JP2008179621A - Nitrogen-containing saturated heterocyclic compounds - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a nitrogen-containing saturated heterocyclic compound, which is considered to be useful for preventing and treating obesity, hyperlipemia, etc., and exhibits an acetyl-CoA carboxylase inhibitory action. <P>SOLUTION: Provided is a nitrogen-containing saturated heterocyclic compound which is represented by general formula (I) (wherein Y is CH or N; R1 and R4 are the same or different, and an aryl and heteroaryl which may be substituted, a 1-6C alkyl which may be substituted with hydroxy, a 1-6C alkoxy or the like; R2 and R3 are each a hydrogen atom or the like; m and n are each 1 or 2; X is CO or SO<SB>2</SB>; and A is a 1-10C alkyl which may be substituted or the like), its pharmaceutically acceptable salt or its hydrate. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention has an inhibitory action on acetyl-CoA carboxylase (hereinafter sometimes abbreviated as ACC) and has obesity, hyperlipidemia, diabetes, diabetic complications, hypertension, heart failure, diabetic cardiomyopathy, metabolic syndrome And a nitrogen-containing saturated heterocyclic compound useful for prevention / treatment of atherosclerosis and the like.

  ACC is a rate-limiting enzyme that catalyzes fatty acid synthesis by converting acetyl-CoA to malonyl-CoA by an ATP-dependent carbonation reaction. Malonyl-CoA is a precursor in the novel synthesis of fatty acids and the synthesis of long chain fatty acids by carbon chain extension. In addition, malonyl-CoA inhibits fatty acid β-oxidation that occurs in mitochondria by feedback-inhibiting carnitine palmitoyltransferase-1 (CPT-1), an enzyme that transports long-chain fatty acyl CoA into mitochondria. Therefore, malonyl-CoA, an ACC catalytic reaction product, is an important regulator that regulates fatty acid synthesis and fatty acid β-oxidation in response to diet, hormones, or physiological factors (see Non-Patent Documents 1 and 2).

  ACC has two types of isozymes, ACC1 (also known as ACC-α, ACAC, ACACA, and tgf) and ACC2 (also known as ACC-β, ACACB, ACCB, and HACC275). ACC1 is mainly present in tissues involved in lipid synthesis, and is highly expressed, for example, in the liver or adipose tissue. ACC2 is mainly present in tissues involved in β-oxidation of fatty acids, and is highly expressed in, for example, liver or skeletal muscle (see Non-Patent Document 3). Thus, a decrease in malonyl-CoA levels due to ACC1 or ACC2 inhibition may result in suppression of long-chain fatty acid synthesis by the liver and decreased secretion of triglyceride-rich lipoprotein (VLDL), increased fatty acid β oxidation in liver or skeletal muscle, and fatty acid utilization. Can increase. Furthermore, chronic administration of a compound having an ACC1 or ACC2 inhibitory effect can significantly reduce liver and adipose tissue triglyceride content and selectively reduce body fat in obese subjects consuming a low fat diet, It can promote improvement of insulin sensitivity in skeletal muscle and adipose tissue (see Non-Patent Documents 1 and 2).

  Therefore, a compound having an ACC1 or ACC2 inhibitory action is extremely useful for the prevention and treatment of metabolic syndrome, hyperlipidemia, obesity, hypertension, diabetes, cardiovascular disease associated with atherosclerosis, and the like.

Further, as ACC inhibitors, there are disclosures of nitrogen-containing saturated heterocyclic compounds, but none of the patent documents disclose the compounds described in the present application (see Patent Literatures 1 and 2).
Harwood HJ Jr. Expert Opin Ther Targets. 9 (2): 267-81, 2005 Harwood HJ Jr. Curr Opin Investig Drugs. 5 (3): 283-289, 2004 Abu-Elheiga L et al. J Biol Chem. 18; 272 (16): 10669-10677 1997 International Publication No. WO03 / 072197 JP 2006-131559 A

  The object of the present invention is to inhibit ACC and be useful for the treatment and prevention of obesity, hyperlipidemia, diabetes, diabetic complications, hypertension, heart failure, diabetic cardiomyopathy, metabolic syndrome and atherosclerosis etc. Furthermore, it is an object of the present invention to provide a nitrogen-containing saturated heterocyclic compound having characteristics desired as a pharmaceutical such as excellent drug efficacy, specificity, pharmacokinetics, physical properties, and low toxicity.

As a result of intensive studies to achieve the above problems, the present inventors have found that the nitrogen-containing saturated heterocyclic compound represented by the formula (I) has an action of strongly inhibiting ACC. Was completed.
That is, the present invention relates to the formula (I)

[Where
Y represents CH or N;
R1 and R4 are the same or different,
(1) Aryl which may be substituted (Here, the aryl which may be substituted is
A halogen atom,
・ Hydroxy,
-C2-C7 alkoxycarbonyl which may be substituted with a halogen atom, hydroxy, C1-C6 alkoxy, carboxy, dimethylamino, aryl, and -CONR5R6 (wherein R5 and R6 are the same or different, a hydrogen atom, "halogen C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl, or aryl which may be substituted with a halogen atom or hydroxy, or R5 and R6 are Together with the adjacent nitrogen atom, a “nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” may be formed. C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of:
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Formyl cyano,
A C2-C6 alkanoyl optionally substituted with a halogen atom or hydroxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR7R8 (wherein R7 and R8 are the same or different and are a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl", Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R7 and R8 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted with aryl, -CONR9R10 (wherein R9 and R10 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or aryl which may be substituted with hydroxy, or R9 and R10 are adjacent nitrogen atoms and Together, they may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” and C1-. Amino optionally substituted by one or more groups selected from the group consisting of C6 alkylsulfonyl, and C1-C6 alkyl Aryl optionally substituted with one or more groups selected from the group consisting of rusulfonyl. ),
(2) Formula (II)

(In the formula, CycB is a 4- to 8-membered ring structure formed with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and sulfur atom. And the CycB is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom, hydroxy, C1-C6 alkoxy, or amino substituted with C1-C6 alkyl,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR11R12 (wherein R11 and R12 are the same or different and are a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl", Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R11 and R12 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR13R14 (wherein R13 and R14 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl Or a C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or an aryl which may be substituted with hydroxy, or R13 and R14 are an adjacent nitrogen atom and Together, they may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” and C1-. Amino optionally substituted with one or more groups selected from the group consisting of C6 alkylsulfonyl, and C1-C6 A saturated hydrocarbon ring, an unsaturated hydrocarbon ring, a saturated heterocyclic ring or an unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of alkylsulfonyl and arylsulfonyl. A condensed ring represented by

(3) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
-C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy; and-It may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy Heteroaryl which may be substituted with one or more groups selected from the group consisting of C2-C6 alkanoyl. ),
(4) C1-C6 alkyl, or saturated or partially unsaturated heterocycle optionally substituted with oxo (5) C1-C6 alkyl optionally substituted with hydroxy (6) C5-C6 cycloalkenyl or C5- C1-C6 alkyl optionally substituted with C6 cycloalkyl (7) C1-C6 alkoxy (8) oxo and -CONR13R14 (wherein R13 and R14 are the same or different and each represents a hydrogen atom or C1-C6 alkyl). An amino optionally substituted with one or more groups selected from the group consisting of:
R2 and R3 are hydrogen atoms, provided that R1 and R2 may be combined with adjacent carbon atoms to form a benzene ring, and R3 and R4 may be combined with adjacent carbon atoms to form a benzene ring. May be formed,
m and n each represent 1 or 2,
X represents CO or SO ₂ ;

A is
(1) C1-C10 alkyl which may be substituted (Here, C1-C10 alkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkoxy optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and aryl,
A C3-C15 cycloalkyl optionally substituted with one or more groups selected from the group consisting of hydroxy, oxo, C1-C6 alkyl and C1-C6 alkoxy;
C5-C6 cycloalkenyl,
・ Carboxy,
・ Cyano,
・ Oxo,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR15R16 (wherein R15 and R16 are the same or different and are each a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents an aryl optionally substituted with a halogen atom or hydroxy, or R15 and R16 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR17R18 (wherein R17 and R18 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl Or a C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or an aryl which may be substituted with hydroxy, or R17 and R18 are adjacent nitrogen atoms and Together, it may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”), C1-. Selected from the group consisting of C6 alkylsulfonyl, aryl, arylcarbonyl and heteroarylcarbonyl Amino, optionally substituted with one or more groups,

C1-C6 alkylsulfonyl,
An aryl optionally substituted with one or more groups selected from the group consisting of C1-C6 alkoxy optionally substituted with a halogen atom, hydroxy and aryl,
A heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo,
A C8-C10 partially unsaturated hydrocarbon condensed ring, and an aryloxy optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkanoyl,
C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of ),

(2) C2-C10 alkenyl,
(3) C3-C15 cycloalkyl which may be substituted (Here, C3-C15 cycloalkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
C1-C6 alkoxy,
・ Carboxy,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-C3-C15 cycloalkyl which may be substituted with one or more groups selected from the group consisting of arylcarbonyl and aryl which may be substituted with a halogen atom. ),

(4) A saturated or partially unsaturated heterocyclic ring that may be substituted (here, a saturated or partially unsaturated heterocyclic ring that may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
・ Aryl,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of formyl, halogen atoms and oxo,
Hydroxy, C1-C6 alkoxy and “C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted with aryl, —CONR19R20 (wherein R19 and R20 are the same or different, a hydrogen atom , “C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl”, or aryl optionally substituted with a halogen atom or hydroxy, or R19 and R20 together with the adjacent nitrogen atom forms "a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo". And one or more groups selected from the group consisting of C1-C6 alkylsulfonyl. C1-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of “amino optionally substituted”,
C4-C16 cycloalkylcarbonyl,
An arylcarbonyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,

A heteroarylcarbonyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR21R22 (wherein R21 and R22 are the same or different and each is a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R21 and R22 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
A saturated or partially unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl which may be substituted with a halogen atom, and C1-C6 alkylaminosulfonyl. ),

(5) aryl which may be substituted (here, aryl which may be substituted is a halogen atom,
・ Hydroxy,
A C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
A C1-C6 alkoxy which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
・ Carboxy,
・ Cyano,
-C2-C6 alkanoyl optionally substituted with formyl-halogen atom,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of hydroxy, C1-C6 alkoxy and C1-C6 alkanoyloxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR23R24 (wherein R23 and R24 are the same or different and are a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R23 and R24 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".

