N (C)₁-C₆Alkyl) (C₁-C₆Alkyl), halogen, CN or NO₂(ii) a Or the cycloalkyl is substituted with 1 or 2 groups which are independently CF₃Cl, F, methyl, ethyl or cyano; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, -NR₆R₇、C₁-C₄Alkoxy radical, C₅-C₆Heterocycloalkyl radical, C₅-C₆Heteroaryl, phenyl, C₃-C₇Cycloalkyl, -S-C₁-C₄Alkyl, -SO₂-C₁-C₄Alkyl, -CO₂H、-CONR₆R₇、-CO₂-C₁-C₄Alkyl, or phenoxy; heteroaryl optionally substituted with 1, 2 or 3 groups independentlyIs C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₁-C₄Haloalkyl or OH; heterocycloalkyl, optionally substituted with 1, 2 or 3 groups which are independently C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen or C₂-C₄An alkanoyl group; phenyl optionally substituted with 1, 2, 3 or 4 groups independently being halogen, OH, C₁-C₄Alkyl radical, C₁-C₄Alkoxy or C₁-C₄A haloalkyl group; and-NR₆R₇Wherein

R₉Is phenyl C₁-C₄Alkyl radical, C₁-C₆Alkyl or H;

R₅₀is H or C₁-C₆An alkyl group;

R₅₁selected from: phenyl radical C₁-C₄An alkyl group; c₁-C₆Alkyl optionally substituted with 1, 2 or 3 groups independently being halogen, cyano, -NR₆R₇、-C(O)NR₆R₇、C₃-C₇or-C₁-C₄An alkoxy group; heterocycloalkyl, optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; heterocycloalkylalkyl optionally substituted with 1 or 2 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, C₂-C₄Alkanoyl, phenyl C₁-C₄Alkyl and-SO₂-C₁-C₄An alkyl group; an alkenyl group; an alkynyl group; heteroaryl, optionally substituted with 1, 2 or 3 groups which are independently OH, C ₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); heteroarylalkyl optionally substituted with 1, 2 or 3 groups which are independently C₁-C₄Alkyl radical, C₁-C₄Alkoxy, halogen, NH₂、NH(C₁-C₆Alkyl) or N (C)₁-C₆Alkyl) (C₁-C₆Alkyl groups); a phenyl group; c₃-C₈A cycloalkyl group; and cycloalkylalkyl, wherein the phenyl, C₃-C₈Cycloalkyl and cycloalkylalkyl are optionally substituted with 1, 2, 3, 4 or 5 groups which are independently halogen, CN, NO₂、C₁-C₆Alkyl radical, C₁-C₆Alkoxy radical, C₂-C₆Alkanoyl radical, C₁-C₆Haloalkyl, C₁-C₆Haloalkoxy, hydroxy, C₁-C₆Hydroxyalkyl radical, C₁-C₆Alkoxy radical C₁-C₆Alkyl radical, C₁-C₆Thioalkoxy radical, C₁-C₆Thioalkoxy radical C₁-C₆Alkyl or C₁-C₆Alkoxy radical C₁-C₆An alkoxy group.

9. A compound according to claim 2, wherein

R_N' is-C (═ O) -phenyl, wherein the phenyl ring is optionally substituted with 1 or 2 groups independently selected from C₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl, - (CH)₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₀) Alkynyl.

10. A compound according to claim 3, wherein

R_Nis-C (═ O) -phenyl, wherein the phenyl ring is optionally substituted with 1 or 2 groups independently selected from C₁-C₆Alkyl, halogen, - (CH)₂)_0-4-CO-NR₁₀₅R′₁₀₅、-(CH₂)_0-4-O-CO-N(R₁₅₀)₂、-(CH₂)_0-4-N(R₁₅₀)-SO₂-R₁₀₅、-(CH₂)_0-4-SO₂-NR₁₀₅R′₁₀₅、C₃-C₇Cycloalkyl group, (C)₂-C₁₀) Alkenyl, - (CH) ₂)_0-4-R₁₁₀、-(CH₂)_0-4-R₁₂₀、-(CH₂)_0-4-R₁₃₀Or (C)₂-C₁₀) Alkynyl.

11. A compound according to claim 1, selected from the following: N¹- [ (2R, S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -D-alaninamide dihydrochloride N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine amide trifluoroacetate salt N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (methylsulfonyl) amino]-1, 3-thiazole-5-carboxamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-L-alaninamide bis (trifluoroacetate) N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N- (3-ethylbenzyl) propionamide hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) propionate dihydrochloride

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoate dihydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylbenzyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoate dihydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoate dihydrochloride N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N (u)1(d) - (3-ethylbenzyl) -5- (1, 3-oxazol-2-yl) -N³，N³Salts of (E) -dipropyl-isophthalamide with hydrochloric acid N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (1, 3-oxazol-2-yl) -N³，N³-dipropyl-N¹- [3- (trifluoromethyl) benzyl group]Isophthalamide hydrochloride N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (1, 3-oxazol-2-yl) -N³，N³-dipropyl-N¹- [3- (trifluoromethyl) benzyl group]M-phenylene diamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -N²- [ (methoxy) carbonyl]-D-alaninamide dihydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- { [ (2-hydroxyethyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (2-isobutyl-1, 3-thiazol-5-yl) methyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-isopropylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-isopropylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- { [ (2-hydroxy-1, 1-dimethylethyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl ]-5- (4-methyl-1, 3-oxazol-2-yl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (2-isobutyl-1, 3-thiazol-5-yl) methyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- { [ (3-hydroxypropyl) amino]Sulfonyl benzoate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-propylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ butyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (3-isobutylisoxazol-5-yl) methyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (dimethylamino) sulfonyl group]-5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (5-formyl-2-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 3-bromo-5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- ({ [ (1R) -2-hydroxy-1-methylethyl)]Amino } sulfonyl) benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-isobutylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- { [ (2R) -2- (methoxymethyl) pyrrolidin-1-yl]Carbonyl } -5-methylbenzoate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- ({ [ (1S) -2-hydroxy-1-methylethyl)]Amino } sulfonyl) benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ butyl (propyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dibutylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3-hydroxypropan-1-yn-1-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- { [ (2S) -2- (hydroxymethyl) pyrrolidin-1-yl]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ butyl (ethyl) amino]Carbonyl } -5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ cyclohexyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-1- ({ [3- (cyclopropylamino) benzyl]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (piperazin-1-ylsulfonyl) benzoate dihydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-iodophenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-sec-butylbenzyl) amino ]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (3-methylisoxazol-4-yl) benzoic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-isobutylisoxazol-5-yl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- [ (dipropylamino) carbonyl]-6-methylisonicotinic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (cyclopropylmethyl) (propyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl ]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (aminosulfonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (1Z) -prop-1-en-1-yl)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1H-pyrazol-4-yl) benzoic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) -1-methylethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -1- { [ (3-allylbenzyl) amino]Methyl } -2-amino-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl ]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) -1-methylethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ ethyl (propyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-1- ({ [3- (cyclopropylamino) benzyl]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-isobutylisoxazol-5-yl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (5-formyl-4-methyl-2-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-isopropylbenzyl) amino ]Methyl } propyl 5- [ (dipropylamino) carbonyl]Nicotinic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (methylsulfonyl) amino group)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (butylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3-methylbutyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (biphenyl-3-ylmethyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- ({ [2- (methylamino) ethyl]Amino } sulfonyl) benzoate hydrochloride (1R, 2S) -2-Ammonia3- (3, 5-difluorophenyl) -1- ({ [1- (3-isobutylisoxazol-5-yl) cyclopropyl-amino ]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-ethynylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (diallylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2R) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (2-isobutyl-1, 3-thiazol-5-yl) cyclopropyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) -1-methylethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (2-hydroxyethyl) amino]Sulfonyl } -5- [ (propylamino) carbonyl group]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (propyl) amino]Carbonyl benzoate ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (diethylamino) carbonyl group]-5- (1, 3-oxazol-2-yl) benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzylamino) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine ester trifluoroacetate salt (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-pyridin-3-ylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- [ (dipropylamino) carbonyl]Nicotinate 1-oxides (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3-formyl-2-furyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5- (1-methyl-1H-imidazol-2-yl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (diethylamino) carbonyl group]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (ethylsulfinyl) benzyl ]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ butyl (ethyl) amino]Sulfonyl } propanoate