C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR25R26 (wherein R25 and R26 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl Or a C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or an aryl which may be substituted with hydroxy, or R25 and R26 each represents an adjacent nitrogen atom; Together, they may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” and C1-. An amino optionally substituted with one or more groups selected from the group consisting of C6 alkylsulfonyl,
・ Nitro,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
Arylcarbonyl,
・ Aryloxy,
Heteroaryl,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo, and at least one selected from the group consisting of C1-C6 alkylsulfonyl Aryl optionally substituted with a group is shown. ),

(6) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and saturated heterocycles,
A C1-C6 alkoxy optionally substituted with a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Nitro,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR27R28 (wherein R27 and R28 are the same or different and are each a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R27 and R28 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".

C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR29R30 (wherein R29 and R30 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or aryl which may be substituted with a halogen atom or hydroxy, or R29 and R30 are adjacent nitrogen atoms and Together, it may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”), C1-. C6 alkylsulfonyl, substituted with one or more groups selected from the group consisting of “halogen atom, hydroxy and nitro” An aryl optionally substituted with one or more groups selected from the group consisting of aryl, a saturated heterocyclic ring, and aryloxy optionally substituted with a halogen atom,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups,
-Aryloxy which may be substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups; and-may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl Heteroaryl is shown. ),

(7) a C8-C10 partially unsaturated hydrocarbon condensed ring optionally substituted with one or more groups selected from the group consisting of a halogen atom and oxo;
(8) C1-C6 alkoxy which may be substituted (Here, C1-C6 alkoxy which may be substituted is
-Aryl, or C1-C6 alkoxy which may be substituted with C1-C6 alkoxy which may be substituted with aryl. ),
(9) Aryloxy which may be substituted (Here, aryloxy which may be substituted is
-C1-C6 alkyl which may be substituted with a halogen atom, or aryloxy which may be substituted with C2-C7 alkoxycarbonyl which may be substituted with aryl. ), Or (10) optionally substituted amino (wherein optionally substituted amino is
C1-C6 alkyl which may be substituted with a halogen atom or hydroxy, and amino which may be substituted with one or more groups selected from the group consisting of aryl which may be substituted with halogen atom or hydroxy. )
Indicates. ]
Or a pharmaceutically acceptable salt thereof, or a hydrate thereof.
Another aspect of the present invention is directed to formula (I ′)

[Where
Y ′ represents CH or N;
R1 ′ and R4 ′ are the same or different,
(1) Aryl which may be substituted (Here, the aryl which may be substituted is
A halogen atom,
・ Hydroxy,
A halogen atom, hydroxy, C1-C6 alkoxy, carboxy, C2-C7 alkoxycarbonyl optionally substituted by aryl and -CONR5'R6 '(wherein R5' and R6 'are the same or different, a hydrogen atom, “C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl”, or aryl optionally substituted with halogen atoms or hydroxy, or R 5 ′ and R6 ′ together with the adjacent nitrogen atom forms “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. A C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of:

A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
A C2-C6 alkanoyl optionally substituted with a halogen atom or hydroxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR7'R8 '(wherein R7' and R8 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”, or aryl optionally substituted with a halogen atom or hydroxy, or R7 ′ and R8 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR9'R10 '(wherein R9' and R10 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl "which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl", or aryl which may be substituted with halogen atom or hydroxy, or R9 'and R10' Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. And amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl, and C1-C6 An aryl which may be substituted with one or more groups selected from the group consisting of alkylsulfonyl is shown. ),
(2) Formula (II ′)

(In the formula, CycB ′ is a 4- to 8-membered ring formed together with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and sulfur atom. Shows the structure, and CycB ′ is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted by a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted with a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR11'R12 '(wherein R11' and R12 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R11 ′ and R12 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:

C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, —CONR13′R14 ′ (wherein R13 ′ and R14 ′ are the same or different, a hydrogen atom, “halogen” C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of an atom, hydroxy and aryl, or aryl which may be substituted with a halogen atom or hydroxy, or R13 ′ and R14 ′ Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. And amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl, and C1-C6 A saturated hydrocarbon ring, an unsaturated hydrocarbon ring, a saturated heterocyclic ring or an unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of alkylsulfonyl. A condensed ring represented by
(3) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
-C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy; and-It may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy Heteroaryl which may be substituted with one or more groups selected from the group consisting of C2-C6 alkanoyl. ),

(4) C1-C6 alkyl optionally substituted with hydroxy, or (5) C1-C6 alkoxy,
R2 ′ and R3 ′ are
Hydrogen atoms provided that R1 ′ and R2 ′ may form a benzene ring together with adjacent carbon atoms, and R3 ′ and R4 ′ form a benzene ring together with adjacent carbon atoms. You can,
m ′ and n ′ each represent 1 or 2,
X ′ represents CO or SO ₂ ,
A '
(1) C1-C10 alkyl which may be substituted (Here, C1-C10 alkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkoxy optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and aryl,
A C3-C15 cycloalkyl optionally substituted with one or more groups selected from the group consisting of hydroxy, oxo, C1-C6 alkyl and C1-C6 alkoxy;
C5-C6 cycloalkenyl,
・ Carboxy,
・ Cyano,
・ Oxo,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR15'R16 '(wherein R15' and R16 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R15 ′ and R16 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR17'R18 '(wherein R17' and R18 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of an atom, hydroxy and aryl, or aryl which may be substituted with a halogen atom or hydroxy, or R17 ′ and R18 ′ Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. Selected from the group consisting of C1-C6 alkylsulfonyl, aryl, arylcarbonyl and heteroarylcarbonyl. An amino optionally substituted with one or more groups
C1-C6 alkylsulfonyl,
An aryl optionally substituted with one or more groups selected from the group consisting of C1-C6 alkoxy optionally substituted with a halogen atom, hydroxy and aryl,
A heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo,
A C8-C10 partially unsaturated hydrocarbon condensed ring, and an aryloxy optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkanoyl,
C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of ),

(2) C2-C10 alkenyl,
(3) C3-C15 cycloalkyl which may be substituted (Here, C3-C15 cycloalkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
C1-C6 alkoxy,
・ Carboxy,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-C3-C15 cycloalkyl which may be substituted with one or more groups selected from the group consisting of arylcarbonyl and aryl which may be substituted with a halogen atom. ),

(4) A saturated or partially unsaturated heterocyclic ring that may be substituted (here, a saturated or partially unsaturated heterocyclic ring that may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
・ Aryl,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of formyl, halogen atoms and oxo,
Hydroxy, C1-C6 alkoxy and “C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted with aryl, —CONR19′R20 ′ (wherein R19 ′ and R20 ′ are the same or Differently, a hydrogen atom, “C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl”, or aryl which may be substituted with a halogen atom or hydroxy Or R19 ′ and R20 ′ together with the adjacent nitrogen atom may be substituted with one or more groups selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” One or more groups selected from the group consisting of C1-C6 alkylsulfonyl. C1-C6 alkanoyl which may be substituted with one or more groups selected from the group consisting of “amino optionally substituted with”,
C4-C16 cycloalkylcarbonyl,
An arylcarbonyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
A heteroarylcarbonyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR21'R22 '(wherein R21' and R22 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”, or aryl optionally substituted with a halogen atom or hydroxy, or R21 ′ and R22 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
A saturated or partially unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl which may be substituted with a halogen atom, and C1-C6 alkylaminosulfonyl. ),

(5) aryl which may be substituted (here, aryl which may be substituted is a halogen atom,
・ Hydroxy,
A C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
A C1-C6 alkoxy which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
・ Carboxy,
・ Cyano,
-C2-C6 alkanoyl optionally substituted with formyl-halogen atom,
A C1-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of hydroxy, C1-C6 alkoxy and C1-C6 alkanoyloxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR23'R24 '(wherein R23' and R24 'are the same or different and each may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") -C6 alkyl ", or aryl optionally substituted with a halogen atom or hydroxy, or R23 'and R24' together with the adjacent nitrogen atom are" C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR25'R26 '(wherein R25' and R26 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl "which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl", or aryl which may be substituted with halogen atom or hydroxy, or R25 'and R26' Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. And amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl,

・ Nitro,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
Arylcarbonyl,
・ Aryloxy,
Heteroaryl,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo, and at least one selected from the group consisting of C1-C6 alkylsulfonyl Aryl optionally substituted with a group is shown. ),

(6) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and saturated heterocycles,
A C1-C6 alkoxy optionally substituted with a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Nitro,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR27'R28 '(wherein R27' and R28 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R27 ′ and R28 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:

C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR29'R30 '(wherein R29' and R30 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl ", or aryl which may be substituted with a halogen atom or hydroxy, or R29 'and R30' Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. C1-C6 alkylsulfonyl, one or more groups selected from the group consisting of “halogen atom, hydroxy and nitro”. An optionally substituted aryl, a saturated heterocyclic ring, and an amino optionally substituted with one or more groups selected from the group consisting of an aryloxy optionally substituted with a halogen atom,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups,
-Aryloxy which may be substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups; and-may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl Heteroaryl is shown. ),

(7) a C8-C10 partially unsaturated hydrocarbon condensed ring optionally substituted with one or more groups selected from the group consisting of a halogen atom and oxo;
(8) C1-C6 alkoxy which may be substituted (Here, C1-C6 alkoxy which may be substituted is
-Aryl, or C1-C6 alkoxy which may be substituted with C1-C6 alkoxy which may be substituted with aryl. ),
(9) Aryloxy which may be substituted (Here, aryloxy which may be substituted is
-C1-C6 alkyl which may be substituted with a halogen atom, or aryloxy which may be substituted with C2-C7 alkoxycarbonyl which may be substituted with aryl. ), Or (10) optionally substituted amino (wherein optionally substituted amino is
C1-C6 alkyl which may be substituted with a halogen atom or hydroxy, and amino which may be substituted with one or more groups selected from the group consisting of aryl which may be substituted with halogen atom or hydroxy. )
Indicates. Or a pharmaceutically acceptable salt thereof, or a hydrate thereof.

  The compound of the present invention was confirmed to have an excellent ACC inhibitory action.

  The present invention is described in detail below, but is not particularly limited to those exemplified.

  Aryl means an aryl group such as phenyl or naphthyl.

  The following formula (II) or (II ')

In the condensed ring represented by the formula, CycB or CycB ′ is formed together with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of a carbon atom, an oxygen atom, a nitrogen atom and a sulfur atom. A condensed ring represented by the formula (II) or (II ′) is a 4- to 8-membered ring structure, and includes indanyl, tetrahydronaphthyl, indenyl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzofuryl, Benzothienyl, benzoxazolyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzoxiadiazolyl, benzothiadiazolyl, quinolyl, isoquinolyl, quinoxalyl, quinazolinyl, benzopyranyl, dihydrobenzopyranyl, dihydroquinolyl, Tetrahydroquinolyl, tetrahydroisoquino Le, means benzodioxolyl sulfonyl, benzodioxanyl, benzoxazinyl, indolinyl, isoindolinyl, a fused ring group such as benzimidazolinyl or benzoxazolyl chloride.

  Heteroaryl represented by R1, R1 ′, R4, R4 ′, A and A ′ is pyridyl, pyrimidyl, pyrazolylpyrrolyl, furyl, thienyl, pyrazinyl, pyridazinyl, imidazolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, thiadiazolyl, Means a heteroaryl group such as oxadiazolyl or triazolyl;

  Heteroaryl other than heteroaryl represented by R1, R1 ′, R4, R4 ′, A and A ′ is in addition to heteroaryl, indolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzofuryl, benzothienyl, benz Oxazolyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzoxadiazolyl, benzothiadiazolyl, quinolyl, isoquinolyl, quinoxalyl, quinazolinyl, benzopyranyl, dihydrobenzopyranyl, dihydroquinolyl, tetrahydroquinolyl, Heteroaryls such as tetrahydroisoquinolyl, benzodioxonyl, benzodioxanyl, benzoxazinyl, indolinyl, isoindolinyl, benzimidazolinyl, benzoxazolinyl or carbazolidyl It means Le group.

  C1-C6 alkyl means a straight or branched alkyl group having 1-6 carbon atoms such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl or hexyl.

  C1-C10 alkyl is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-methylbutyl, 2-methylbutyl, 1-ethylpropyl, hexyl, heptyl, It means a linear or branched alkyl group having 1 to 10 carbon atoms such as 1-ethylpentyl, 1-propylbutyl, octyl, 2,5,5-trimethylpentyl, nonyl or decyl.

  C2-C10 alkenyl means a linear or branched alkenyl group having 2 to 10 carbon atoms such as vinyl, allyl, propenyl, butenyl, isobutenyl, pentenyl, hexenyl or 2,6-dimethyl-5-heptenyl. To do.

  C1-C6 alkoxy is linear or branched having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, tert-butoxy, cyclopropylmethoxy, pentyloxy, hexyloxy or cyclohexyloxy -Like alkoxy group.

  C3-C15 cycloalkyl means carbon such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo [2,2,1] heptyl, bicyclo [2,2,2] octyl, adamantyl or cyclododecyl. A cycloalkyl group having a number of 3 to 15 is meant.

  C5-C6 cycloalkyl means cyclopentyl or cyclohexyl.

  C5-C6 cycloalkenyl means cyclopentenyl or cyclohexenyl.

  Saturated heterocycle is azetidinyl, pyrrolidinyl, piperidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, dihydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, dihydrothiopyranyl, tetrahydropyridinyl, dihydropyridinyl , Morpholinyl, thiomorpholinyl, piperazinyl, thiazolidinyl, dioxanyl, imidazolinyl, thiazolinyl, isothiazolidinyl, thiadinanyl, diazepanyl, dioxolanyl and the like.

  Saturated or partially unsaturated heterocycle means azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, tetrahydrofuranyl, tetrahydrofuryl, azetidinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, dihydro Thiopyranyl, tetrahydropyridinyl, dihydropyridinyl, thiomorpholinyl, dioxanyl, imidazolinyl, thiazolinyl, isothiazolidinyl, thiadinanyl, diazepanyl, dioxolanyl, imidazolidinyl, thiazolidinyl, 1,3-oxazodinyl, 1,4,5,6 -Saturated or tetrahydropyridazine, 1,2,3,4-tetrahydropyrimidine, pyrazolidinyl or oxabicyclo [2,2,1] heptyl It means a partially unsaturated heterocyclic group.

  The C8-C10 partially unsaturated hydrocarbon condensed ring means a hydrocarbon condensed ring group having a partially unsaturated bond having 8 to 10 carbon atoms such as benzocyclobutyl, indanyl, indenyl or tetrahydronaphthyl.

  A halogen atom means a fluorine atom, a chlorine atom, a bromine atom, or an iodine atom.

  C1-C6 alkanoyl means a linear or branched alkanoyl group having 1 to 6 carbon atoms such as formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl or hexanoyl.

C2-C6 alkanoyl means a linear or branched alkanoyl group having 2 to 6 carbon atoms such as acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl or hexanoyl.
C1-C6 alkanoyloxy means a group in which an oxygen atom is bonded to the “C1-C6 alkanoyl”, such as acetyloxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy or hexanoyloxy. To do.

  Aryloxy means a group in which the “aryl” and an oxygen atom are bonded, such as phenoxy.

  C2-C7 alkoxycarbonyl means a group in which the “C1-C6 alkoxy” is bonded to carbonyl, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, etc. To do.

    Arylcarbonyl means a group in which the “aryl” and carbonyl are bonded, such as benzoyl.

  The heteroarylcarbonyl means a group in which the “heteroaryl” and the carbonyl are bonded, such as picolinyl, nicotinyl, isonicotinyl, furoyl or isoxazolecarbonyl.

  C4-C16 cycloalkylcarbonyl means a group in which the “C3-C15 cycloalkyl” and carbonyl are bonded, such as cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl or cyclohexylcarbonyl.

  The nitrogen-containing saturated heterocyclic ring means a nitrogen-containing saturated heterocyclic group such as pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl.

  For example, -CONR5R6 is aminocarbonyl, monomethylaminocarbonyl, monoethylaminocarbonyl, monoisopropylaminocarbonyl, dimethylaminocarbonyl, diethylaminocarbonyl, diisopropylaminocarbonyl, diphenylaminocarbonyl, N-phenyl-N-methylaminocarbonyl, 1-pi It means a group such as peridinocarbonyl or 4-morpholinocarbonyl, and -CONR7R8 or -CONR7'R8 'having different numbers in R or R' has the same meaning.

  C1-C6 alkylsulfonyl means a group in which the “C1-C6 alkyl” and sulfonyl are bonded, such as methanesulfonyl or ethanesulfonyl.

  C1-C6 alkylaminosulfonyl is a group in which amino and sulfonyl substituted with one or more of the above “C1-C6 alkyl”, such as monomethylaminosulfonyl, dimethylaminosulfonyl, monoethylaminosulfonyl or diethylaminosulfonyl, are bonded. means.

  The arylsulfonyl means a group in which the above “aryl” and sulfonyl are bonded, such as benzenesulfonyl and p-toluenesulfonyl.

  In the present invention, the pharmaceutically acceptable salt includes salts with mineral acids, organic acids or amino acids, for example, acetic acid, trifluoroacetic acid, maleic acid, tartaric acid, citric acid, succinic acid, fumaric acid, Lactic acid, benzoic acid, malic acid, nicotinic acid, oxalic acid, methanesulfonic acid, ethanesulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, hydroiodic acid And salts with phosphoric acid or sulfuric acid.

  In the present invention, the hydrate is a pharmaceutically acceptable hydrate of the compound of the present invention or a salt thereof. The compound of the present invention and its salt may absorb moisture or become adsorbed water or become a hydrate when exposed to the atmosphere or recrystallized. The compound of the present invention includes such hydrates.

  Some of the compounds of the present invention may exist as optical isomers, stereoisomers, positional isomers, and rotational isomers, and these are also included as the compounds of the present invention and also include mixtures thereof.

The compound of the present invention may be labeled with one or more isotopes. Here, examples of the isotope include ² H, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³⁵ S, ¹⁸ F, ³⁶ Cl, and ¹²⁵ I. In drug development, when testing a compound labeled with a radioisotope, it is preferably a compound labeled with ³ H or ¹⁴ C because of its availability, ease of handling, and detection method.

  The compound of the present invention can be synthesized by a method known per se in the field of chemistry or a method that undergoes one or more processes similar thereto. As such a method, for example, ORGANIC FUNCTIONAL GROUP PREPARATIONS 2nd edition Academic Press, Inc., 1989, Comprehensive Organic Transformation (Comprehensive Organic Transformation) Examples include the methods described in VCH Publishers Inc., 1989, peptide synthesis basics and experiments, published by Maruzen, 1985, and the like.

  In the synthesis of the compounds of the present invention, suitable protection and deprotection methods of functional groups contained in the starting materials or intermediates can be carried out by methods well known to those skilled in the art, for example, protecting groups in organic synthesis (Protecting Groups in Organic). Synthesis) It can be carried out according to the method described in John Willy and Sons (1989).

  Although the general manufacturing method of this invention compound is shown to scheme 1 and 2, the following manufacturing method shows the example of the general manufacturing method of the compound which occupies most of an Example, and does not limit a manufacturing method. It is described in the Examples section that the compounds of the present invention can also be produced using methods other than Schemes 1 and 2.

Scheme 1: A step of converting a compound ( 1 ) to a compound ( 8 ) is shown.

Scheme 1
(Wherein R1, R2, R3, R4, m, n, X, Y, and A are as defined above. P1 and P2 each represent an amino-protecting group. R represents a halogen atom, methane, A leaving group such as a sulfonyloxy group, a p-toluenesulfonyl group, a p-toluenesulfonyloxy group, or a trifluoromethanesulfonyloxy group, and Q represents a halogen atom or a hydroxyl group.
The compound ( 1 ) can be obtained as a commercially available compound, a known compound, or a compound synthesized from an easily available compound using various organic synthesis methods known to those skilled in the art.

Production method of compound ( 3 ): Compound ( 3 ) can be obtained by performing “amidation reaction” using compound ( 1 ) and compound ( 2 ), followed by “deprotection reaction” of protecting group P1.

Examples of the “amidation reaction” include (i) in the presence of an appropriate base such as triethylamine or N, N-diisopropylethylamine in an inert solvent such as dichloromethane or chloroform at a temperature of 0-60 ° C. N, N′-dicyclohexylcarbodiimide (DCC), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC · HCl), benzotriazo-1-yloxytris (dimethylamino) phosphonium hexafluorophosphate ( BOP), 3- (diethoxyphosphoryloxy) -1,2,3-benzotriazin-4 (3H) -one (DEPET), O-benzotriazol-1-yl-N, N, N ′, N′— Tetramethylronium hexafluorophosphate (HBTU), diphenylphospho Amidation reaction using a condensing agent such as ruazide or carbonylimidazole, and (ii) a suitable base such as triethylamine or N, N-diisopropylethylamine in an inert solvent such as dichloromethane or chloroform at a temperature of 0 ° C to 60 ° C. Amidation reaction via mixed acid anhydride using ethyl chlorocarbonate, isobutyl chlorocarbonate or pivaloyl chloride in the presence or absence, (iii) compound ( 1 ) with an inert solvent such as benzene or toluene In the presence or absence of N, N-dimethylformamide, after reacting with thionyl chloride, oxalyl chloride, phosphorus trichloride, phosphorus pentachloride or the like to obtain the corresponding acid chloride, at a temperature of 0-60 ° C , Triethylamine or N, N-diisopropyl chloride in an inert solvent such as dichloromethane or chloroform Suitable bases presence or absence of ethylamine, amidation reaction is reacted with the compound (2).