(1R, 2S) -2-amino-1- { [ (3-cyanobenzyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propane3- [ (1-propylbutyl) sulfonyl ] group]Propionic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ isobutyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-pyridin-2-ylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 2- [ (methylsulfonyl) amino group]-1, 3-oxazole-4-carboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ methyl (methylsulfonyl) amino)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-phenylpropionyl) -3- [ (1-propylbutyl) sulfonyl]Alanine ester trifluoroacetate salt (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (ethylsulfonyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-chloro-2-thienyl) sulfonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine ester hydrochloride (1R, 2S) -1- ({ [3- (5-acetyl-2-thienyl) benzyl]Amino } methyl) -2-amino-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (sec-butylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1, 3-oxazol-2-yl) benzoate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (2-phenylethyl) amino ]Carbonyl benzoate ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (3, 5-dimethylisoxazol-4-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (prop-2-yn-1-yl) amino]Carbonyl benzoate ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ ethyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3- { [ (dimethylamino) carbonyl]Oxy } benzyl) amino]Methyl } propyl 3- (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl radical]Propyl 3- { [ benzyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ sec-butyl (propyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (4-methyl-2-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (methoxycarbonyl) (methyl) amino group]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) -3- (2, 3, 5-trifluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (diisobutylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-5- { [ methyl (2-pyridin-2-ylethyl) amino]Carbonyl benzoate ester (1R, 2S) -2-amino-3- (3-fluoro-5-hydroxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-Methylbenzoic acid ester hydrochloride (1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 4-hydroxy-3- (pyrrolidin-1-ylcarbonyl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-D-prolyl-3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-pyridin-4-ylbenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (dimethylamino) sulfonyl)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (6-methoxy-1, 2, 3, 4-tetrahydronaphthalen-1-yl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (azepan-1-ylcarbonyl) -5-methylbenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (methoxycarbonyl) amino group]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-L-prolyl-3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (isobutylamino) carbonyl]-5-methylbenzoic acid ester 4- [ ((1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl) oxy]-4-oxo-3- { [ (1-propylbutyl) sulfonyl]Trifluoroacetic acid methyl ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ methyl (methylsulfonyl) amino]Benzoic acid esters N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2-hydroxyethyl) amino]Sulfonyl } -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- [ (2-isobutyl-1, 3-thiazol-5-yl) methyl]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- (3-isopropylbenzyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-isopropylbenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2-hydroxy-1, 1-dimethylethyl) amino]Sulfonyl } -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (4-methyl-1, 3-oxazol-2-yl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (2-isobutyl-1, 3-thiazol-5-yl) methyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (3-hydroxypropyl) amino]Sulfonyl } -N ', N' -dipropyl-isophthalamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- (3-propylbenzyl) isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-butyl-N- (3-ethylbenzyl) -N', 5-dimethyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- (3-ethynylbenzyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- [ (3-isobutylisoxazol-5-yl) methyl]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- [ (dimethylamino) sulfonyl group]-N- (3-ethylbenzyl) -N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (5-formyl-2-thienyl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino group-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-bromo-N- (3-iodobenzyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- ({ [ (1R) -2-hydroxy-1-methylethyl]Amino } sulfonyl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-isobutylbenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2R) -2- (methoxymethyl) pyrrolidin-1-yl]Carbonyl } -5-methylbenzamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- ({ [ (1S) -2-hydroxy-1-methylethyl)]Amino } sulfonyl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-butyl-N- (3-ethylbenzyl) -5-methyl-N' -propyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N ', N' -dibutyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (3-hydroxyprop-1-yn-1-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluoro) Phenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2S) -2- (hydroxymethyl) pyrrolidin-1-yl]Sulfonyl } -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-butyl-N' -ethyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethynylbenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-cyclohexyl-N- (3-ethylbenzyl) -N', 5-dimethyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (cyclopropylamino) benzyl]-5-ethynyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- [3- (3-thienyl) benzyl]M-phenylene diamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -5- (piperazin-1-ylsulfonyl) -N ', N' -dipropyl-isophthalamide dihydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-iodophenyl) cyclopropyl]-5-methyl-N ', N' -dipropylMetaphenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-sec-butylbenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (3-methylisoxazol-4-yl) -N ', N' -dipropyl isophthalamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-isobutylisoxazol-5-yl) cyclopropyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethylphenyl) cyclopropyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide N⁴- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N⁴- (3-ethylbenzyl) -6-methyl-N²，N²-dipropylpyridine-2, 4-dicarboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N '- (cyclopropylmethyl) -N- (3-ethylbenzyl) -5-methyl-N' -propyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethynylphenyl) cyclopropyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (Ammonia)Methylsulfonyl) -N- (3-ethylbenzyl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- {3- [ (1Z) -prop-1-en-1-yl]Benzyl } -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', N' -dipropyl-5- (1H-pyrazol-4-yl) isophthalamide dihydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethylphenyl) -1-methylethyl]-5-ethynyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-5-methyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide N- (3-allylbenzyl) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethylphenyl) cyclopropyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethylphenyl) -1-methylethyl]-5- (1, 3-oxazol-2-yl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-Ethyl-N- (3-ethylbenzyl) -5-methyl-N' -propylisophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (cyclopropylamino) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- [1- (3-ethynylphenyl) cyclopropyl]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-isobutylisoxazol-5-yl) cyclopropyl ]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (5-formyl-4-methyl-2-thienyl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-isopropylbenzyl) -N ', N' -dipropylpyridine-3, 5-dicarboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- {3- [ (methylsulfonyl) amino group]Benzyl } -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' -butyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [3- (3-methylbutyl) benzyl]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (biphenyl-3-ylmethyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethynylphenyl) cyclopropyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- ({ [2- (methylamino) ethyl)]Amino } sulfonyl) -N ', N' -dipropyl isophthalamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-ethynyl-N- [1- (3-isobutylisoxazol-5-yl) cyclopropyl]-N ', N' -dipropyl-isophthalamide N, N-diallyl-N' - [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (3-ethylbenzyl) -5-methyl-m-phenylenediamine N- [ (2R, 3R) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (2-isobutyl-1, 3-thiazol-5-yl) cyclopropyl ] amine]-5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (3-ethylphenyl) -1-methylethyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- { [ (2-hydroxyethyl) amino]Sulfonyl } -N' -propyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' -propylisophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluoro)Phenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N ', N' -diethyl-N- (3-ethylbenzyl) -5- (1, 3-oxazol-2-yl) isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- [ (benzylamino) carbonyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide trifluoroacetate salt N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- (3-pyridin-3-ylbenzyl) isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', N' -dipropylpyridine-3, 5-dicarboxamide 1-oxide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' -Ethyl-N- [3- (3-formyl-2-furyl) benzyl]-5-methyl-N' -propyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (1-methyl-1H-imidazol-2-yl) -N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N ', N' -diethyl-N- (3-ethylbenzyl) -5-methylisophthalimide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (ethylsulfinyl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- { [ butyl (ethyl) amino]Sulfonyl } -N- (3-ethylbenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-cyanobenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Propionamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N '-isobutyl-N', 5-dimethyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- (3-pyridin-2-ylbenzyl) isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-iodobenzyl) -2- [ (methylsulfonyl) amino ]-1, 3-oxazole-4-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- {3- [ methyl (methylsulfonyl) amino]Benzyl } -N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (3-phenylpropionyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide trifluoroacetate salt N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (ethylsulfonyl) benzyl]-5-methyl-N'N' -Dipropylisophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- [ (5-chloro-2-thienyl) sulfonyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride N- [3- (5-acetyl-2-thienyl) benzyl]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (sec-butyl) -N- (3-ethylbenzyl) -5-methyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (1, 3-oxazol-2-yl) benzamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' - (2-phenylethyl) isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (3, 5-dimethylisoxazol-4-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' -prop-2-yn-1-yl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-Ethyl-N- (3-ethylbenzyl) -N', 5-dimethyl isophthalamide 3- [ ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) methyl]Phenyl dimethyl carbamate N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-benzyl-N- (3-ethylbenzyl) -N', 5-dimethyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '- (sec-butyl) -N- (3-ethylbenzyl) -5-methyl-N' -propyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-5-methyl-N- [3- (4-methyl-2-thienyl) benzyl]-N ', N' -dipropyl-isophthalamide {3- [ ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) methyl]Phenyl } methyl carbamate

N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2, 3, 5-trifluorophenyl) butyl]-5-methyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', N' -diisobutyl-5-methylisophthalimide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', 5-dimethyl-N' - (2-pyridin-2-ylethyl) isophthalamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-5-hydroxyphenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide hydrochloride N¹- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4-hydroxy-N- (3-iodobenzyl) -3- (pyrrolidin-1-ylcarbonyl) benzamide 5-oxo-D-prolyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-N- (3-pyridin-4-ylbenzyl) isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- {3- [ (dimethylamino) sulfonyl group]Benzyl } -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (6-methoxy-1, 2, 3, 4-tetrahydronaphthalen-1-yl) -5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (Phenylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (azepan-1-ylcarbonyl) -N- (3-ethylbenzyl) -5-methylbenzamide {3- [ ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) methyl]Phenyl } carbamic acid methyl ester 5-oxo-L-prolyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -isobutyl-5-methylisophthalimide 4- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-4-oxo-3- { [ (1-propylbutyl) sulfonyl]Trifluoroacetic acid methyl ester N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ methyl (methylsulfonyl) amino]Benzamide derivatives

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ ethyl (isopropyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (2-thienyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (2-hydroxyethyl) (propyl) amino]Sulfonyl } propanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- { [ isopropyl (methyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorobenzeneYl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- [ (methylsulfonyl) amino group]-1, 3-thiazole-4-carboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ allyl (cyclopentyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (3-methylbutyl) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (5-methyl-2-thienyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (3-methoxyphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (1-methylhexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- ({ [1- (aminocarbonyl) cyclohexyl)]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2E) -hex-2-en-1-ylamino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (4-fluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-hydroxyisoxazole-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ (1E) -hex-1-en-1-yl)]Benzyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (isopropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (2-thienyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl [3- (2-amino-2-oxoethoxy) phenyl]Acetic acid ester (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methoxybenzyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2-ethylhexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (6-methoxypyridin-3-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (2, 4-dimethoxypyrimidin-5-yl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorobenzeneYl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-ethylbutanoyl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (4-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 4- [ 2' - (aminocarbonyl) biphenyl-4-yl ]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (3-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-hydroxy-1-phenylpropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ [2- (dimethylamino) ethyl](Ethyl) amino group]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-methyl-4H, 6H-pyrrolo [1, 2-a ]][4，1]Benzoxazepine-4-carboxylic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (5-acetyl-2-thienyl) acetate (1R, 2S) -2-amino-3- (3, 5-dichlorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropyl)Amino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (diisopropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (methylsulfonyl) amino group]Benzoic acid esters

(1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl [4- (2-oxopyrrolidin-1-yl) phenyl]Acetic acid ester (1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (1-methyl-1H-imidazol-4-yl) sulfonyl]Amino benzoate trihydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ (pentylamino) methyl group]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (4-fluorophenyl) -1- { [ (3-methoxybenzyl) ammoniaBase of]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- [ (benzylamino) methyl ]-3- (3-chloro-5-fluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3- { [ cyclohexyl (ethyl) amino]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [2- ({ [ (2, 4-difluorophenyl) amino]Carbonyl } oxy) ethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (2S) -2- (methoxymethyl) pyrrolidin-1-yl]Carbonyl } -5-methylbenzoate hydrochloride (1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 8-dimethylquinoline-3-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (6-hydroxyhexyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (2R) -2-hydroxypropyl { (2R))]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- [ (1-propylbutyl) sulfonyl]Propionic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (2-hydroxy-1, 1-dimethylethyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (4-phenylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 7- (1H-imidazol-1-yl) -5, 6-dihydronaphthalene-2-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (acetylamino) -4-methylbenzoate (1R, 2S) -2-amino-1- ({ [2- (aminosulfonyl) ethyl)]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [2- (ethylthio) ethyl) ]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3-cyclohexyl-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ benzyl (cyanomethyl) amino]Methyl } -3- (3, 5-difluorophenyl)) Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2-hydroxypropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-butoxypropyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [2- (2-hydroxyethyl) piperidin-1-yl]Carbonyl } -5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1-hydroxy-2-propylpentyl) benzoate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-chloro-5-fluorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 4- [ (methylsulfonyl) amino group]Butyrate trifluoroacetate salt (1R, 2S) -2-amino-1- ({ [3- (1-benzothien-2-yl) benzyl]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (benzyloxy) isoxazole-5-carboxylate (1R, 2S) -2-amino-1- { [ (cyclopropylmethyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine ester trifluoroacetate salt

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- (1H-pyrazol-1-yl) pentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1- (2-furylmethyl) -5-oxopyrrolidine-3-carboxylic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-ethylhexanoate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (5-hydroxypentyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]Piperidine-1-carboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (diethylamino) carbonyl group]Piperidine-1-carboxylic acid ester (1R, 2S) -2-amino-3- (pentafluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3-bromo-5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (methylsulfonyl) amino group]Benzoic acid esters (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (2-thienyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethoxypropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (2-thienyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 2-hydroxy-4- (phenylsulfonyl) butyrate hydrochloride (1R, 2S) -2-amino-3- (3, 5-dichlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethoxy) phenyl group]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-Ethyl-N- (3-ethylbenzyl) -N' -isopropyl-5-methylisophthalimide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2-hydroxyethyl) (propyl) amino]Sulfonyl propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N '-isopropyl-N', 5-dimethyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (methylsulfonyl) amino]-1, 3-thiazole-4-carboxamide N-allyl-N' - [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N-cyclopentyl-N' - (3-ethylbenzyl) -5-methyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (3-methylbutyl) sulfonyl]Propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [3- (5-methyl-2-thienyl) benzyl]-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (1-methylhexyl) -N ', N' -dipropyl-isophthalamide N- [1- (aminocarbonyl) cyclohexyl]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (2E) -hex-2-en-1-yl]-5-methyl-N ', N' -dipropyl-isophthalamide N-[(2R，3S)-3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-hydroxyisoxazole-5-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- {3- [ (1E) -hex-1-en-1-yl]Benzyl } -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -isopropyl-5-methyl-isophthalamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide 2- (3- {2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-iodobenzyl) amino]-2-oxoethyl } phenoxy) acetamide N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2-ethylhexyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (6-methoxypyridin-3-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (2, 4-dimethoxypyrimidin-5-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (2-ethylbutyryl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (4-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzamide N¹- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 4- [ 2' - (aminocarbonyl) biphenyl-4-yl]-4-oxobutanoic acid ester 1- (3- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -5-methylbenzoyl) -L-prolinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (3-hydroxypiperidin-1-yl) carbonyl]-5-methylbenzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-hydroxy-1-phenylpropyl) -5-methyl-N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [2- (dimethylamino) ethyl group]-N-ethyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-bis)Fluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-methyl-4H, 6H-pyrrolo [1, 2-a)][4，1]Benzoxazepine-4-carboxamides 2- (5-acetyl-2-thienyl) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) acetamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl ] -butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N ', N' -diisopropyl-5-methylisophthalimide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- [ (methylsulfonyl) amino]Benzamide derivatives N¹- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-iodobenzyl) -2- [4- (2-oxopyrrolidin-1-yl) phenyl]Acetamide N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N¹- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3,5-triamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (1-methyl-1H-imidazol-4-yl) sulfonyl]Amino benzamide trihydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N-pentyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-cyclohexyl-N' -ethyl-N- (3-ethylbenzyl) -5-methyl-isophthalamide 2- ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) ethyl (2, 4-difluorophenyl) carbamate N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2S) -2- (methoxymethyl) pyrrolidin-1-yl]Carbonyl } -5-methylbenzamide hydrochloride N¹- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N¹- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 8-dimethylquinoline-3-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (6-hydroxyhexyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (2R) -2-hydroxypropyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -3- [ (1-propylbutyl) sulfonyl]Propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2-hydroxy-1, 1-dimethylethyl) amino]Sulfonyl benzamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (4-phenylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-7- (1H-imidazol-1-yl) -N- (3-iodobenzyl) -5, 6-dihydronaphthalene-2-carboxamide 3- (acetylamino) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-methylbenzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [2- (aminosulfonyl) ethyl]-5-Aradical-N ', N' -dipropyl-m-phenylenediamine N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [2- (ethylthio) ethyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4-cyclohexyl-2-hydroxybutyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2-hydroxypropyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-butoxypropyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [2- (2-hydroxyethyl) piperidin-1-yl]Carbonyl } -5-methylbenzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- {3- [ (dipropylamino) carbonyl]-5-methylbenzoyl } -beta-alanine methyl ester N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (1-hydroxy-2-propylpentyl) benzamide N¹- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- [ (methylsulfonyl) amino]Butyramide trifluoroacetate salt N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (1-benzothien-2-yl) benzyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (benzyloxy) -N- (3-ethylbenzyl) isoxazole-5-carboxylic acid amide 1- (3- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -5-methylbenzoyl) -D-prolinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (1H-pyrazol-1-yl) pentanamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1- (2-furylmethyl) -5-oxopyrrolidine-3-carboxamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-ethyl-N- (3-methoxybenzyl) hexanamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (5-hydroxypentyl) -5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylpiperidine-1, 3-dicarboxamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N³，N³-diethyl-N¹- (3-methoxybenzyl) piperidine-1, 3-dicarboxamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (pentafluorophenyl) butyl]-5-bromo-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- [ (methylsulfonyl) amino]Benzamide derivatives N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl ]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethoxypropyl) -5-methyl-N ', N' -dipropyl-m-phenylenediamine N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4- (phenylsulfonyl) butanamide hydrochloride N¹- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl ] -butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3)3-dimethylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-bromophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl ]Benzoic acid esters (1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (1, 3-diphenylpropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -1- (hydroxymethyl) propyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (3S) -2-oxoazepan-3-yl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- (cyclohexylamino) -5-oxopentanoate (1R, 2S) -2-amino- {1- [ (3-methoxybenzyl) amino]Methyl } -3- (3-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (2-propylpentylsulfonyl)]-beta-alanine ester trifluoroacetate salt (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (1, 3-thiazol-2-yl) benzoate dihydrochloride (1R, 2S) -2-amino-3- (2-furyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({3- [ methyl (phenyl) amino)]Propyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-1- (2-thienylmethyl) pyrrolidine-3-carboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (butylthio) methyl group]-5-methyl-2-furoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (2-hydroxyethyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [3- (trifluoromethyl) benzoyl]Glycine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylcyclohexyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-(2-oxo-1, 3-oxazolidin-3-yl) benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1H-pyrrol-1-yl) benzoate