  When performing an amidation reaction using a condensing agent, additives such as 1-hydroxysuccinimide (HOSu) or 1-hydroxybenzotriazole (HOBt) can be used as necessary. In the amidation reaction using a condensing agent, a method using EDC · HCl in the presence of HOBt in a chloroform solvent at room temperature is preferable.

In the amidation reaction using an acid chloride, the acid chloride obtained by using oxalyl chloride and the compound ( 2 ) in a toluene solvent in the presence of a catalytic amount of N, N-dimethylformamide are added at room temperature in a chloroform solvent. Conditions for the reaction in the presence of triethylamine are preferred.

  Examples of the “deprotection reaction” include (i) when the protecting group P1 is a benzyl group, a benzyloxycarbonyl group or a benzhydryl (diphenylmethyl) group, the presence of an acid in an inert solvent at a temperature of 0-80 ° C. In the presence or absence, palladium-activated carbon or rhodium-activated carbon can be removed by a hydrogenolysis reaction using a catalytic amount. (Ii) Especially when the protective group P1 is a benzyloxycarbonyl group A method of removing hydrogen bromide by reacting in acetic acid at a temperature of 0-60 ° C., (iii) when the protecting group P1 is a tert-butoxycarbonyl group, at a temperature of 0-60 ° C., dichloromethane, chloroform, In an inert solvent such as methanol, ethyl acetate or 1,4-dioxane or without solvent, trifluoroacetic acid, 4M hydrochloric acid-ethyl acetate or 4M hydrochloric acid-dio A method of removing by reacting the acid.

In particular, when a compound that is an amine having no protecting group P1 is used in the compound ( 2 ), the compound ( 3 ) can be obtained directly by using the above-mentioned "amidation reaction".

Production method of compound ( 6 ): by performing “reductive amination reaction” using compound ( 3 ) and compound ( 4 ), or “alkylation reaction” using compound ( 3 ) and compound ( 5 ) A compound ( 6 ) can be obtained.

As the “reductive amination reaction”, for example, at a temperature of 0-50 ° C., in a reaction inert solvent such as tetrahydrofuran, chloroform, dichloromethane, methanol, ethanol or N, N-dimethylformamide, in the presence or absence of an acid And reaction using a reducing agent such as sodium borohydride, sodium cyanoborohydride or sodium triacetoxyborohydride.
In the reductive amination reaction using sodium cyanoborohydride, titanium tetraisopropoxide can also be added.
In the reductive amination reaction, a method using sodium triacetoxyborohydride in a chloroform solvent is preferable.

As the “alkylation reaction”, for example, a compound ( 3 ) and a compound ( 5 ) having a leaving group R are reacted with a compound such as N, N-dimethylformamide or N-methylpyrrolidinone at a temperature of 25 to 140 ° C. The method of making it react in an active solvent is mentioned.

Production method of compound ( 7 ): Compound ( 7 ) can be obtained by carrying out “deprotection reaction” of protecting group P2 of compound ( 6 ). Here, the “deprotection reaction” includes the same reaction as the “deprotection reaction” for obtaining the above-mentioned compound ( 3 ).

Production method of compound ( 8 ): Compound ( 8 ) can be obtained by performing "amidation reaction" using compound ( 7 ) and a compound represented by QX-A. The compound represented by QX-A is a compound synthesized from a commercially available compound or a known compound. Here, the “amidation reaction” includes the same reaction as the above-mentioned “amidation reaction”.

Scheme 2: A step of converting the compound ( 2 ) to the compound ( 13 ) is shown.

Scheme 2
(In the formula, R1, R2, R3, R4, m, n, X, Y, and A are as defined above. P represents a protecting group for an amino group. R represents a halogen atom or methanesulfonyloxy. A leaving group such as a group, p-toluenesulfonyloxy group, trifluoromethanesulfonyloxy group, etc.)
Production method of compound ( 11 ): by performing “reductive amination reaction” using compound ( 2 ) and compound ( 9 ), or “alkylation reaction” using compound ( 2 ) and compound ( 10 ) A compound ( 11 ) can be obtained. Here, the “reductive amination reaction” includes the same reaction as the above-mentioned “reductive amination reaction”, and the “alkylation reaction” includes the same reaction as the above-mentioned “alkylation reaction”. It is done.

Production method of compound ( 12 ): Compound ( 12 ) can be obtained by performing “deprotection reaction” using compound ( 11 ). Here, the “deprotection reaction” includes the same reaction as the aforementioned “deprotection reaction”.

Production method of compound ( 13 ): Compound ( 13 ) can be obtained by carrying out an “amidation reaction” using compound ( 12 ). Here, as the “amidation reaction”, the same reaction as the above-mentioned “amidation reaction” is used.

An aryl boron compound in the presence of a palladium catalyst using each of the compounds ( 1 ), ( 3 ), ( 6 ), ( 7 ), ( 8 ) or ( 13 ), wherein the substituents R1 and R4 are single or both are halogen atoms The corresponding coupling compound can be obtained by conducting a coupling reaction with a vinylboron compound, an aryltin compound, a heteroaryltin compound or a vinyltin compound.

The coupling reaction is, for example, at a temperature of 60 to 160 ° C. in an inert solvent such as 1,2-dimethoxyethane, acetonitrile, toluene, tetrahydrofuran, dimethyl sulfoxide, or 1,4-dioxane, in the presence of a palladium catalyst and a base. And a method of reacting each compound ( 1 ), ( 3 ), ( 6 ), ( 7 ), ( 8 ) or ( 13 ) with an arylboron compound or vinylboron compound. The reaction can also use a microwave.

  Examples of the palladium catalyst used for the coupling reaction include tetrakistriphenylphosphine palladium (0), bis (dibenzylideneacetone) palladium (0), bis (triphenylphosphine) palladium (II) dichloride, bis (triphenylphosphine) palladium ( II) Palladium catalysts known to those skilled in the art such as acetate or [1,1′-bis (diphenylphosphino) ferrocene] palladium (II) dichloride dichloromethane complex (1: 1). Further, a palladium (0) catalyst can be generated in the system using palladium (II) acetate or palladium-activated carbon and triphenylphosphine in the presence of a base and used for the reaction.

  As the base used for the coupling reaction, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, tripotassium phosphate and the like are preferable.

  The arylboron compound used in the coupling reaction is a compound in which the above-mentioned “optionally substituted aryl” and boron are bonded, and examples thereof include phenylboronic acid, and the vinylboron compound includes the above-mentioned “ This is a compound in which carbon and boron are bonded to the double bond of “C2-C10 alkenyl that may be substituted”, and examples thereof include vinyl boronic acid. As the aryl tin compound, the above-mentioned “aryl that may be substituted” A compound in which tin is bonded, for example, tributylphenyltin, and the heteroaryltin compound is a compound in which tin described above is bonded to “heteroaryl”, for example, tributyl (2-pyridyl) tin. As the vinyl tin compound, “optionally substituted C2-C6 alkenyl” A compound double bond on the carbon and tin is bonded, for example, tributyl vinyl tin.

  The room temperature in the description of the general production method of the compound of the present invention means 0-40 ° C., and the reaction time is 0.1-24 hours.

  The base, acid, and inert solvent in the description of the general production method of the compound of the present invention will be described more specifically, but are not limited to the following examples. Also, the isolation techniques that can be used are specifically described.

  “Base” means, for example, an alkali metal or alkaline earth metal hydride (lithium hydride, sodium hydride, potassium hydride, calcium hydride, etc.), an alkali metal or alkaline earth metal amide (lithium amide). , Sodium amide, lithium diisopropylamide, lithium dicyclohexylamide, lithium hexamethyldisilazide, potassium hexamethyldisilazide, etc.), alkali metal or alkaline earth metal C1-6 alkoxide (sodium methoxide, sodium ethoxide, potassium) tert-butoxide), alkali metal or alkaline earth metal hydroxides (sodium hydroxide, potassium hydroxide, lithium hydroxide, barium hydroxide, etc.), alkali metal or alkaline earth metal carbonates (sodium carbonate, Carbonic acid Lithium, cesium carbonate, etc.), alkali metal bicarbonates (sodium bicarbonate, potassium bicarbonate, etc.), inorganic bases such as phosphates with alkali metals or alkaline earth metals (tripotassium phosphate, etc.), amines (Triethylamine, diisopropylethylamine, N-methylmorpholine, etc.), basic heterocyclic compounds (pyridine, 4-dimethylaminopyridine, DBU (1,8-diazabicyclo [5.4.0] undes-7-ene), DBN ( 1,5-diazabicyclo [4.3.0] non-5-ene), imidazole, 2,6-lutidine and the like.

  Examples of the “acid” include inorganic acids (hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.) and organic acids (p-toluenesulfonic acid, methanesulfonic acid, trifluoroacetic acid, formic acid, acetic acid, etc.). Can be mentioned.

Examples of the “inert solvent” include nitrile solvents, amide solvents, carbon halide solvents, ether solvents, aromatic solvents, hydrocarbon solvents, ester solvents, alcohol solvents, sulfoxide solvents, Water may be mentioned, and these may be used as a mixture of two or more at an appropriate ratio.
As the nitrile solvent, for example, acetonitrile or propionitrile is used. Examples of the amide solvent include N, N-dimethylformamide, N, N-dimethylacetamide, and N-methylpyrrolidone. Examples of the halogenated carbon solvent include dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride. Examples of the ether solvent include diethyl ether, tetrahydrofuran, 1,4-dioxane, and 1,2-dimethoxyethane. Examples of the aromatic solvent include benzene, toluene, xylene, and pyridine. Examples of the hydrocarbon solvent include hexane, pentane, and cyclohexane. Examples of the ester solvent include ethyl acetate and ethyl formate. Examples of the alcohol solvent include methanol, ethanol, isopropyl alcohol, tert-butyl alcohol, and ethylene glycol. Examples of the sulfoxide solvent include dimethyl sulfoxide.