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (6-methoxy-1, 2, 3, 4-tetrahydronaphthalen-1-yl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1, 3, 4, 5-tetrahydrothiopyrano [4, 3-b ]]Indole-8-carboxylic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4- { [2- (trifluoromethyl) phenyl]Amino butyrate (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4, 5-dimethyl-2- (1H-pyrrol-1-yl) thiophene-3-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2, 3-dihydroxypropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (2S) -2-hydroxypropyl { (2S))]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-Ammonia3- (3, 5-difluorophenyl) -1- ({ [ (1R) -1-methylpropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-chloro-4- (methylsulfonyl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2-hydroxyethyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (3-methoxyphenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { methyl [ (trifluoromethyl) sulfonyl group]Amino benzoate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3-hydroxy-6- (1-hydroxy-2, 2-dimethylpropyl) pyridine-2-carboxylate (1R, 2S) -2-amino-1- { [ (1, 3-dicyclohexylpropyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 2' -bithiophene-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1H-imidazol-1-yl) butanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 3-dihydroxy-4- [ (4-methoxyphenyl) amino]-4-oxobutanoic acid ester

(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-hydroxyphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (2-thienyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- ({ [2- (aminocarbonyl) -1H-indol-6-yl ]Amino } methyl) -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-bromophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [4- (trifluoromethyl) benzoyl]Glycine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1-oxo-1, 3-dihydro-2H-isoindol-2-yl) butanoate (1R, 2S) -2-amino-3- (3, 5-fluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3, 4-dichlorobenzoyl) glycine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-chloro-4- (methylsulfonyl)) Thiophene-2-carboxylic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (1-ethylpropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({ [ (5R) -3-ethyl-2-oxo-1, 3-oxazolidin-5-yl)]Methyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methyl-7- (trifluoromethyl) pyrazolo [1, 5-a]Pyrimidine-2-carboxylic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (methylthio) acetyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2, 3-dimethylcyclohexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4, 5-dimethoxy-1-benzothiophene-2-carboxylate (1R, 2S) -2-amino-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({ [ (5S) -3-ethyl-2-oxo-1, 3-oxazolidin-5-yl)]Methyl } amino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl ]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 5-dioxo-1, 2, 4-triazolidin-4-yl) benzoate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (3-methoxyphenyl) sulfonyl group]Propionic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (2-methylcyclohexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (2- {4- [ (3-chlorobenzyl) oxy ] oxy]Phenyl } ethyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4-oxo-4- (3-thienyl) butanoic acid ester (1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4-oxo-4- [3- (trifluoromethyl) phenyl]Butyric ester (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino ]Methyl } -3- [3- (trifluoromethoxy) phenyl group]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (hydroxymethyl) -3- (methylthio) propyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1H-1, 2, 3-benzotriazol-1-yl) hexanoate ester (1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [ (trifluoromethyl) sulfonyl]Amino } butanoate trifluoroacetate salt (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (5-methyl-1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-hydroxypropyl) amino ]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (hydroxymethyl) propyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-1- [ (benzylamino) methylBase of]-3- (3, 5-dichlorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- { [ (2-hydroxyethyl) (propyl) amino]Sulfonyl propionate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 5- (benzylthio) nicotinate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1H-pyrazole-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-chloro-3-methyl-2-oxo-2, 3-dihydro-1, 3-benzoxazole-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1H-benzimidazole-2-carboxylate (1R, 2S) -2-amino-3-cyclohexyl-1- { [ (3-methoxybenzyl) amino ]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-hydroxy-4, 7-dimethoxy-1-benzofuran-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (4-methylcyclohexyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl [1, 2, 4 ]]Triazolo [4, 3-a]6-Pyridinecarboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4-oxo-4- (2-thienyl) butanoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3, 5-dichlorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2-hydroxy-5-methylphenyl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 3-phenoxybenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 4- [ (aminocarbonyl) amino]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -1- (hydroxymethyl) -3- (methylthio) propyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 7-hydroxy-4-oxochroman-2-carboxylate

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -1- (hydroxymethyl) -3-methylbutyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -1- (hydroxymethyl) propyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (1-methyl-3-phenylpropyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3, 3-dimethylbutyl) -5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl ]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (1, 3-diphenylpropyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1S) -1- (hydroxymethyl) propyl group]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [ (3S) -2-oxoazepan-3-yl]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' -cyclohexyl-N- (3-ethylbenzyl) glutaramide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N³- [ (2-Propylpentyl) sulfonyl group]-beta-alanine amide trifluoroacetate salt N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (1, 3-thiazol-2-yl) benzamide dihydrochloride N- [ (2R, 3S) -3-amino-4- (2-furyl) -2-hydroxybutyl ]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- {3- [ methyl (phenyl) amino]Propyl } -N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-oxo-1- (2-thienylmethyl) pyrrolidine-3-carboxamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- [ (butylthio) methyl group]-N- (3-ethylbenzyl) -5-methyl-2-furoamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (2-hydroxyethyl) amino]Sulfonyl benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylcyclohexyl) -N ', N' -dipropylMetaphenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-oxo-1, 3-oxazolidin-3-yl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -4- (1H-pyrrol-1-yl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (6-methoxy-1, 2, 3, 4-tetrahydronaphthalen-1-yl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1, 3, 4, 5-tetrahydrothiopyrano [4, 3-b]Indole-8-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - [2- (trifluoromethyl) phenyl]Succinic acid amides N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4, 5-dimethyl-2- (1H-pyrrol-1-yl) thiophene-3-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2, 3-dihydroxypropyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (2S) -2-hydroxypropyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-) Difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [ (1R) -1-methylpropyl group]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2-chloro-N- (3-ethylbenzyl) -4- (methylsulfonyl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2-hydroxyethyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { methyl [ (trifluoromethyl) sulfonyl ] sulfonyl]Amino benzamide hydrochloride

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-hydroxy-6- (1-hydroxy-2, 2-dimethylpropyl) pyridine-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (1, 3-dicyclohexylpropyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 2' -bithiophene-5-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (1H-imidazol-1-yl) butanamide N- [ (2R, 3S) -3-amino-4- (3, 5-bis)Fluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 3-dihydroxy-N' - (4-methoxyphenyl) succinamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N¹- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [2- (aminocarbonyl) -1H-indol-6-yl]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (1-oxo-1, 3-dihydro-2H-isoindol-2-yl) butanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-3-chloro-N- (3-ethylbenzyl) -4- (methylsulfonyl) thiophene-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (1-ethylpropyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- { [ (5R) -3-ethyl-2-oxo-1, 3-oxazolidin-5-yl]Methyl } -5-methyl-N ', N' -dipropyl-m-phenylenediamine N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-methyl-7- (trifluoromethyl) pyrazolo [1, 5-a]Pyrimidine-2-carboxamides N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -N²- [ (methylthio) acetyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine amide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2, 3-dimethylcyclohexyl) -5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4, 5-dimethoxy-1-benzothiophene-2-carboxamide N¹- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- { [ (5S) -3-ethyl-2-oxo-1, 3-oxazolidin-5-yl]Methyl } -5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutanBase of]-4- (3, 5-dioxo-1, 2, 4-triazolidin-4-yl) -N- (3-ethylbenzyl) benzamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (3-methoxyphenyl) sulfonyl]Propionamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (2-methylcyclohexyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (2- {4- [ (3-chlorobenzyl) oxy)]Phenyl } ethyl) -5-methyl-N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4-oxo-4- (3-thienyl) butanamide N¹- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl ]-2-hydroxybutyl } -N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4-oxo-4- [3- (trifluoromethyl) phenyl]Butylamide N¹- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (hydroxymethyl) -3- (methylthio) propyl group]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxyButyl radical]-2- (1H-1, 2, 3-benzotriazol-1-yl) -N- (3-ethylbenzyl) hexanamide N¹- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- { [ (trifluoromethyl) sulfonyl ]Amino } butanamide trifluoroacetate salt

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (5-methyl-1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-hydroxypropyl) -5-methyl-N ', N' -dipropyl isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [1- (hydroxymethyl) propyl]-5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl ] -butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- { [ (2-hydroxyethyl) (propyl) amino]Sulfonyl radical} -N- (3-methoxybenzyl) propanamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5- (benzylsulfanyl) -N- (3-ethylbenzyl) nicotinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1H-pyrazole-5-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-chloro-N- (3-ethylbenzyl) -3-methyl-2-oxo-2, 3-dihydro-1, 3-benzoxazole-5-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1H-benzimidazole-2-carboxamide N¹- [ (2R, 3S) -3-amino-4-cyclohexyl-2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -6-hydroxy-4, 7-dimethoxy-1-benzofuran-5-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (4-methylcyclohexyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) [1, 2, 4 ]]Triazolo [4, 3-a]Pyridine-6-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4-oxo-4- (2-thienyl) butanamide N- [ (2R, 3S) -3-amino-4- (3, 5-dichlorobenzene)2-hydroxybutyl radical]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-hydroxy-5-methylphenyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -3-phenoxybenzamide

4- [ (aminocarbonyl) amino group]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1S) -1- (hydroxymethyl) -3- (methylthio) propyl group]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -7-hydroxy-4-oxochroman-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1S) -1- (hydroxymethyl) -3-methylbutyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -1- (hydroxymethyl) propyl group]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- (1-methyl-3-phenylpropyl) -N ', N' -dipropyl isophthalamide (1R, 2S) -2-amino-3- (3, 5-difluoro)Phenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (2, 3-dihydro-1-benzofuran-5-yl) -1, 3-thiazole-4-carboxylate (1R, 2S) -2-amino-3- [3- (benzyloxy) phenyl ]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl radical]Propyl 3-oxo-3- (pentylamino) propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (trifluoromethoxy) benzoate (1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [4- (acetylamino) phenyl]Amino } -4-oxobutanoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1-cyanoethyl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4- [ (5-phenyl-1, 3, 4-thiadiazol-2-yl) amino]Butyric ester

(1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (trifluoromethoxy) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [2- (2-oxo-2-pyrrolidin-1-ylethoxy) phenyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (1, 1-dioxotetrahydro-2-thienyl) acetate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-chlorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 5-hex-1-yn-1-yl nicotinate (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methoxyisoxazole-5-carboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 3-dimethyl-1H-indole-7-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3-chlorophenyl) -2-hydroxy-4-oxobutanoate (1R, 2S) -2-amino-3- (3-fluoro-4-methoxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (1-methyl-1H-indol-3-yl) (oxo) acetate (1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (4-methylphenyl) propyl 3- [ (dipropylamino) sulfonyl group ]Propionic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-fluoro-4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [5- (4-methylphenyl) -2H-tetrazol-2-yl]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-dichlorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester

(1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (2-thienyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methyl-3-phenylisoxazole-4-carboxylic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-fluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (methylsulfonyl) acetyl]-N-pentyl glycinate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (4-methoxybenzoyl) glycine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2, 6-difluorobenzoyl) glycine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1H-indol-3-yl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (5-benzyl-1, 3, 4-thiadiazol-2-yl) amino]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3-fluoro-4-methoxyphenyl) -4-oxobutanoate 4- { [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2- ({3- [ (dipropylamino) -amino) Carbonyl radical]-5-methylbenzoyl } oxy) butyl]Amino } piperidine-1-carboxylic acid ethyl ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2-fluorobenzoyl) -1H-pyrrole-2-carboxylate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-chlorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl ]Benzoic acid esters (1R, 2S) -2-amino-3- (4-hydroxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (4-morpholin-4-ylphenyl) acetate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethoxy) phenyl group]Propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ benzyl (1-cyclopropylethyl) amino]-4-oxobutanoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (2, 5-dimethylbenzoyl) -5-methylbenzoate (1R, 2S) -2-amino-3- (3, 5-bis)Fluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (2-methoxy-5-methylphenyl) amino]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3-hydroxyphenyl) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ hydroxy (2-methylphenyl) methyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 5- (ethylthio) nicotinate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [4- (2-furoyl) piperazin-1-yl]-4-oxobutanoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-fluoro-4-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-oxoisoindoline-1-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (ethylthio) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl thieno [2, 3-b]Quinoline-2-carboxylic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4-methyl-1, 3-oxazol-2-yl) benzoate hydrochloride (1R, 2S) -2-amino-1- [ (benzyl)Arylamino) methyl groups]-3- (4-fluorophenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 2- [ 2-furoyl (methyl) amino group]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4- (3-methoxyphenyl) -4-oxobutanoate (1R, 2S) -2-amino-1- [ (cycloheptylamino) methyl]-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3-fluoro-5-hydroxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester hydrochloride

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-hydroxy-1H-indole-2-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 2-dimethylchroman-8-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-benzylpyrazine-2-carboxylate 4-oxide (1R, 2S) -2-amino-3- (3, 5-difluoro)Phenyl) -1- { [ (3-methoxybenzyl) amino ]Methyl } propyl {2- [ (dipropylamino) sulfonyl group]Ethyl carbamate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (hydroxymethyl) -2-methylpropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-chloro-5-fluorophenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (4-methoxyphenyl) -4-oxobutanoate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-hydroxyphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-4-oxo-3, 4-dihydrophthalazine-1-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3, 4-dihydro-2H-1, 5-benzodioxan-7-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [4- (2, 5-dioxopyrrolidin-1-yl) phenoxy]Acetic acid ester (1R, 2S) -2-amino-3- (2-furyl) -1- { [ (3-methoxybenzyl) amino ]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methyl-4-oxo-3, 4-dihydrothieno [2, 3-d]Pyrimidine-6-carboxylic acid esters (1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3-chloro-5-fluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 5- (dipropylamino) -5-oxopentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-fluoro-2-hydroxyquinoline-4-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4- (2-thienyl) butanoic acid ester

(1R, 2R) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (phenylthio) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -1- (hydroxymethyl) -2-methylpropyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R, 2S) -1- (hydroxymethyl) -2-methylbutyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (phenoxymethyl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 5- [ (2, 4-difluorophenyl) amino]-5-oxopentanoate ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- [ (4, 6-dimethylpyrimidin-2-yl) amino]-5-oxopentanoate ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (3-methoxybenzoyl) -5-methylbenzoate (1R, 2S) -2-amino-3- [3- (benzyloxy) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-dichlorophenyl) -4-oxobutanoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [4- (methoxycarbonyl) phenyl ]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- [ (4-acetylphenyl) amino]-5-oxopentanoate ester (1R, 2S) -2-amino-3- [4- (benzyloxy) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2R) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (phenylthio) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- ({2- [ (methylamino) carbonyl group]Phenyl } thio) propanoates (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- [ (1-propylbutyl) thio]Propionic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (4-ethoxyphenyl) amino]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [2- ({ [ (3-methoxyphenyl) amino) ]Carbonyl } oxy) ethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (2, 3-dihydro-1-benzofuran-5-yl) -N- (3-ethylbenzyl) -1, 3-thiazole-4-carboxamide N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) phenyl]-2-hydroxybutyl } -N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -pentylmalonamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (trifluoromethoxy) benzamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide N' - [4- (acetylamino) phenyl]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (1-cyanoethyl) -N- (3-ethylbenzyl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - (5-phenyl-1, 3, 4-thiadiazol-2-yl) succinamide N¹- (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [2- (2-oxo-2-pyrrolidin-1-ylethoxy) phenyl]-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (1, 1-dioxotetrahydro-2-thienyl) -N- (3-ethylbenzyl) acetamide N- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl ]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-hex-1-yn-1-ylnicotinamide N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-methoxyisoxazole-5-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 3-dimethyl-1H-indole-7-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3-chlorophenyl) -N- (3-ethylbenzyl) -2-hydroxy-4-oxobutanamide N¹- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methoxyphenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (1-methyl-1H-indol-3-yl) -2-oxoacetamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N¹- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [5- (4-methylphenyl) -2H-tetrazol-2-yl]Acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-methyl-3-phenylisoxazole-4-carboxamide N- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- [ (methylsulfonyl) acetyl group]-N²-pentyl glycinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -4- (1H-indol-3-yl) -4-oxobutanamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (5-benzyl-1, 3, 4-thiadiazol-2-yl) -N- (3-ethylbenzyl) succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (3-fluoro-4-methoxyphenyl) -4-oxobutanamide 4- ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) piperidine-1-carboxylic acid ethyl ester N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-fluorobenzoyl) -1H-pyrrole-2-carboxamide N¹- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N¹- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (4-morpholin-4-ylphenyl) acetamide N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N '-benzyl-N' - (1-cyclopropylethyl) -N- (3-ethylbenzyl) succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (2, 5-dimethylbenzoyl) -N- (3-methoxybenzyl) -5-methylbenzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - (2-methoxy-5-methylphenyl) succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (3-hydroxyphenyl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- [ hydroxy (2-methylphenyl) methyl]-N- (3-methoxybenzyl) -5-methylbenzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5- (ethylsulfanyl) nicotinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- [4- (2-furoyl) piperazin-1-yl]-4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-bis)Fluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-oxoisoindoline-1-carboxylic acid amide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (ethylsulfanyl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) thieno [2, 3-b]Quinoline-2-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (4-methyl-1, 3-oxazol-2-yl) benzamide hydrochloride N¹- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- (2- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } phenyl) -N-methyl-2-furoamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4- (3-methoxyphenyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N-cycloheptyl-5-methyl-N ', N' -dipropyl isophthalamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-5-hydroxyphenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propionamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-hydroxy-1H-indole-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 2-dimethylchroman-8-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-benzyl-N- (3-ethylbenzyl) pyrazine-2-carboxamide 4-oxide 2- ({ [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-methoxybenzyl) amino]Carbonyl } amino) -N, N-dipropylethanesulfonamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -1- (hydroxymethyl) -2-methylpropyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N-benzyl-3- [ (dipropylamino) sulfonyl group ]Propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (4-methoxyphenyl) -4-oxobutanamide