  The compound (I) or (I ′) obtained by the above production method can be isolated and purified by known means such as solvent extraction, liquid conversion, phase transfer, crystallization, recrystallization, and chromatography. .

  Protecting groups that can be used by the compounds in the general production of the compounds of the present invention are described below, but are not limited to the examples, and can be appropriately selected.

  Examples of amino-protecting groups include C1-C6 acyl groups (formyl, acetyl, propionyl, etc.) generally used during peptide synthesis, C2-C12 alkoxycarbonyl groups (methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, Benzyloxycarbonyl, 9-fluorenylmethylenoxycarbonyl, etc.), arylcarbonyl groups (benzoyl, etc.), trityl groups, phthaloyl groups, N, N-dimethylaminomethylene groups, substituted silyl groups (trimethylsilyl, triethylsilyl, dimethylphenyl) Silyl, tert-butyldimethylsilyl, tert-butyldiethylsilyl, etc.) and C2-C6 alkenyl groups (1-allyl etc.). These groups may be substituted with one or more substituents selected from a halogen atom, a C1-C6 alkoxy group (methoxy, ethoxy, propoxy, etc.) and a nitro group.

  Examples of the protecting group for the carboxy group include a C1-C6 alkyl group (methyl, ethyl, tert-butyl, etc.), a C7-C20 aralkyl group (benzyl, trityl, etc.), a phenyl group, a substituted silyl group (trimethylsilyl, triethylsilyl, Dimethylphenylsilyl, tert-butyldimethylsilyl, tert-butyldiethylsilyl, etc.) and C2-C6 alkenyl groups (1-allyl etc.). These groups may be substituted with one or more substituents selected from a halogen atom, a C1-C6 alkoxy group (methoxy, ethoxy, propoxy, etc.) and a nitro group.

  Examples of the protective group for the hydroxy group include C1-C6 alkyl groups (methyl, ethyl, tert-butyl, etc.), C7-C20 aralkyl groups (benzyl, trityl, etc.), phenyl groups, substituted silyl groups (trimethylsilyl, triethylsilyl, Dimethylphenylsilyl, tert-butyldimethylsilyl, tert-butyldiethylsilyl, etc.), C2-C6 alkenyl group (1-allyl etc.), C1-C6 acyl group (formyl, acetyl, propionyl etc.), C2-C12 alkoxycarbonyl group (Methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, benzyloxycarbonyl, 9-fluorenylmethylenoxycarbonyl, etc.), arylcarbonyl group (benzoyl, etc.), 2-tetrahydropyranyl group, 2-tetrahydrofuranyl And the like. These groups may be substituted with one or more substituents selected from a halogen atom, a C1-C6 alkoxy group (methoxy, ethoxy, propoxy, etc.), and a nitro group.

  Examples of the protecting group for the carbonyl group include cyclic acetals (1,3-dioxane, 1,3-dioxolane, etc.) and acyclic acetals (di-C1-C6 alkyl acetals (dimethyl acetal, diethyl acetal, etc.)). .

  In order to use the compound of the present invention as a pharmaceutical, any form of a solid composition, a liquid composition and other compositions may be used, and an optimum one can be selected as necessary. The medicament of the present invention can be produced by blending a pharmaceutically acceptable excipient with the compound of the present invention. Specifically, conventional excipients, binders, coating agents, adhesives, dragees, emulsifiers, dispersants, disintegrants, pH adjusters, solvents or solubilizers are added, and conventional formulation techniques are used. , Tablets, troches, pills, capsules, powders, granules, ointments, suspensions, emulsifiers, solutions, syrups, suppositories, inhalants or injections.

  The dose of the compound of the present invention varies depending on the administration subject, administration route, target disease, symptom, and the like. For example, when administered orally to an adult diabetic patient, the dose is usually about 0.01 to 1000 mg / kg body weight. , Preferably 0. 05-300 mg / kg body weight, more preferably 0. It is 1-100 mg / kg body weight, and it is desirable to administer this amount once or several times a day.

  The compound of the present invention contains obesity, hyperlipidemia (eg, hypertriglyceridemia, hypercholesterolemia, hypoHDLemia, postprandial hyperlipidemia, etc.), diabetes (eg, type 1 diabetes, type 2 diabetes, It can be used as a prophylactic or therapeutic agent for gestational diabetes, etc., diabetic complications, hypertension, heart failure, diabetic cardiomyopathy, metabolic syndrome or atherosclerosis.

  For example, in the prevention or treatment of diabetes or metabolic syndrome, the compound of the present invention is used for the purpose of enhancing the action of the compound or reducing the dose of the compound, etc. It can be used in combination with drugs such as symptomatic drugs, antihypertensive drugs, antiobesity drugs, diuretics and antithrombotic drugs (hereinafter abbreviated as concomitant drugs). In this case, the administration time of the compound of the present invention and the concomitant drug is not limited, and these may be administered to the administration subject at the same time or may be administered with a time difference. Furthermore, the compound of the present invention and the concomitant drug may be administered as two types of preparations containing each active ingredient, or may be administered as a single preparation containing both active ingredients. The dose of the concomitant drug can be appropriately selected based on the clinically used dose. The compounding ratio of the compound of the present invention and the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptom, combination and the like. For example, when the administration subject is a human, the concomitant drug may be used in an amount of 0.01 to 100 parts by weight per 1 part by weight of the compound of the present invention.

  Examples of diabetes therapeutic agents include insulin preparations (eg, animal insulin preparations extracted from bovine and porcine pancreas; human insulin preparations synthesized by genetic engineering using Escherichia coli or yeast; insulin zinc; protamine insulin zinc; Insulin fragment or derivative (eg, INS-1 etc.), oral insulin preparation), insulin resistance improving agent (eg, pioglitazone or a salt thereof (preferably hydrochloride), rosiglitazone or a salt thereof (preferably maleate) Riboglitazone (CS-011) (R-119702), Sipoglitazar (TAK-654), Metaglidasen (MBX-1 0 2), Naveglitazar (Naveglitazar) LY-5 1 9 8 1 8), MX-6054, Balaglitazone (NN-2344), T-13 (AMG 131)), PPA Rγ agonist, PPA Rγ antagonist, PPA Rγ / α dual agonist, α-glucosidase inhibitors (eg, voglibose, acarbose, miglitol, emiglitate), biguanides (eg, phenformin, metformin, buformin or their salts (eg, hydrochloride, fumarate, succinate)), insulin secretion Accelerator (eg sulfonylurea (eg, tolbutamide, glibenclamide, gliclazide, chlorpropamide, tolazamide, acetohexamide, glyclopyramide, glimepiride, glipizide, glybazole, etc.), repaglinide, senaglinide, nateglinide, mitiglinide or its calcium Um salt hydrate], GPR40 agonist, GPR40 antagonist, GLP-1 receptor agonist [eg, GLP-1, GLP-1 MR agent, Liraglutide (NN-2211), Exenatide (AC-2993) (exendin-4 ), Exenatide LAR, BIM51077, A ib (8, 35) hGLP-1 (7, 37) NH2, CJC-1 13 1, AVE0010, GSK-716155], amylin agonist (eg, pramlintide), phosphotyrosine phosphatase Inhibitors (eg, sodium vanadate), dipeptidyl peptidase I V inhibitors (eg, compounds described in WO02 / 038541, NVP-DPP-278, PT-100, P32 / 98, vildagliptin ( AF-237), P93 / 01, sitagliptin (MK-431), saxagliptin (BMS-477118), SYR-322, MP-513, T-6666, GRC-8200, etc.), β3 agonist ( Examples, AJ-9679, AZ40140, etc.), gluconeogenesis inhibitors (eg, glycogen phosphorylase inhibitors, glucose-6-phosphatase inhibitors, glucagon antagonists, fructose-1,6-bisphosphatase inhibitors), SGLT (sodium- glucose transporter) inhibitors (eg, compounds described in WO04 / 014931, WO04 / 089967, WO06 / 073197, T-1095, Serglflozin (GSK-869682), GSK-1 9075, KGT-1251, KGT-1681, KGA-2727, BMS-512148, AVE2268, SAR7226, etc.), 11β-hydroxysteroid dehydrogenase inhibitor (eg, compounds described in WO06051662, BVT-3498, INCB13739), GPR119 agonist (Eg, PSN-632408, APD-668), adiponectin or agonist thereof, IKK inhibitor (eg, AS-2868), AMPK activator, leptin resistance ameliorating agent, somatostatin receptor agonist, glucokinase activation Examples include drugs (eg, Ro-28-1675), pancreatic lipase inhibitors (eg, orlistat, ATL-962), and DGAT-1 inhibitors.

  Examples of the therapeutic agent for diabetic complications include aldose reductase inhibitors (eg, tolrestat, epalrestat, zenarestat, zopolrestat, minalrestat, fidarestat, CT-112), neurotrophic factors and their increasing agents (eg, NGF). , NT-3, BDNF, neurotrophin production / secretion promoter), nerve regeneration promoter (eg, Y-128), PKC inhibitor (eg, ruboxistaurine mesylate (LY-333531)) AGE inhibitors (eg, ALT946, pimagedin, pyratoxatin, N-phenacylthiazolium bromide (ALT766), ALT-711, EXO-2 26, pyridoline, pyridoxamine), active oxygen scavengers (eg, Thioctic acid), brain Tube expansion agent (e.g., tiapride, mexiletine), somatostatin receptor agonists (e.g., B I M 2 3 1 9 0), apoptosis signal regulating kinase--1 (ASK-1) inhibitors.

  Antihyperlipidemic agents include, for example, statin compounds (eg, pravastatin, simvastatin, lovastatin, atorvastatin, fluvastatin, itavastatin, rosuvastatin, pitavastatin or their salts (eg, sodium salt, calcium salt)), squalene synthesis Enzyme inhibitors (eg, TAK-475), fibrate compounds (eg, bezafibrate, clofibrate, simfibrate, clinofibrate), ACAT inhibitors (eg, avasimibe, elucimibe), anion exchange resin (Eg, cholestyramine), probucol, nicotinic acid drugs (eg, nicomol, nicoritrol), ethyl icosapentate, plant sterols (eg, soto) Isterol, γ-oryzanol, CETP inhibitors (eg, Torcetrapib, JTT-705, JTT-302, FM-VP4, etc.), cholesterol absorption inhibitors (eg, ezetimibe, etc.) Is raised.