N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-methyl-4-oxo-3, 4-dihydrophthalazine-1-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3, 4-dihydro-2H-1, 5-benzodioxan-7-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- [4- (2, 5-dioxopyrrolidin-1-yl) phenoxy]-N- (3-ethylbenzyl) acetamide N¹- [ (2R, 3S) -3-amino-4- (2-furyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-methyl-4-oxo-3, 4-dihydrothieno [2, 3-d]Pyrimidine-6-carboxamides N¹- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3-chloro-5-fluorophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -6-fluoro-2-hydroxyquinoline-4-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-oxo-4- (2-thienyl) butanamide N³- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-methoxybenzyl) amino]Carbonyl group } -N¹，N¹-dipropyl-beta-alaninamide N¹- [ (2R, 3R) -3-amino-2-hydroxy-4- (phenylthio) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -1- (hydroxymethyl) -2-methylpropyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R, 2S) -1- (hydroxymethyl) -2-methylbutyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (phenoxymethyl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N' - (2, 4-difluorophenyl) -N- (3-ethylbenzyl) glutaramide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (4, 6-dimethylpyrimidin-2-yl) -N- (3-ethylbenzyl) glutaramide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (3-methoxybenzoyl) -N- (3-methoxybenzyl) -5-methylbenzamide N¹- { (2R, 3S) -3-amino-4- [3- (benzyloxy) phenyl]-2-hydroxybutyl } -N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dichlorophenyl) -N- (3-ethylbenzyl) -4-oxobutanamide 4- { (2S, 3R) -2-amino-4- [ {3- [ (dipropylamino) carbonyl]-5-methylbenzoyl } (3-methoxybenzyl) amino]-3-hydroxybutyl } benzoic acid methyl ester N' - (4-acetylphenyl) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) glutaramide N- { (2R, 3S) -3-amino-4- [4- (benzyloxy) phenyl]-2-hydroxybutyl } -N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3R) -3-amino-2-hydroxy-4- (phenylthio) butyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide 2- ({3- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-3-oxopropyl } thio) -N-methylbenzamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -3- [ (1-propylbutyl) thio]Propionamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (4-ethoxyphenyl) -N- (3-ethylbenzyl) succinamide N¹- (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide 2- ([ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]{3- [ (dipropylamino) carbonyl group]-5-methylbenzoyl } amino) ethyl (3-methoxyphenyl) carbamate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (benzyloxy) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -2-hydroxy-1-methylethyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (pentafluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (4-hydroxyphenyl) -4-oxobutanoate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (piperidin-3-ylsulfonyl) benzoate dihydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 6-chloro-4-hydroxyquinoline-2-carboxylate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (2-thienyl) propyl 5- (dipropylamino) -5-oxopentanoate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -4-methylpentyl 3- [ (dipropylamino) carbonyl group]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (6-oxo-3-phenylpyridazin-1 (6H) -yl) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- {4- [ (methylsulfonyl) amino group]Phenyl } propanoate (1R, 2S) -2-amino-3- (4-fluoro-3-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 3- (2-chlorophenoxy) propionate (1R, 2S) -2-amino-3- (4-fluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (4-chlorobenzoyl) -D-alanine ester (1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (4-methylphenyl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4- { [3- (trifluoromethyl) phenyl ]Amino butyrate (1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (5-pyridin-2-yl-2H-tetrazol-2-yl) acetate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (3-methylphenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl isoxazole-5-carboxylic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3, 5-dimethoxyphenoxy) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2, 5-dimethyl-1H-pyrrol-1-yl) -3-hydroxybenzoates (1R, 2S) -2-amino-3- (3-bromophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 5- (dipropylamino) -5-oxopentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [5- (cyclopentylmethyl) -1, 3, 4-thiadiazol-2-yl ]Amino } -4-oxobutanoic acid esters (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonylBase of]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3-oxo-1, 2-benzisothiazol-2 (3H) -yl) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ 1-methyl-5- (pyrrolidin-1-ylcarbonyl) -1H-pyrrol-3-yl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-difluorophenyl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2-naphthyl) -4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4, 6-diethoxypyridine-2-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (5-methyl-1H-pyrrol-2-yl) -4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- ({ [2- (methylamino) ethyl]Amino } sulfonyl) benzoate hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3-methyl-5- (4-methylbenzoyl) benzoate (1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- [ (benzylamino) methyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (piperazin-1-ylsulfonyl) benzoate hydrochloride (1R, 2S) -2-amino-1- [ ({2- [4- (aminosulfonyl) phenyl)]Ethyl } amino) methyl]-3- (3, 5-difluorophenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ 2-hydroxy-1- (hydroxymethyl) ethyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (4-fluoro-3-methylphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (3-oxo-2, 1-benzisothiazol-1 (3H) -yl) propanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2, 6-dihydroxypyrimidin-4-yl) acetate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 5- (dipropylamino) -5-oxopentanoate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-hydroxyphenyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-difluorophenyl) -2-methyl-4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-5- [ (2-pyridin-2-ylethyl) amino]Valeric acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [2- (4-fluorophenyl) -1, 3-benzoxazol-5-yl]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenylaminocarbonyl) glycinate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2, 6-dimethoxybenzoyl) glycinate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1, 3-dithiane-2-yl) -3-furoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- [ 2-oxo-2- (propylamino) ethyl]Benzoic acid esters (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-bromophenyl) propyl 3- [ (dipropylamino) sulfonyl]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl 3- (2-fluorophenyl) propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-methylthiophene-2-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl } propyl [4- (benzyloxy) phenyl]Acetic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl [ (5, 7-dimethyl [1, 2, 4 ]]Triazolo [4, 3-a]Pyrimidin-3-yl) thio groups]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (1-acetyl-2, 3-dihydro-1H-indol-7-yl) amino]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 5- [ (3-acetylphenyl) amino]-5-oxopentanoate ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4-chlorophenoxy) -2-hydroxypropionate N³- [ (1S, 2R) -3- (benzylamino) -1- (3-fluoro-4-methoxybenzyl) -2-hydroxypropyl]-N¹，N¹-dipropylbenzene-1, 3, 5-trimethylamide (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1H-indole-7-carboxylate (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (3-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1, 2, 3-thiadiazol-4-yl) benzylAcid esters (1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl ]Methyl propionate (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (4-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ 1-methyl-3- (methylthio) -1H-indol-2-yl]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-dichlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (2- { [4- (1, 3-oxazol-5-yl) phenyl [ ]]Amino } -2-oxoethyl) thio]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2-furyl) -4-oxobutanoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (3-pyridin-2-yl-1, 2, 4-oxadiazol-5-yl) propanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl [2- (acetylamino) -1, 3-thiazol-4-yl]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (4-methyl-4H-1, 2, 4-triazol-3-yl) thio group](phenyl) acetic acid ester (1R, 2S) -2-amino-3- (4-chlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (1, 3-benzothiazol-2-yl) butanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (3-chloro-4-fluorophenyl) amino group]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (2-oxo-2, 3-dihydroquinazolin-4-yl) thio group]Acetic acid ester N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (benzyloxy) -N- (3-ethylbenzyl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- [ (1S) -2-hydroxy-1-methylethyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (pentafluorophenyl) butyl]-5-methyl-N ', N' -dipropyl-N- [3- (trifluoromethyl) benzyl]M-phenylene diamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (4-hydroxyphenyl) -4-oxobutanamide N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (piperidin-3-ylsulfonyl) benzamide dihydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-chloro-N- (3-ethylbenzyl) -4-hydroxyquinoline-2-carboxamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide N- [ (2R, 3S) -3-amino-2-hydroxy-5-methylhexyl]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (6-oxo-3-phenylpyridazin-1 (6H) -yl) acetamide N- (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- {4- [ (methylsulfonyl) amino]Phenyl propanamide N¹- [ (2R, 3S) -3-amino-4- (4-fluoro-3-methylphenyl) -2-hydroxybutyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (2-chlorophenoxy) -N- (3-iodobenzyl) propanamide N¹- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propionamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (4-methylphenyl) -4-oxobutanamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-oxo-4- { [3- (trifluoromethyl) phenyl]Amino butyrate N- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl ]-N- (3-methoxybenzyl) -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethyl)Benzyl) isoxazole-5-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (3, 5-dimethoxyphenoxy) -N- (3-ethylbenzyl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (2, 5-dimethyl-1H-pyrrol-1-yl) -N- (3-ethylbenzyl) -3-hydroxybenzamide N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - [5- (cyclopentylmethyl) -1, 3, 4-thiadiazol-2-yl]-N- (3-ethylbenzyl) succinamide N¹- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (3-oxo-1, 2-benzisothiazol-2 (3H) -yl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-methyl-N- [ 1-methyl-5- (pyrrolidin-1-ylcarbonyl) -1H-pyrrol-3-yl]-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-difluorophenyl) -N- (3-ethylbenzyl) -4-oxobutanamide N-[(2R，3S)-3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-naphthyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4, 6-diethoxy-N- (3-ethylbenzyl) pyridine-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (5-methyl-1H-pyrrol-2-yl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- ({ [2- (methylamino) ethyl)]Amino } sulfonyl) benzamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -3-methyl-5- (4-methylbenzoyl) benzamide N- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (piperazin-1-ylsulfonyl) benzamide hydrochloride N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- {2- [4- (aminosulfonyl) phenyl]Ethyl } -5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ 2-hydroxy-1- (hydroxymethyl) ethyl]-5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-4- (4-fluoro-3-methylphenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (3-oxo-2, 1-benzisothiazol-1 (3H) -yl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (2, 6-dihydroxypyrimidin-4-yl) -N- (3-ethylbenzyl) acetamide N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-N-benzyl-3- [ (dipropylamino) sulfonyl group ]Propionamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-difluorophenyl) -N- (3-ethylbenzyl) -2-methyl-4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - (2-pyridin-2-ylethyl) glutaramide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [2- (4-fluorophenyl) -1, 3-benzoxazol-5-yl]Acetamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- (phenylaminocarbonyl) -N¹- (3-ethylbenzyl) glycinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (1, 3-dithiane-2-yl)) -N- (3-ethylbenzyl) -3-furoamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ 2-oxo-2- (propylamino) ethyl]Benzamide derivatives N- [ (2R, 3S) -3-amino-4- (3-bromophenyl) -2-hydroxybutyl]-N-benzyl-3- [ (dipropylamino) sulfonyl group]Propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (2-fluorophenyl) -N- (3-iodobenzyl) propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -5-methylthiophene-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- [4- (benzyloxy) phenyl]-N- (3-iodobenzyl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- [ (5, 7-dimethyl [1, 2, 4 ]]Triazolo [4, 3-a]Pyrimidin-3-yl) thio groups]-N- (3-ethylbenzyl) acetamide N' - (1-acetyl-2, 3-dihydro-1H-indol-7-yl) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) succinamide N' - (3-acetylphenyl) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) glutaramide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4-chlorophenoxy) -N- (3-ethylbenzyl) -2-hydroxypropionamide N³- [ (1S, 2R) -3- (benzylamino) -1- (3-fluoro-4-methoxybenzyl) -2-hydroxypropyl]-N¹，N¹-dipropylbenzene-1, 3, 5-trimethylamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1H-indole-7-carboxamide

N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (1, 2, 3-thiadiazol-4-yl) benzamide N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-5-methyl-N- (3-methylbutyl-N ', N' -dipropyl-isophthalamide N- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ 1-methyl-3- (methylthio) -1H-indol-2-yl]Acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide 2- ({2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-2-oxoethyl } thio) -N- [4- (1, 3-oxazol-5-yl) phenyl]Acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (2-furyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (3-pyridin-2-yl-1, 2, 4-oxadiazol-5-yl) propanamide 2- [2- (acetylamino) -1, 3-thiazol-4-yl ] -2]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (4-methyl-4H-1, 2, 4-triazol-3-yl) thio]-2-phenylacetamide N- [ (2R, 3S) -3-amino-4- (4-chlorophenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (1, 3-benzothiazol-2-yl) -N- (3-ethylbenzyl) butanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N' - (3-chloro-4-fluorophenyl) -N- (3-ethylbenzyl) succinamide N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (2-oxo-2, 3-dihydroquinazolin-4-yl) thio]Acetamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3-methyl-5- (2-methylbenzoyl) benzoate (1R, 2S) -2-amino-3- (4-hydroxyphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 5- (dipropylamino) -5-oxopentanoate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (4-methylphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 4-propoxybenzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1-methyl-1H-indole-2-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-chloro-2- (3-methyl-4H-1, 2, 4-triazol-4-yl) benzoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-difluorophenyl) -2-methoxy-4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [3- (2-thienyl) -1H-pyrazol-1-yl]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-phenylamino-5-oxopentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2-thio-1, 3-benzothiazol-3 (2H) -yl) acetate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3-Cyclohexylpropyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3- (4-methoxyphenyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3-hydroxy-4-methylphenyl) acetate (1R, 2S) -2-amino-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 7-fluoro-4H-imidazo [5, 1-c][1，4]Benzoxazine-3-carboxylic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-dihydro-2H-1, 5-benzodioxan-7-yl) -4-oxobutanoate

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 1-benzofuran-3-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (3, 4-dichlorophenyl) amino group]-3-oxopropionic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -2-hydroxy-1-methylethyl)]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-methylphenyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 5-oxo-5- (pyridin-3-ylamino) pentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-methyl-4-oxo-4H-benzopyran-6-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl ({2- [ (5-methylisoxazol-3-yl) amino]-2-oxoethyl } thio) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (1H-imidazol-1-yl) propyl]Amino } methyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R，2S) -2-amino-3- [ 3-fluoro-5- (trifluoromethyl) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (4-hydroxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- (2-thienyl) propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 4- [ (2, 2-dimethylpropanoyl) amino]-2-hydroxybenzoates (1R, 2S) -2-amino-3- (3-methoxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (4-fluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- { [ (3-methoxybenzyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- [3- (trifluoromethyl) phenyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 6- (2-furoylamino) hexanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (1-phenyl-4, 5-dihydro-1H-tetrazol-5-yl) thio]Acetic acid ester (1S, 2S) -2-amino-3-phenyl-1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- { [ (3-methoxybenzyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-dihydro-2H-benzopyran-6-yl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3-methoxyphenyl) -1- { [ (3-methylbutyl) amino ]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3-fluoro-4-methylphenyl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 5- (dipropylamino) -5-oxopentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl indolizine-2-carboxylate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (trifluoromethoxy) phenyl]Propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl nicotinate 1-oxide (1R, 2S) -2-amino-3- [3- (benzyloxy) -5-fluorophenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-iodobenzyl) amino]Methyl propyl [ (aminocarbonyl) oxy group]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2, 3-dihydro-1H-cyclopenta [ b]Quinoline-9-carboxylic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3-methyl-1H-pyrazole-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- (benzoylamino) pentanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (methoxymethyl) thio group]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1, 3-benzothiazol-2-yl) -3-methoxypropionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- { [ (methylamino) carbonyl]Amino } -3- (3-thienyl) propionic acid esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-pyridin-2-ylthiophene-2-carboxylate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- [3- (benzyloxy) -5-fluorophenyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (5, 6-dimethyl-2, 4-dioxo-1, 2, 3, 4-tetrahydropyridin-3-yl) acetate (1R, 2S) -2-amino-3- (3-fluoro-4-methoxyphenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) carbonyl ]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-isobutyl-1, 3-dioxoisoindoline-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5- (acetylamino) -2-furoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (4-methoxyphenyl) acetyl]Glycine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propylisoquinoline-4-carboxylate (1R, 2S) -2-amino-3- [3- (benzyloxy) phenyl]-1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (4-hydroxy-3-methoxyphenyl) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (4-phenyl-4H-1, 2, 4-triazol-3-yl) thio]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (3, 5-dimethoxyphenyl) acetate (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (3-methoxyphenyl) propyl 3- [ (dipropylamino) carbonylBase of]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2-ethyl-4H- [1, 2, 4)]Triazolo [1, 5-a]Benzimidazol-4-yl) acetic acid esters (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (2-furyl) propyl 3- [ (dipropylamino) carbonyl]-5-methylbenzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 7-chloro-1-benzofuran-2-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) propionate