  Examples of the antihypertensive agent include angiotensin converting enzyme inhibitors (eg, captopril, enalapril, delapril), angiotensin II antagonists (eg, candesartan cilexetil, losartan, eprosartan, valsartan, telmisartan, irbesartan, tasosartan, azilsartan (TAK-536) ), Calcium antagonists (eg, manidipine, nifedipine, amlodipine, efonidipine, nicardipine), potassium channel openers (eg, lebucromacarim, L-2 7 1 5 2, A L0 6 7 1, NIP-12 1), clonidine Is mentioned.

  Examples of anti-obesity agents include central anti-obesity agents (eg, dexfenfluramine, fenfluramine, phentermine, sibutramine, amphetopramone, dexamphetamine, mazindol, phenylpropanolamine, clobenzorex; MCH receptor antagonist (Eg, compounds described in WO06 / 035967, SB-5 6 8 8 4 9; SNAP-7 9 4 1, T-226296); neuropeptide Y antagonists (eg, CP-4 2 2 9 3 5); Cannabinoid receptor antagonists (eg, rimonabant (SR-1 4 1 7 1 6), SR-147778); ghrelin antagonists; 1 1β-hydroxysteroid dehydrogenase inhibitors (eg, BVT-3 4 98, INCB13739)), pancreatic lipase inhibitor (eg, orlistat, ATL-962), DGAT-1 inhibitor, β3 agonist (eg, A -9 6 7 7, AZ4 0 1 4 0), peptidic appetite suppressant (eg, leptin, CNTF (ciliary neurotrophic factor)), cholecystokinin agonist (eg, Lynchtripto, FPL-15849), feeding Inhibitors (eg, P-57) can be mentioned.

  Examples of diuretics include xanthine derivatives (eg, sodium salicylate theobromine, calcium salicylate theobromine), thiazide preparations (eg, etiazide, cyclopentiazide, trichloromethiazide, hydrochlorothiazide, hydroflumethiazide, benchylhydrochlorothiazide, pentfurizide, polythiazide. , Methiclotiazide), anti-aldosterone preparations (eg, spironolactone, triamterene), carbonic anhydrase inhibitors (eg, acetazolamide), chlorobenzenesulfonamide preparations (eg, chlorthalidone, mefluside, indapamide), azosemide, isosorbide, ethacrynic acid, Piretanide, bumetanide, furosemide.

  Examples of the antithrombotic agent include heparin (eg, heparin sodium, heparin calcium, dalteparin sodium, AVE-5026), warfarin (eg, warfarin potassium, etc.), antithrombin drug (eg, argatroban) , Ximelagatran, Dabigatran, Odiparcil, Lepirudin, bivalirudin, Desirudin, ART-123, Idraparinux, SR-12571, TCG-9737, TCG-9737, TCG-9737, TCG-9737 -30870, MPC-0920, Pegmusirudin, Org-426951, etc.), thrombolytic drugs ( Urokinase, tisokinase, alteplase, natepase, monteplase, pamiteplase, etc., platelet aggregation inhibitor (e.g., ticlopidine hydrochloride) ), Ethyl icosapentate, beraprost sodium, sarpogrelate hydrochloride, etc.), anti-Xa inhibitors (eg, Fondaparinux, BAY-59-7939, DU-176b, YM-150, SR-1x, SRp 1257, SRp. , Razababan, LY-517717 MLN-102, Octaparine, Otamixaban, EMD-503982, TC-10, CS-3030, AVE-3247, GSK-838893, KFA-1982, etc., plasma carboxypeptidase B (or active thrombin-activable fibrinobinitis) Inhibitors (also known as TAFIa]) (eg, AZD-9684, EF-6265, MN-462) and the like.

  The present invention will be described in more detail with reference to the following Reference Examples, Examples, Experimental Examples and Formulation Examples, which are not intended to limit the present invention, and may be changed without departing from the scope of the present invention. May be.

NMR (nuclear magnetic resonance) spectra were measured at room temperature at 200 MHz (GEMINI 2000/200, Varian Instruments) 300 MHz (INOVA 300, Varian Instruments) 600 MHz (JEOL JNM-ECA600, JEOL). Deuterium such as deuterated chloroform (CDCl ₃ ), deuterated dimethyl sulfoxide (DMSO-d ₆ ), deuterated methanol (MeOH-d ₄ ), deuterated acetonitrile (acetonitrile-d ₃ ), deuterated water (D ₂ O) Solvent was used. The chemical shift value in this specification is indicated by the parts per million (δ) value relative to the internal standard substance (tetramethylsilane).

  It is well known to those skilled in the art that compounds having amide rotamers such as compound (I) or (I ') usually give complex NMR spectra. Therefore, analysis of the NMR spectrum given by the compound of this example may be difficult. Although it may be incomplete in nature, in this example, normal NMR measurement was performed, and only the spectrum of the compound that gave a readable signal among the obtained NMR spectra was measured. Describe the shape and chemical shift value.

  The mass spectrum was measured by micromass Platform-LC mass spectrometer (EI: electron ionization method) or Shimadzu LCMS-2010EV (ESI: electrospray ionization method / APCI: atmospheric pressure ionization method Dual).

  The degree of progress of the reaction was measured using TLC (Silica gel 60, F254; manufactured by Merck).

For silica gel column chromatography, Kanto Chemical “silica gel 60” or “silica gel 60N” and Fuji Silysia Chemical “chromatorex NH” were used. Unless otherwise noted, Kanto Chemical “silica gel 60N” was used.
When the product was purified by preparative TLC, Merck silica gel 60, 1 mm, F254 was used.

In the present Reference Examples and Examples, the reaction using the microwave was Initiator Sixty ^™ manufactured by Biotage.

Reference Example 1 tert-butyl-4- (2,6-diphenylisonicotinoyl) piperazine-1-carboxylate
Thionyl chloride (41 ml, 551 mmol) was added to a suspension of 2,6-diphenylisonicotinic acid (25.25 g, 92 mmol) in chloroform (containing amylene) (100 ml), and the mixture was stirred for 3 hours while heating under reflux. The solvent was distilled off under reduced pressure to obtain 2,6-diphenylisonicotinic acid chloride. A suspension of the resulting 2,6-diphenylisonicotinic acid chloride in chloroform (containing amylene) (100 ml) was mixed with 1- (tert-butoxycarbonyl) piperazine (17.1 g, 92 mmol) and triethylamine (13 ml, 92 mmol) in chloroform. The solution was added to (amylene-containing) solution (100 ml) under ice-cooling and stirred at room temperature for 1 hour. The reaction solution was washed with water, saturated aqueous sodium hydrogen carbonate solution, saturated aqueous ammonium chloride solution and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (ethyl acetate / hexane) to obtain the title compound (38.84 g, 87 mmol, 95%) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.47 (s, 9 H), 3.38-3.49 (m, 4 H), 3.53-3.63 (m, 2 H), 3.76-3.87 (m, 2 H), 7.42-7.56 (m, 6 H), 7.66 (s, 2 H), 8.11-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 444.3 [M + H] ⁺ .
Reference Example 2 1- (2,6-Diphenylisonicotinoyl) piperazine
To a solution of tert-butyl-4- (2,6-diphenyl) piperazine-1-carboxylate (38.84g, 87mmol) in methanol (200ml) was added 4M hydrochloric acid-ethyl acetate solution (100ml) and stirred at room temperature for 13 hours. did. Under ice-cooling, 3M aqueous sodium hydroxide solution was added to the reaction system to make it alkaline, and the mixture was extracted with chloroform. The obtained organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, a crude product (28.79 g, 96%) containing the title compound was obtained. Used in the next step without further purification.

Reference Example 3 tert-butyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate 1- (2,6-diphenylisonicotinoyl) piperazine (28.79 g, 1- (tert-Butoxycarbonyl) -4-piperidone (16.70 g, 83 mmol) was added to a chloroform (amylene) solution (200 ml) of 83 mmol), and the mixture was stirred at room temperature for 30 minutes. Subsequently, sodium triacetoxyborohydride (35.53 g, 167 mmol) was added, and the mixture was stirred at room temperature for 7 hours. After completion of the reaction, 3M sodium hydroxide was added to make the reaction solution alkaline and extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, it was passed through silica gel column chromatography (methanol / chloroform) to obtain a crude product (44.27 g, quant) containing the title compound. The crude product was used in the next step without further purification.

Reference Example 4 1- (2,6-Diphenylisonicotinoyl) -4-piperidin-4-ylpiperazine
To a solution of tert-butyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate (26.19 g, 49 mmol) in methanol (140 ml), 4M hydrochloric acid-ethyl acetate solution (70 ml) was added and stirred at room temperature for 16 hours. After evaporating the solvent under reduced pressure, diethyl ether (150 ml) was added to the residue and stirred, and the precipitated hydrochloride was filtered off. A 2M aqueous sodium hydroxide solution was added to the chloroform suspension of the hydrochloride to make it alkaline, and the aqueous layer was separated. Further, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, the title compound (18.48 g, 87%.) Was obtained as a pale yellow amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.37-1.47 (m, 2 H), 1.80 (s, 2 H), 2.37-2.44 (m, 1 H), 2.53 (s, 2 H), 2.55- 2.62 (m, 2 H), 2.68-2.72 (m, 2 H), 3.15 (s, 2 H), 3.45 (s, 2 H), 3.85 (s, 2 H), 7.43-7.54 (m, 6 H ), 7.66 (s, 2 H), 8.13-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 427.3 [M + H] ⁺ .

Reference Example 5 8-Benzoyl-1,4-dioxa-8-azaspiro [4.5] decane
To a solution of 4-piperidone ethylene ketal (11.3 g, 78.9 mmol) and triethylamine (13.2 ml, 94.7 mmol) in chloroform (containing amylene) (200 ml), add benzoyl chloride (13.3 g, 94.7 mmol), and at room temperature for 1 hour Stir. The reaction solution was washed with 1M aqueous sodium hydroxide solution and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the crude product (24.07 g, quant.) Containing the title compound was used in the next step without further purification.
MS ESI (+): 248.2 [M + H] ⁺ , 270.1 [M + Na] ⁺ .
Reference Example 6 1-Benzoylpiperidin-4-one
To a solution of 8-benzoyl-1,4-dioxa-8-azaspiro [4.5] decane (24 g) in water / ethanol (1: 2) (150 ml) was added p-toluenesulfonic acid monohydrate (1.52 g, 8.0 mmol) was added and the reaction was carried out for 3 hours under reflux with heating. The reaction solvent was evaporated under reduced pressure, saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over magnesium sulfate and concentrated. The obtained crude product was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (11.5 g, 56.6 mmol) as a colorless oil.
MS ESI (+): 204.1 [M + H] ⁺ .
MS ESI (-): 202.0 [MH] ^- .