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-oxo-2H-1, 3-benzoxazin-3 (4H) -yl) propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (pyrimidin-2-ylthio) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- { [3- (aminocarbonyl) -4, 5, 6, 7-tetrahydro-1-benzothien-2-yl ]Amino } -4-oxobutanoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (5-phenyl-1, 3, 4-oxadiazol-2-yl) thio]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-bis)Fluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl quinoline-6-carboxylic acid ester (1R, 2S) -2-amino-1- [ (benzylamino) methyl]-3- (2-furyl) propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (2, 3-dihydro-1, 4-benzodioxine-6-yl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (1H-indol-3-yl) -1H-pyrazole-5-carboxylate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4- { [ (methylamino) thiocarbonyl]Amino } benzoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl 6-chloronicotinate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3-hydroxyphenyl) -4-oxobutanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (phthalazin-1-ylthio) acetate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl [ (1-oxidopyridin-2-yl) thio]Acetic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (acetylamino) -5-fluoro-1H-indole-2-carboxylate (1S, 2S) -2-amino-3-phenyl-1- ({ [3- (Tri-S) ]Fluoromethyl) benzyl]Amino } methyl) propyl 3- { [ (3-chlorobenzyl) amino]Sulfonyl benzoate esters (1R, 2S) -2-amino-3- [4- (benzyloxy) phenyl]-1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters (1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- [ (benzylamino) methyl]Propyl 3- (aminocarbonyl) -5- [ (dipropylamino) carbonyl]Benzoic acid esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- (3, 4-dichlorophenyl) -2-hydroxy-3-methyl-4-oxobutanoic acid ester (1R, 2S) -2-amino-1- { [ (3-methylbutyl) amino]Methyl } -3- [3- (trifluoromethoxy) phenyl group ]Propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (5-methyl-1, 3, 4-thiadiazol-2-yl) amino]-4-oxobutanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2-ethyl-1H-benzimidazol-1-yl) acetate (1R, 2S) -2-amino-3- (1, 3-benzodioxol-5-yl) -1- { [ (3-methoxybenzyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-oxo-1, 3-benzoxazol-3 (2H) -yl) propionate (1R, 2S) -2-amino-3- (3, 5-dichlorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (dipropylamino) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4- [ (6-methylpyridin-2-yl) amino]-4-oxobutanoic acid ester 4- ((1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl) 3-ethyl (4R) -1, 3-oxazolidine-3, 4-dicarboxylate N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-methoxybenzyl) -3-methyl-5- (2-methylbenzoyl) benzamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methylphenyl) butyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-propoxybenzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1-methyl-1H-indole-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-5-chloro-N- (3-ethylbenzyl) -2- (3-methyl-4H-1, 2, 4-triazol-4-yl) benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-difluorophenyl) -N- (3-ethylbenzyl) -2-methoxy-4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [3- (2-thienyl) -1H-pyrazol-1-yl]Acetamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -phenylpentadiamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (2-thioxo-1, 3-benzothiazol-3 (2H) -yl) acetamide N- [ (2R, 3S) -3-amino-4-cyclohexyl-2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-methoxyphenyl) butyl]-N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (3-hydroxy-4-methylphenyl) acetamide N- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -7-fluoro-4H-imidazo [5, 1-c][1，4]Benzoxazine-3-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dihydro-2H-1,5-benzodioxan-7-yl) -N- (3-ethylbenzyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -1-benzofuran-3-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N' - (3, 4-dichlorophenyl) -N- (3-ethylbenzyl) malonamide N¹- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl]-2-hydroxybutyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [ (1R) -2-hydroxy-1-methylethyl]-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methylphenyl) butyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' -pyridin-3-ylglutaramide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-methyl-4-oxo-4H-benzopyran-6-carboxylate 2- ({2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-2-oxoethyl } thio) -N- (5-methylisoxazol-3-yl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- [3- (1H-imidazol-1-yl) propyl]-5-methyl-N ', N' -dipropyl-isophthalamide

N- { (2R, 3S) -3-amino-4- [ 3-fluoro-5- (trifluoromethyl) phenyl ]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (4-hydroxyphenyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide N- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (2-thienyl) butyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- [ (2, 2-dimethylpropanoyl) amino]-N- (3-ethylbenzyl) -2-hydroxybenzamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (4-fluorophenyl) -2-hydroxybutyl]-3- [ (3-methoxybenzyl) amino group]Sulfonyl } -N- [3- (trifluoromethyl) benzyl]Benzamide derivatives N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethyl) phenyl]Butyl } -5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- {6- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ](3-ethylbenzyl) amino]-6-oxohexyl } -2-furoamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (1-phenyl-4, 5-dihydro-1H-tetrazol-5-yl) thio]Acetamide N- [ (2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- { [ (3-methoxybenzyl) amino]Sulfonyl } -N- [3- (trifluoromethyl) benzyl]Benzamide derivatives N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dihydro-2H-chromen-6-yl) -N- (3-ethylbenzyl) -4-oxobutanamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl]-N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methylphenyl) -2-hydroxybutyl]-N- (3-methoxybenzyl) -N ', N' -dipropylglutaramide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) indolizine-2-carboxamide N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) nicotinamide 1-oxide

N- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide 2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-iodobenzyl) amino]-2-oxoethylcarbamate N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2, 3-dihydro-1H-cyclopenta [ b]Quinoline-9-carboxamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3-methyl-1H-pyrazole-5-carboxamide N- {5- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-5-oxopentyl } benzamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- [ (methoxymethyl) thio group]Benzamide derivatives N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (1, 3-benzothiazol-2-yl) -N- (3-ethylbenzyl) -3-methoxypropionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- { [ (methylamino) carbonyl]Amino } -3- (3-thienyl) propanamides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -5-pyridin-2-ylthiophene-2-carboxamide N¹- { (2R, 3S) -3-amino-4- [3- (benzyloxy) -5-fluorophenyl]-2-hydroxybutyl } -N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (5, 6-dimethyl-2, 4-oxo-1, 2, 3, 4-tetrahydropyridin-3-yl) -N- (3-Ethylbenzyl) acetamide N- [ (2R, 3S) -3-amino-4- (3-fluoro-4-methoxyphenyl) -2-hydroxybutyl]-5-methyl-N- (3-methylbutyl) -N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-isobutyl-1, 3-dioxoisoindoline-5-carboxamide 5- (acetylamino) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-furoamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- [ (4-methoxyphenyl) acetyl]Glycine amides N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) isoquinoline-4-carboxamide N¹- { (2R, 3S) -3-amino-4- (3- (benzyloxy) phenyl]-2-hydroxybutyl } -N¹- (3-methylbutyl) -N³，N³-dipropylbenzene-1, 3, 5-triamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (4-hydroxy-3-methoxyphenyl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (4-phenyl-4H-1, 2, 4-triazol-3-yl) thio]Acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (3, 5-dimethoxyphenyl) -N- (3-ethylbenzyl) acetamide N- [ (2R, 3S) -3-amino-2-hydroxy-4- (3-methoxyphenyl) butyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (2-ethyl-4H- [1, 2, 4)]Triazolo [1, 5-a]Benzoimidazol-4-yl) acetamide N- [ (2R, 3S) -3-amino-4- (2-furyl) -2-hydroxybutyl]-N-benzyl-5-methyl-N ', N' -dipropyl-isophthalamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-7-chloro-N- (3-ethylbenzyl) -1-benzofuran-2-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (1, 3-dioxo-1, 3-dihydro-2H-isoindol-2-yl) -N- (3-ethylbenzyl) propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (2-oxo-2H-1, 3-benzoxazine-3 (4H) -yl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (pyrimidin-2-ylthio) acetamide N' - [3- (aminocarbonyl) -4, 5, 6, 7-tetrahydro-1-benzothien-2-yl]-N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (5-phenyl-1, 3, 4-oxadiazol-2-yl) thio]Acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) quinoline-6-carboxamide N¹- [ (2R, 3S) -3-amino-4- (2-furyl) -2-hydroxybutyl]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (2, 3-dihydro-1, 4-benzodioxine-6-yl) -N- (3-ethylbenzyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -3- (1H-indol-3-yl) -1H-pyrazole-5-carboxamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4- { [ (methylamino) thiocarbonyl]Amino-benzamide

N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-6-chloro-N- (3-ethylbenzyl) nicotinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4- (3-hydroxyphenyl) -4-oxobutanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- (phthalazin-1-ylsulfanyl) acetamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- [ (1-oxidopyridin-2-yl) thio]Acetamide 3- (acetylamino) -N- [ (2)R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-fluoro-1H-indole-2-carboxamide N- [ (2S, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- { [ (3-chlorobenzyl) amino]Sulfonyl } -N- [3- (trifluoromethyl) benzyl]Benzamide derivatives N¹- { (2R, 3S) -3-amino-4- [4- (benzyloxy) phenyl]-2-hydroxybutyl } -N¹- (3-methoxybenzyl) -N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N¹- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl ]-N¹-benzyl-N³，N³-dipropylbenzene-1, 3, 5-trimethylamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (3, 4-dichlorophenyl) -N- (3-ethylbenzyl) -2-hydroxy-3-methyl-4-oxobutanamide N- { (2R, 3S) -3-amino-2-hydroxy-4- [3- (trifluoromethoxy) phenyl]Butyl } -3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -N' - (5-methyl-1, 3, 4-thiadiazol-2-yl) succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-2- (2-ethyl-1H-benzimidazol-1-yl) -N- (3-ethylbenzyl) acetamide N- [ (2R, 3S) -3-amino-4- (1, 3-benzodioxol-5-yl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutanBase of]-N- (3-ethylbenzyl) -3- (2-oxo-1, 3-benzoxazol-3 (2H) -yl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-dichlorophenyl) -2-hydroxybutyl]-3- [ (dipropylamino) sulfonyl group]-N- (3-methylbutyl) propanamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N- (3-ethylbenzyl) -N' - (6-methylpyridin-2-yl) succinamide (4R) -4- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -1, 3-oxazolidine-3-carboxylic acid ethyl ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfinyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl S-butyl-N- (methoxycarbonyl) -D-cysteine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (4, 4, 4-trifluorobutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (4, 4, 4-trifluorobutyl) sulfinyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-S- (4, 4, 4-trifluorobutyl) -D-cysteine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (2, 2, 2-trifluoroethoxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (2-cyanoethoxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- { [ (3R) -pyrrolidin-3-yloxy]carbonyl-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- { [ (3S) -tetrahydrofuran-3-yloxy]carbonyl-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [2- (acetylamino) ethoxy]Carbonyl } -3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (pyridin-3-ylmethoxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (pyridin-4-ylmethoxy) carbonyl ]-D-alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- (butylsulfonyl) -N- [ (2-cyanoethoxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (butylsulfonyl) -N (methoxycarbonyl) -D-alanine ester