Reference Example 7 tert-butyl 4- (1-benzoylpiperidin-4-yl) piperazine-1-carboxylate
To a solution of 1-benzozoylpiperidin-4-one (11.5 g, 56.6 mmol) and 1- (tert-butoxycarbonyl) piperazine (10.6 g, 57 mmol) in chloroform (containing amylene) (143 ml), sodium triacetoxyborohydride (24 g, 113.2 mmol) was added and stirred at room temperature for 4 hours. After completion of the reaction, 3M sodium hydroxide was added to make the reaction solution alkaline. The organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, purification by silica gel column chromatography (methanol / chloroform) gave the title compound (14.83 g, 39.7 mmol, 70%) as a colorless oil.
MS ESI (+): 374.3 [M + H] ⁺ .
Reference Example 8 1- (1-Benzoylpiperidin-4-yl) piperazine
To a solution of tert-butyl 4- (1-benzoylpiperidin-4-yl) piperazine-1-carboxylate in methanol (200 ml) was added 4M hydrochloric acid-ethyl acetate solution (40 ml), and the mixture was stirred at room temperature for 2 days. After evaporating the solvent under reduced pressure, the residue was made alkaline with 3M aqueous sodium hydroxide solution, and extracted with chloroform. The obtained organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, purification by silica gel column chromatography (methanol / chloroform) gave the title compound (9.68 g, 36.06 mmol, 91%) as a pale yellow oil.
MS ESI (+): 274.1 [M + H] ⁺ .
Reference Example 9 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2-chloroquinoline
Other than using 2-chloroquinoline-4-carboxylic acid instead of 2,6-diphenylisonicotinic acid and 1- (1-benzoylpiperidin-4-yl) piperazine instead of 1- (tert-butoxycarbonyl) piperazine Carried out substantially the same reaction as in Reference Example 1 to obtain the title compound (1.79 g, 0.39 mmol, 78%).

Reference Example 10 1- (1-Benzoylpiperidin-4-yl) -4- (2,6-dichloroisonicotinoyl) piperazine
Oxalyl chloride (2.0 ml, 10.5 mmol) and N, N-dimethylformamide (1 drop) were added to a suspension of 2,6-dichloroisonicotinic acid in toluene (2.0 ml), and the mixture was stirred at 90 ° C. for 4 hours. The solvent was distilled off under reduced pressure to obtain 2,6-dichloroisonicotinic acid chloride. A suspension of 2,6-dichloroisonicotinic acid chloride obtained in the above procedure in chloroform (containing amylene) (17 ml) was treated with 1- (1-benzoylpiperidin-4-yl) piperazine (1.0 g, 3.66 mmol). And triethylamine (0.61 ml, 4.4 mmol) in chloroform (containing amylene) (37 ml) were added with ice cooling, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (1.6 g, 3.58 mmol, 98%) as a pale yellow amorphous.
MS ESI (+): 447 [M + H] ⁺ , 469 [M + Na] ⁺ .

Reference Example 11 tert-butyl 4- (2,6-dichloroisonicotinoyl) piperazine-1-carboxylate
The reaction was carried out in substantially the same manner as in Reference Example 1 except that 2,6-dichloroisonicotinic acid was used instead of 2,6-diphenylisonicotinic acid, and the title compound (28.4 g, 78.9 mmol, quant. ) Was obtained as a brown oil.
¹ H-NMR (200 MHz, CDCl ₃ ) δ 1.46-1.48 (s, 9 H), 3.25-3.60 (m, 6 H), 3.64-3.81 (m, 2 H), 7.24 (s, 2 H).
Reference Example 12 1- (2,6-Dichloroisonicotinoyl) piperazine
Other than using tert-butyl 4- (2,6-dichloroisonicotinoyl) piperazine-1-carboxylate instead of tert-butyl-4- (2,6-diphenylisonicotinoyl) piperazine-1-carboxylate Was carried out in substantially the same manner as in Reference Example 2 to obtain the title compound (16.9 g, 65.0 mmol, 83%) as a light brown solid.
¹ H NMR (200 MHz, CDCl ₃ ) δ 2.78-3.01 (m, 4 H), 3.32 (dd, J = 4.83, 3.96 Hz, 2 H), 3.72 (t, J = 4.83 Hz, 2 H), 7.24 (s, 2 H).
MS ESI / APCI Dual (+): 260.1 [M] ⁺ .

Reference Example 13 tert-butyl 4- [4- (2,6-dichloroisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
The reaction was carried out in substantially the same manner as in Reference Example 3 except that 1- (2,6-dichloroisonicotinoyl) piperazine was used instead of 1- (2,6-diphenylisonicotinoyl) piperazine. The compound (26.9 g, 60 mmol, 99%) was obtained as a pale yellow amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.51 (m, 11 H), 1.76 (d, J = 11.92 Hz, 2 H), 2.45 (tt, J = 11.35, 3.44 Hz, 1 H), 2.49-2.56 (m, 2 H), 2.60-2.79 (m, 4 H), 3.32-3.38 (m, 2 H), 3.70-3.79 (m, 2 H), 4.03-4.26 (m, 2 H), 7.24 (s, 2 H).
MS ESI / APCI Dual (+): 443.3 [M] ⁺ .
Reference Example 14 1- (2,6-Dichloroisonicotinoyl) -4-piperidin-4-ylpiperazine
tert-butyl 4- [4- (2,6-dichloroisonicotinoyl) piperazin-1-yl] piperidine-1-instead of tert-butyl-4- (2,6-diphenyl) piperazine-1-carboxylate The reaction was carried out substantially in the same manner as in Reference Example 2 except that carboxylate was used to give the title compound (20.6 g, 59.9 mmol, 99%) as a pale yellow amorphous product.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.44 (ddd, J = 24.19, 12.04, 4.13 Hz, 2 H), 1.77-1.83 (m, 2 H), 2.23 (br. S., 2 H), 2.42 (tt, J = 11.46, 3.67 Hz, 1 H), 2.53 (t, J = 4.81 Hz, 2 H), 2.61 (dt, J = 12.21, 2.41 Hz, 2 H), 3.15-3.20 (m, 2 H), 3.35 (t, J = 4.58 Hz, 2 H), 3.76 (t, J = 4.36 Hz, 2 H), 7.24 (s, 2 H).
MS ESI / APCI Dual (+): 343.1 [M] ⁺ .
Reference Example 15 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-dichloroisonicotinoyl) piperazine
Use 1- (2,6-dichloroisonicotinoyl) -4-piperidin-4-ylpiperazine instead of 4-piperidone ethylene ketal and 1-acetylpiperidine-4-carboxylic acid chloride hydrochloride instead of benzoyl chloride The reaction was carried out substantially in the same manner as in Reference Example 5 except that the title compound (1.51 g, 3.0 mmol, 30%) was obtained as a colorless amorphous.
MS ESI / APCI Dual (+): 496.1 [M + H] ⁺ .
Reference Example 16 1- (2,6-Dichloroisonicotinoyl) -4- {1-[(4-methoxycyclohexyl) carbonyl] -4-yl} piperazine
Substantially 1- (2,6-dichloroisonicotinoyl) -4-piperidin-4-ylpiperazine instead of 4-piperidone ethylene ketal and 4-methoxycyclohexanecarboxylic acid instead of benzoyl chloride The reaction was carried out in the same manner as in Reference Example 5 to obtain the title compound (1.89 g, 3.9 mmol, 39%) as a colorless amorphous.

Reference Example 17 tert-butyl 4-[(2-phenylquinolin-4-yl) carbonyl] piperazine-1-carboxylate
The title compound (5.7 g, quant) was colorless by carrying out the reaction in substantially the same manner as in Reference Example 1 except that 2-phenylquinoline-4-carboxylic acid was used instead of 2,6-diphenylisonicotinic acid. Obtained as amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.45 (s, 9 H), 3.14-3.42 (m, 4 H), 3.54-3.71 (m, 2 H), 3.80-3.93 (m, 1 H), 3.94-4.07 (m, 1 H), 7.44-7.62 (m, 4 H), 7.73-7.84 (m, 3 H), 8.11-8.26 (m, 3 H).
MS ESI / APCI Dual (+): 418.3 [M + H] ⁺ , 440.3 [M + Na] ⁺ .
Reference Example 18 2-Phenyl-4- (piperazin-1-ylcarbonyl) quinoline
tert-butyl 4-[(2-phenylquinolin-4-yl) carbonyl] piperazine-1-carboxylate instead of tert-butyl-4- (2,6-diphenylisonicotinoyl) piperazine-1-carboxylate The reaction was carried out in substantially the same manner as in Reference Example 2 except that it was used to obtain a crude product (4.3 g, quant.) Containing the title compound. Used in the next step without further purification.
MS ESI / APCI Dual (+): 318.2 [M + H] ⁺ .
MS ESI / APCI Dual (−): 317.0 [MH]-.

Reference Example 19 tert-butyl 4- {4-[(2-phenylquinolin-4-yl) carbonyl] piperazin-1-yl} piperidine-1-carboxylate
The reaction was carried out in substantially the same manner as in Reference Example 3 except that 2-phenyl-4- (piperazin-1-ylcarbonyl) quinoline was used instead of 1- (2,6-diphenylisonicotinoyl) piperazine. The title compound (5.4 g, 10.8 mmol, 79%) was obtained as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.30- 1.48 (m, 11 H), 1.69-1.88 (m, 2 H), 2.32-2.51 (m, 3 H), 2.61-2.81 (m, 4 H ), 3.18-3.28 (m, 2 H), 3.76-4.24 (m, 4 H), 7.45-7.61 (m, 4 H), 7.73-7.85 (m, 3 H), 8.13-8.24 (m, 3 H ).
MS ESI / APCI Dual (+): 501.3 [M + H] ⁺ , 523.3 [M + Na] ⁺ .
Reference Example 20 2-Phenyl-4-[(4-piperidin-4-ylpiperazin-1-yl) carbonyl] quinoline
tert-butyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate instead of tert-butyl 4- {4-[(2-phenylquinoline-4- Yl) carbonyl] piperazin-1-yl} piperidine-1-carboxylate, except that the title compound (4.20 g, 10.49 mmol, 97%) was purified in substantially the same manner as in Reference Example 4 Obtained as amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.29-1.46 (m, 2 H), 1.71-1.84 (m, 2 H), 2.31-2.49 (m, 3 H), 2.50-2.64 (m, 2 H ), 2.68-2.81 (m, 2 H), 3.07-3.18 (m, 2 H), 3.19-3.27 (m, 2 H), 3.85-4.08 (m, 2 H), 7.43-7.61 (m, 4 H ), 7.72-7.84 (m, 3 H), 8.11-8.24 (m, 3 H).
MS ESI / APCI Dual (+): 401.3 [M + H] ⁺ .