(1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- [ (2-cyanoethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- { [2- (acetylamino) ethoxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- (methoxycarbonyl) -3- [ (1-propylbutyl) sulfonyl ]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [2- (diethylamino) -2-oxoethoxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (methoxycarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (isopropoxycarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (cyclopropylmethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (allyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- [ (2-cyanoethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [2- (acetylamino) ethoxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (pyridin-3-ylmethoxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (pyridin-4-ylmethoxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl radicalPropyl (2R) -2- { [ (benzyloxy) carbonyl]Amino } -4- (methylsulfonyl) butanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) -L-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -2-hydroxy-1-phenylethyl) ]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1R) -2-methoxy-1-phenylethyl]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [ (1S) -2-methoxy-1-phenylethyl)]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (prop-2-yn-1-yloxy) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl)Radical) amino]Methyl } propyl N- [ (2-methoxyethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [ (3R) -1-acetylpyrrolidin-3-yl ]Oxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3S) -tetrahydrofuran-3-yloxy]carbonyl-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3S) -tetrahydrofuran-3-yloxy]carbonyl-L-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-L-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-1- { [ (cyclopropylmethyl) amino]Methyl } -3- (3, 5-difluorophenyl) propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylphenyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({2- [3- (trifluoromethyl) phenyl)]Ethyl } amino) methyl]Propyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (pyridin-3-ylmethoxy) carbonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl ]-N- { [ (3S) -tetrahydrofuran-3-yloxy]Carbonyl alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N { [ (3R) -tetrahydrofuran-3-yloxy]Carbonyl alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3S) -tetrahydrofuran-3-yloxy]Carbonyl alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [ (3R) -1-acetylpyrrolidin-3-yloxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3R) -pyrrolidin-3-yloxy]Carbonyl alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [ (3R) -1-benzylpyrrolidin-3-yl]Oxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl N- ({ [ (3R) -1, 1-dioxo-tetrahydro-3-thienyl ]Oxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [ (3R) -tetrahydro-3-thienyloxy]Carbonyl alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (cyclopentyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (cyclohexyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (tetrahydro-2H-pyran-4-yloxy) carbonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [1- (methylsulfonyl) piperidin-4-yl)]Oxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [ (1-acetylpiperidin-4-yl) oxy]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group ]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [ (2R) -5-oxopyrrolidin-2-yl]Methoxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- ({ [ (2S) -5-oxopyrrolidin-2-yl]Methoxy } carbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (2-methoxyethoxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (benzyloxy) carbonyl]-3- (butylsulfonyl) alanine ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (benzyloxy) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters N- { (1S, 2R) -1-benzyl-2-hydroxy-3- [ (3-methoxybenzyl) amino]Propyl } -2-hydroxy-4- (phenylsulfonyl) butanamide hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl N²- [ (benzyloxy) carbonyl ]-N⁵，N⁵-dipropyl-L-glutamate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl N²- [ (benzyloxy) carbonyl]-N⁵，N⁵-dipropyl-D-glutamate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (3, 3, 3-trifluoropropionyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (trifluoroacetyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-acetyl-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N-isonicotinoyl-D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (cyclopropylcarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl beta-alanyl-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propylglycyl-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N, N-dimethylglycyl-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N, N-dimethyl-beta-alanyl-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (methoxyacetyl) -D-alanine ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (pyridin-3-ylcarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (2, 4-dimethyl-1, 3-thiazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- { [3- (trifluoromethyl) -1H-pyrazol-4-yl]carbonyl-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (1H-imidazol-4-ylcarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-hydroxy-2- [ (methoxycarbonyl) amino]Pelargonic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (6-hydroxypyridin-3-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- (butylsulfonyl) -N-pyridin-3-ylcarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N-acetyl-3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl N- (cyclopropylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl N-acetyl-3- [ (1-propylbutyl) sulfonyl ]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-isonicotinoyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-bromopyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-chloropyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3,5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-fluorobenzoyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (5-methylpyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-phenylglycyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- { [3- (trifluoromethyl) -1H-pyrazol-4-yl]carbonyl-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (1, 3-thiazol-4-ylcarbonyl) -D-alaninate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (1-acetylpiperidin-4-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [4- (acetylamino) butanoyl group]-3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-acetyl-beta-alanyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (chloroacetyl) -3- [ (1-propylbutyl) sulfonyl ]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (methoxyacetyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-methoxypropionyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2, 2-dimethylpropionyl) -3- [ (1-propylbutyl) sulfonyl group]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino) methyl } propyl N-isobutyryl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-butyryl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-acetyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (1-propylbutyl) sulfonyl ]-N- (pyridin-3-ylcarbonyl) -D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N-isonicotinyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyridin-3-ylcarbonyl) -D-alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (cyclopropylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-propionyl-3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- (butylsulfonyl) -N- (pyridin-3-ylcarbonyl) alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl N-isonicotinyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (6-oxo-1, 4, 5, 6-tetrahydropyridazin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-D-prolyl-3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 5-oxo-L-prolyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [3- (4-oxo-2-thio-1, 3-thiazolidin-3-yl) propanoyl]-3- [ (1-propylbutyl) sulfonyl group ]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (piperidin-4-ylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (2, 4-dimethyl-1, 3-thiazol-5-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [ 2-methyl-4- (trifluoromethyl) -1, 3-thiazol-5-yl]Carbonyl } -3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5)-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (3, 5-dimethylisoxazol-4-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (1H-pyrazol-4-ylcarbonyl) alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- (1H-imidazol-5-ylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (1H-imidazol-4-ylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyrazin-2-ylcarbonyl) alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2, 6-dihydroxyisonicotinoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (6-hydroxypyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R，2S)-2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- [ (6-chloropyridin-3-yl) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-isonicotinoyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyridin-3-ylcarbonyl) alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (pyridin-2-ylcarbonyl) alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (1H-indol-6-ylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine ester hydrochloride (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- (3, 4, 5-trimethoxybenzoyl) alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (2-methylbenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-hydroxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-methylbenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- (3-ethylbenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-chlorobenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [4- (trifluoromethyl) benzoyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (4-methoxybenzoyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [4- (trifluoromethyl) benzoyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (cyclohexylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N-benzoyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group ]-3- (3, 5-difluorophenyl) propyl N-benzoyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (phenylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- (3-phenylpropionyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (benzoylamino) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- (cyclopropylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (methylsulfonyl) acetyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [ (methylthio) acetyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- [4- (methylamino) -4-oxobutanoyl group ]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N- (methylsulfonyl) glycyl-3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl N-acetyl-3- (phenylsulfonyl) alanine esters (1R, 2S) -2-amino-1- { [ (3-methoxy)Benzyl) amino]Methyl } -3-phenylpropyl (2S) -2- [ (4-methoxy-4-oxobutanoyl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- { [ (benzyloxy) carbonyl]Amino } -5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (3-ethoxy-3-oxopropanoyl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl radical N²- (4-methoxy-4-oxobutanoyl) -N⁵，N⁵-dipropyl-D-glutamate

(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (4-methoxy-4-oxobutanoyl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (5-methoxy-5-oxovaleryl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2- (acetoxy) -3- (butylsulfonyl) propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl S-butyl-D-cysteine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfinyl) -D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -L-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- (butylsulfonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-1-alanine esters (1R, 2S) -2-amino-1- [ (cyclopropylamino) methyl group]-3- (3, 5-difluorophenyl) propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-methylbutyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl propyl N- (benzene)Oxoacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl N- { [ (5-chloro-2-thienyl) thio]Peroxy } -3- [ (1-propylbutyl) sulfonyl group]Alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl N- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine esters

(1R, 2S) -3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } -2- (methylamino) propyl N- [ (benzylamino) carbonyl]-3- [ (1-propylbutyl) sulfonyl group]Alanine esters 4- { [ (1R, 2S) -3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } -2- (methylamino) propyl]Oxy } -4-oxo-3- { [ (1-propylbutyl) sulfonyl]Methyl butyric acid 4- [ ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) oxy]-3- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid 1- ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) 4-methyl 2- { [ (3-methylbutyl) sulfonyl]Methyl succinate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4-amino-2- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- (methylamino) -2- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutandinsAcid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- (dimethylamino) -2- { [ (3-methylbutyl) sulfonyl ]Methyl } -4-oxobutanoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate (1R, 2R) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- (ethylsulfonyl) -2- { [ (isobutylsulfonyl) amino]Methyl propionate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3- (ethylsulfanyl) -2- { [ (isobutylsulfonyl) amino]Methyl propionate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2S) -2- { [ (3-methylbutyl) sulfonyl]Amino } -4- (methylsulfonyl) butanoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino ]Methyl } -3-phenylpropyl N- [ (3-methylbutyl) sulfonyl group]-L-methanedisulfonic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 3-(Acetylthio) -2- { [ (3-methylbutyl) sulfonyl]Methyl propionate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (1-propylbutyl) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (3-methylbutyl) sulfonyl group]Propionic acid ester

(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-3- [ (3-methoxyphenyl) sulfonyl group]Propionic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 2-hydroxy-4- (phenylsulfonyl) butanoate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-4- [ (3-methylbutyl) sulfonyl group]Butyric ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- [ (3-methylbutyl) sulfonyl group]-2-phenoxybutyric acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2- (3-methoxyphenoxy) -4- [ (3-methylbutyl) sulfonyl ]Butyric ester 3- {1- { [ ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) oxy]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid 3- {1- { [ ((1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl) Oxy radical]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid methyl ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-4- (phenylsulfonyl) butanoic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-hydroxy-4- (phenylthio) butanoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-methoxy-4- (phenylsulfonyl) butanoic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2-methoxy-4- (phenylthio) butanoic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 4- (phenylsulfonyl) -2-propoxybutyrate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl 2- (benzyloxy) -4- (phenylsulfonyl) butanoic acid esters (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino ]Methyl } -3-phenylpropyl N- [ (benzyloxy) carbonyl]Methanedisulfonic acid ester (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2S) -2-amino-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2S) -2- [ (2-methoxy-2-oxoethyl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2-amino-5-oxo-5-piperidin-1-ylvalerate

(1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (2-ethoxy-2-oxoethyl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (4-ethoxy-4-oxobutyl) amino]-5-oxo-5-piperidin-1-ylvalerate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- [ (methoxycarbonyl) amino]-4-oxooctanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-butyl-N- (methoxycarbonyl) -D-homoserine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxolan-2-yl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxan-2-yl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4, 4-difluoro-2- [ (methoxycarbonyl) amino]Octanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4-fluoro-2- [ (methoxycarbonyl) amino]Octanoic acid ester (1R，2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- [ (methoxycarbonyl) amino]-5-Oxononanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-hydroxy-2- [ (methoxycarbonyl) amino]Pelargonic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxolan-2-yl) -2- [ (methoxycarbonyl) amino]Butyric ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino ]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxan-2-yl) -2- [ (methoxycarbonyl) amino]Butyric ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-fluoro-2- [ (methoxycarbonyl) amino]Pelargonic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5, 5-difluoro-2- [ (methoxycarbonyl) amino]Pelargonic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({1- [3- (trifluoromethyl) phenyl) ]Cyclopropyl } amino) methyl]Propyl 3- (butylsulfonyl) -N- (methoxycarbonyl) -D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({1- [3- (trifluoromethyl) phenyl)]Cyclopropyl } amino) methyl]Propyl 3- (butylsulfonyl) -N- [ (3-methyl-1H-pyrazol-5-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- { [ (methylamino) carbonyl ]Amino } -4-oxooctanoic acid esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 4-butyl-N- [ (methylamino) carbonyl]-D-homoserine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxolan-2-yl) -N- [ (methylamino) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxan-2-yl) -N- [ (methylamino) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4, 4-difluoro-2- { [ (methylamino) carbonyl]Amino octanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4-fluoro-2- { [ (methylamino) carbonyl]Amino octanoate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -2- { [ (methylamino) carbonyl]Amino } -5-oxononanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-hydroxy-2- { [ (methylamino) carbonyl ]Amino-nonanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxolan-2-yl) -2- { [ (methylamino) carbonyl]Amino butyrate (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -4- (2-butyl-1, 3-dioxan-2-yl) -2- { [ (methylamino) carbonyl]Amino butyrate

(1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5-fluoro-2- { [ (methylamino) carbonyl]Amino-nonanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl (2R) -5, 5-difluoro-2- { [ (methylamino) carbonyl]Amino-nonanoic acid ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (methylamino) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- (methylamino) carbonyl-D-alanine ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (methylamino) carbonyl ]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (methylamino) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({1- [3- (trifluoromethyl) phenyl)]Cyclopropyl } amino) methyl]Propyl 3- (butylsulfonyl) -N- (methylamino) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethynylbenzyl) amino]Methyl } propyl 3- (butylsulfonyl) -N- [ (4-methyl-1H-pyrazol-1-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [3- (trifluoromethyl) benzyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (4-methyl-1H-pyrazol-1-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (4-methyl-1H-pyrazol-1-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- ({ [1- (3-ethynylphenyl) cyclopropyl]Amino } methyl) propyl 3- (butylsulfonyl) -N- [ (4-methyl-1H-pyrazol-1-yl) carbonyl]-D-alanine esters (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- [ ({1- [3- (trifluoromethyl) phenyl) ]Cyclopropyl } amino) methyl]Propyl 3- (butylsulfonyl) -N- [ (4-methyl-1H-pyrazol-1-yl) carbonyl]-D-alanine esters [ (1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -3- (methylsulfonyl) propyl]Carbamic acid benzyl ester (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- [ (1-propylbutyl) sulfonyl]-N- [ (tetrahydro-2H-pyran-4-yloxy) carbonyl]Alanine esters S- (3- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl)](3-methoxybenzyl) amino]-2- { [ (3-methylbutyl) sulfonyl]Methyl } -3-oxopropyl) thioacetate N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -2- (3-methoxyphenoxy) -4- [ (3-methylbutyl) sulfonyl]Butylamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl)) -2-hydroxybutyl radical]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -N²- (3, 3, 3-trifluoropropionyl) -D-alaninamide

N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -N²- (trifluoroacetyl) -D-alaninamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl ]-2-methoxy-N- (3-methoxybenzyl) -4- (phenylthio) butanamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N²- (cyclopropylcarbonyl) -N¹- (3-ethylbenzyl) -D-alaninamide beta-alanyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -D-alaninamide glycyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -D-alaninamide (1R, 2S) -2-amino-1- { [ (3-methoxybenzyl) amino]Methyl } -3-phenylpropyl (2R) -2- [ (4-ethoxy-4-oxobutyl) amino]-S-oxo-5-piperidin-1-ylvalerate N, N-dimethyl-beta-alanyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -D-alaninamide N¹-[(2R，3S)-3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -N²- (methoxyacetyl) -D-alaninamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (2-butyl-1, 3-dioxan-2-yl) -N- (methoxycarbonyl) -D-alanine ester N²-acetyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-methylbutyl) -D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹-cyclopropyl-N²- (cyclopropylcarbonyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N²-acetyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N-phenylglycyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N-acetyl-beta-alanyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- (chloroacetyl) -N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluoro)Phenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (methoxyacetyl) -3- [ (1-propylbutyl) sulfonyl group]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N¹- (3-ethylbenzyl) -N²- (3-Methoxypropionyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide

N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- (2, 2-dimethylpropionyl) -N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²-isobutyryl-3- [ (1-propylbutyl) sulfonyl group]-D-alaninamide N²-acetyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- (cyclopropylcarbonyl) -N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²-propionyl-3- [ (1-propylbutyl) sulfonyl]-D-alaninamide 5-oxo-D-prolyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amide hydrochloride 5-oxo-L-prolyl-N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl ]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- [3- (4-oxo-2-thioxo-1, 3-thiazolidin-3-yl) propanoyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (1H-imidazol-4-ylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (Phenylacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (3-phenylpropionyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N- (3- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-3-oxo-2- { [ (1-propylbutyl) sulfonyl]Methyl } propyl) benzamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N²- (Cyclopropylacetyl) -N¹- (3-methoxybenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylButyl radical]-N¹- (3-methoxybenzyl) -N ²- [ (methylsulfonyl) acetyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine amides N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -N²- [ (methylthio) acetyl group]-3- [ (1-propylbutyl) sulfonyl group]Alanine amides N- (methylsulfonyl) glycyl-N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N²-acetyl-N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -3- (phenylsulfonyl) alaninamide

2- [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]-1- [ (butylsulfonyl) methyl group]-2-oxoethyl acetate N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-S-butyl-N¹- (3-ethylbenzyl) -D-cysteine amide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfinyl) -N¹- (3-ethylbenzyl) -D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethylbenzyl) -D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl-3- (butylsulfonyl) -N ¹- (3-ethylbenzyl) -L-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-methylbutyl) -D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- [1- (3-ethylphenyl) cyclopropyl group]-3- [ (1-propylbutyl) sulfonyl group]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-L-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹-cyclopropyl-3- [ (1-propylbutyl) sulfonyl group]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-methylbutyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (Phenoxyacetyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N²- { [ (5-chloro-2-thienyl) thio]Peroxy } -N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N¹- (3-ethylbenzyl) -N²- (phenylsulfonyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides N²- [ (benzylamino) carbonyl]-N¹- [ (2R, 3S) -4- (3, 5-difluorophenyl) -2-hydroxy-3- (methylamino) butyl]-N¹- (3-ethylbenzyl) -3- [ (1-propylbutyl) sulfonyl]Alanine amides 4- [ [ (2R, 3S) -4- (3, 5-difluorophenyl) -2-hydroxy-3- (methylamino) butyl](3-ethylbenzyl) amino]-4-oxo-3- { [ (1-propylbutyl) sulfonyl]Methyl butyric acid

4- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl) amino]-3- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid 4- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl) amino]-3- { [ (3-methylbutyl) sulfonyl]Methyl } -4-oxobutanoic acid methyl ester N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -2- { [ (3-methylbutyl) sulfonyl]Methyl succinamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl-N ¹- (3-methoxybenzyl) -N⁴-methyl-2- { [ (3-methylbutyl) sulfonyl]Methyl succinamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -N⁴，N⁴-dimethyl-2- { [ (3-methylbutyl) sulfonyl]Methyl succinamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -N- (3-ethylbenzyl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionamide (1R, 2S) -2-amino-3- (3, 5-difluorophenyl) -1- { [ (3-ethylbenzyl) amino]Methyl } propyl 3- (4, 4-dimethyl-2, 5-dioxoimidazolidin-1-yl) -2- { [ (1-propylbutyl) sulfonyl]Methyl propionate N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- (ethylsulfonyl) -2- { [ (isobutylsulfonyl) amino]Methyl } -N- (3-methoxybenzyl) propanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-3- (ethylsulfanyl) -2- { [ (isobutylsulfonyl) amino]Methyl } -N- (3-methoxybenzyl) propanamide (2S) -N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -2- { [ (3-methylbutyl) sulfonyl]Amino } -4- (methylsulfonyl) butanamide N¹- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N¹- (3-methoxybenzyl) -N²- [ (3-methylbutyl) sulfonyl group]-L-methanedisulfonamide S- (3- [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutaneBase of](3-methoxybenzyl) amino]-2- { [ (3-methylbutyl) sulfonyl]Methyl } -3-oxopropyl) thioacetate N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (1-propylbutyl) sulfonyl]Propionamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (3-methylbutyl) sulfonyl group]Propionamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -3- [ (3-methoxyphenyl) sulfonyl]Propionamide N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2-hydroxy-4- (phenylsulfonyl) butanamide

N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -4- [ (3-methylbutyl) sulfonyl group]Butylamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl ]-N- (3-methoxybenzyl) -4- [ (3-methylbutyl) sulfonyl]-2-phenoxybutanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -2- (3-methoxyphenoxy) -4- [ (3-methylbutyl) sulfonyl]Butylamide 3- {1- { [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxybenzyl) amino]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid 3- {1- { [ [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl](3-methoxy group)Benzyl) amino]Carbonyl } -3- [ (3-methylbutyl) sulfonyl group]Propoxy benzoic acid methyl ester N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -4- (phenylsulfonyl) butanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-hydroxy-N- (3-methoxybenzyl) -4- (phenylthio) butanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N- (3-methoxybenzyl) -4- (phenylsulfonyl) butanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2-methoxy-N- (3-methoxybenzyl) -4- (phenylthio) butanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -4- (phenylsulfonyl) -2-propoxybutanamide N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-2- (benzyloxy) -N- (3-methoxybenzyl) -4- (phenylsulfonyl) butanamide (2S) -2-amino-N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -5-oxo-5-piperidin-1-ylpentanamide (2R) -2-amino-N- [ (2R, 3S) -3-amino-2-hydroxy-4-phenylbutyl]-N- (3-methoxybenzyl) -5-oxo-5-piperidin-1-ylpentanamide ((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -3-oxoheptyl) carbamic acid methyl ester ((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -3, 3-difluoroheptyl) carbamic acid methyl esterEsters ((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -3-fluoroheptyl) carbamic acid methyl ester ((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -4-oxooctyl) carbamic acid methyl ester

((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -4-hydroxyoctyl) carbamic acid methyl ester [ (1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -3- (2-butyl-1, 3-dioxolan-2-yl) propyl]Carbamic acid methyl ester [ (1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -3- (2-butyl-1, 3-dioxan-2-yl) propyl]Carbamic acid methyl ester ((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -4-fluorooctyl) carbamic acid methyl ester ((1R) -1- { [ [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl](3-ethylbenzyl) amino]Carbonyl } -4, 4-difluorooctyl) carbamic acid methyl ester (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- { [ (methylamino) carbonyl]Amino } -4-oxooctanoic acid amides N¹-[(2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4-butyl-N¹- (3-ethylbenzyl) -N²- [ (methylamino) carbonyl]-D-homoserinamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (2-butyl-1, 3-dioxolan-2-yl) -N¹- (3-ethylbenzyl) -N²- [ (methylamino) carbonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (2-butyl-1, 3-dioxan-2-yl) -N¹- (3-ethylbenzyl) -N²- [ (methylamino) carbonyl]-D-alaninamide (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4, 4-difluoro-2- { [ (methylamino) carbonyl]Amino octanoyl amides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -4-fluoro-2- { [ (methylamino) carbonyl]Amino) octanoyl amides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -2- { [ (methylamino) carbonyl]Amino } -5-oxononanamides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-hydroxy-2- { [ (methylamino) carbonyl]Amino nonanamides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (2-butyl-1, 3-dioxolan-2-yl) -N- (3-ethylbenzyl) -2- { [ (methylamino) carbonyl]Amino-butyramides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-4- (2-butyl-1, 3-dioxan-2-yl) -N- (3-ethylbenzyl) -2- { [ (methylamino) ) Carbonyl radical]Amino-butyramides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5-fluoro-2- { [ (methylamino) carbonyl]Amino nonanamides (2R) -N- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-N- (3-ethylbenzyl) -5, 5-difluoro-2- { [ (methylamino) carbonyl]Amino nonanamides

N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- (3-ethynylbenzyl) -N²- [ (methylamino) carbonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N²- [ (methylamino) carbonyl]-N¹- [3- (trifluoromethyl) benzyl group]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- [1- (3-ethylphenyl) cyclopropyl group]-N²- [ (methylamino) carbonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N¹- [1- (3-ethynylphenyl) cyclopropyl]-N²- [ (methylamino) carbonyl]-D-alaninamide N¹- [ (2R, 3S) -3-amino-4- (3, 5-difluorophenyl) -2-hydroxybutyl]-3- (butylsulfonyl) -N²- [ (methylamino) carbonyl]-N¹- {1- [3- (trifluoromethyl) phenyl ]Cyclopropyl } -D-alaninamide

12. A process for producing a compound of formula (Y):

comprising exposing a compound according to claim 1, wherein R is₁、R₂、R₃、R_NAnd R_CIs as defined in claim 1.

13. The method of claim 12, wherein the production of the compound of formula (Y) occurs in vitro.

14. The method of claim 12, wherein the production of the compound of formula (Y) occurs in vivo.

15. The method of claim 12, wherein the aqueous medium has a pH of about 2 to about 10.

16. The method of claim 3, wherein the aqueous medium has a pH of from about 3 to about 7.

17. A method for the treatment or prevention of alzheimer's disease, mild cognitive impairment, down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the dutch type, cerebral amyloid angiopathy, other degenerative dementias, dementia of mixed vascular and degenerative origin, dementia associated with parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with corticobasal degeneration, diffuse lewy body type alzheimer's disease, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound or salt according to claim 1.

18. A method for the treatment or prevention of alzheimer's disease, mild cognitive impairment, down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the dutch type, cerebral amyloid angiopathy, other degenerative dementias, dementia of mixed vascular and degenerative origin, dementia associated with parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with corticobasal degeneration, diffuse lewy body type alzheimer's disease, which comprises administering to a patient in need thereof a therapeutically effective amount of a compound or salt according to claim 1.

19. Use of a compound or salt according to claim 1 in the manufacture of a medicament.

20. The use of a compound or salt according to claim 1 in the manufacture of a medicament for the treatment or prophylaxis of alzheimer's disease, mild cognitive impairment, down's syndrome, hereditary cerebral hemorrhage with amyloidosis of the dutch-type, cerebral amyloid angiopathy, other degenerative dementias, dementia with mixed vascular and degenerative causes, dementia associated with parkinson's disease, dementia associated with progressive supranuclear palsy, dementia associated with cortical basal degeneration or diffuse lewy body type alzheimer's disease.

21. A compound according to claim 1 selected from the group consisting of:

22. a pharmaceutical composition comprising a compound according to any one of claims 1-11 or 21 in combination with a physiologically acceptable carrier or excipient.