Reference Example 21 8- (morpholin-4-ylcarbonyl) -1,4-dioxa-8-azaspiro [4.5] decane
To a solution of 1,4-dioxa-8-azaspiro [4,5] decane (4.48 g, 31.3 mmol) in chloroform (containing amylene) (78 ml) was added triethylamine (3.17 g, 31.3 mmol) and 4-morpholinylcarbonyl chloride ( 4.40 g, 31.3 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was poured into water, and the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (8.43 g).
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.67-1.74 (m, 4 H), 3.25 (t, J = 4.82 Hz, 4 H), 3.32-3.40 (m, 4 H), 3.69 (t, J = 4.66 Hz, 4 H), 3.98 (s, 4 H).
MS ESI (+): 257.1 [M + H] ⁺ , 279 [M + Na] ⁺ .
Reference Example 22 1- (morpholin-4-ylcarbonyl) piperidin-4-one
Except for using 8- (morpholin-4-ylcarbonyl) -1,4-dioxa-8-azaspiro [4.5] decane instead of 8-benzoyl-1,4-dioxa-8-azaspiro [4.5] decane, Substantially the same reaction as in Reference Example 6 was carried out to give the title compound (4.28 g, 20.2 mmol, 64%) as a colorless oil.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 2.50 (t, J = 6.22 Hz, 4 H), 3.32-3.37 (m, 4 H), 3.56 (dd, J = 6.37, 6.06 Hz, 4 H), 3.69-3.75 (m, 4 H).
MS ESI (−): 211 [MH] ⁻ .

Reference Example 23 tert-butyl 4- [1- (morpholin-4-ylcarbonyl) piperidin-4-yl] piperazine-1-carboxylate
Except for using 1- (morpholin-4-ylcarbonyl) piperidin-4-one instead of 1-benzoylpiperidin-4-one, the reaction was carried out in substantially the same manner as in Reference Example 7 to give the title compound ( 5.5 g, 14.4 mmol, 72%) was obtained as a colorless solid.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.38-1.50 (m, 11 H), 1.76-1.86 (m, 2 H), 2.36-2.58 (m, 5 H), 2.70-2.83 (m, 2 H ), 3.24 (dd, J = 4.97, 4.51 Hz, 4 H), 3.42 (t, J = 4.66 Hz, 4 H), 3.68 (dd, J = 4.97, 4.51 Hz, 4 H), 3.71-3.80 (m , 2 H).
MS ESI (+): 383.3 [M + H] ⁺ , 405.3 [M + Na] ⁺ .
Reference Example 24 4-[(4-Piperazin-1-ylpiperidin-1-yl) carbonyl] morpholine
tert-butyl 4- [1- (morpholin-4-ylcarbonyl) piperidin-4-yl] piperazine-1- instead of tert-butyl 4- (1-benzoylpiperidin-4-yl) piperazine-1-carboxylate The title compound (3.07 g, 10.9 mmol, 76%) was obtained as a colorless solid by substantially the same reaction as in Reference Example 8 except that carboxylate was used.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.39-1.55 (m, 2 H), 1.78-1.89 (m, 2 H), 1.92-1.98 (m, 1 H), 2.37 (tt, J = 11.37, 3.69, 3.57 Hz, 1 H), 2.55 (t, J = 4.82 Hz, 2 H), 2.70-2.82 (m, 4H), 2.87-2.93 (m, 4 H), 3.24 (t, J = 4.82 Hz, 4 H), 3.68 (dd, J = 4.97, 4.66 Hz, 3 H), 3.71-3.81 (m, 2 H).
MS ESI (+): 283.2 [M + H] ⁺ .
Reference Example 25 Except for using 1-acetyl-4-piperidinecarboxylic acid chloride for 8-[(1-acetylpiperidin-4-yl) carbonyl] -1,4-dioxa-8-azaspiro [4.5] decanebenzoyl chloride Substantially the same reaction as in Reference Example 5 was performed to give the title compound (9.56 g, 32.2 mmol, 92%) as a white powder.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.61-1.77 (m, 7 H), 1.78-1.90 (m, 1 H), 2.10 (s, 3 H), 2.64-2.81 (m, 2 H), 3.07-3.16 (m, 1 H), 3.54-3.62 (m, 2 H), 3.64-3.76 (m, 2 H), 3.85-3.92 (m, 1 H), 3.95-4.03 (m, 4 H), 4.54-4.64 (m, 1 H).
MS ESI / APCI Dual (+): 297.0 [M + H] ⁺ , 318.9 [M + Na] ⁺ .

Reference Example 26 1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-one
8-[(1-acetylpiperidin-4-yl) carbonyl] -1,4-dioxa-8-azaspiro [4.5] decane instead of 8-benzoyl-1,4-dioxa-8-azaspiro [4.5] decane The title reaction (7.94 g, 31.4 mmol, 100%) was obtained as a colorless oil by substantially the same reaction as in Reference Example 6 except for using.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.66-1.82 (m, 4 H), 1.83-1.94 (m, 1 H), 2.11 (s, 3 H), 2.46-2.57 (m, 4 H), 2.67-2.76 (m, 1 H), 2.77-2.86 (m, 1 H), 3.08-3.20 (m, 1 H), 3.78-3.97 (m, 4 H), 4.59-4.65 (m, 1 H).
MS ESI / APCI Dual (+): 252.9 [M + H] ⁺ .
Reference Example 27 tert-Butyl 4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-carboxylate 1- [benzoylpiperidin-4-one instead of 1- [ The title compound (9.50 g, 22.5 mmol, 72%) was obtained by carrying out substantially the same reaction as in Reference Example 7 except that (1-acetylpiperidin-4-yl) carbonyl] piperidin-4-one was used. Obtained as a colorless oil.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.32-1.49 (m, 11 H), 1.60-1.77 (m, 4 H), 1.77-1.95 (m, 3 H), 2.10 (s, 3 H), 2.44-2.62 (m, 5 H), 2.65-2.78 (m, 2 H), 3.00-3.16 (m, 2 H), 3.38-3.47 (m, 4 H), 3.83-3.99 (m, 2 H), 4.53-4.69 (m, 2 H).
MS ESI / APCI Dual (+): 423.2 [M + H] ⁺ .

Reference Example 28 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine
tert-butyl 4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl instead of tert-butyl 4- (1-benzoylpiperidin-4-yl) piperazine-1-carboxylate } Except for using piperazine-1-carboxylate, a reaction was carried out substantially in the same manner as in Reference Example 8 to obtain the title compound (6.72 g, 20.8 mmol, 93%) as a pale yellow oil.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.32-1.50 (m, 2 H), 1.58-1.98 (m, 8 H), 2.10 (s, 3 H), 2.40-2.62 (m, 6 H), 2.64-2.78 (m, 2 H), 2.87-2.95 (m, 3 H), 3.00-3.15 (m, 2 H), 3.83-3.99 (m, 2 H), 4.52-4.70 (m, 2 H).
MS ESI / APCI Dual (+): 323.0 [M + H] ⁺ , 345.1 [M + Na] ⁺ .
Reference Example 29 tert-butyl 4- (9-anthrylcarbonyl) piperazine-1-carboxylate
An anthracene-9-carboxylic acid chloride was synthesized by the method described in the pamphlet of WO03 / 072197, and a reaction substantially similar to that of Reference Example 1 was carried out using this to produce a crude product containing the title compound (33.08 g ) Was obtained as a light brown solid.
MS ESI (+): 444.3 [M + H] ⁺ .
Reference Example 30 1- (9-anthrylcarbonyl) piperazine
Substantially Reference Example except that tert-butyl 4- (9-anthrylcarbonyl) piperazine-1-carboxylate is used instead of tert-butyl-4- (2,6-diphenyl) piperazine-1-carboxylate The reaction was carried out in the same manner as 2 to obtain the title compound (14.6 g, 50.3 mmol, 90%) as a light brown solid.
MS ESI (+): 291.1 [M + H] ⁺ .
Reference Example 31 tert-butyl 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidine-1-carboxylate
The reaction was carried out in substantially the same manner as in Reference Example 3 except that 1- (9-anthrylcarbonyl) piperazine was used instead of 1- (2,6-diphenylisonicotinoyl) piperazine, and the title compound ( 10.3 g, quant.) Was obtained as a light brown oil.
MS ESI (+): 474.3 [M + H] ⁺ , 496.3 [M + H] ⁺ .
Reference Example 32 1- (9-anthrylcarbonyl) -4-piperidin-4-ylpiperazine
tert-butyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate instead of tert-butyl 4- [4- (9-anthrylcarbonyl) piperazine- The reaction was carried out in substantially the same manner as in Reference Example 4 except that 1-yl] piperidine-1-carboxylate was used to obtain the title compound (5.88 g, 15.74 mmol, 79%) as a light brown solid. .
MS ESI (+): 427.3 [M + H] ⁺ .

Reference Example 33 tert-Butyl 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] azepan-1-carboxylate 4-oxoazepane-1-carboxylate instead of 1-Boc-4-piperidone The reaction was carried out substantially in the same manner as in Reference Example 3 except that butyl ester was used to obtain a crude product (2.9 g) containing the title compound as a brown oily substance.
MS ESI (+): 488.2 [M + H] ⁺ .
Reference Example 34 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] azepane
tert-butyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate instead of tert-butyl 4- [4- (9-anthrylcarbonyl) piperazine- The reaction was carried out in substantially the same manner as in Reference Example 4 except that 1-yl] azepan-1-carboxylate was used to obtain a crude product (1.8 g) containing the title compound as a brown oily substance.
MS ESI (+): 388.3 [M + H] ⁺ .
Reference Example 35 2-Methoxy-6-phenylisonicotinic acid under an argon atmosphere, 2-chloro-6-methoxyisonicotinic acid (188 mg, 1.0 mmol), phenylboronic acid (122 mg, 1.0 mmol), tetrakistriphenylphosphine palladium ( 0) (12 mg, 0.050 mmol), a suspension of sodium carbonate (233 mg, 2.2 mmol) in dimethoxyethane / water / ethanol (7: 3: 2, 2 ml) was stirred at 150 ° C. for 15 minutes under microwave irradiation. The reaction solution was neutralized with a saturated aqueous ammonium chloride solution and extracted with chloroform. A 1 M aqueous hydrochloric acid solution was added to the aqueous layer to adjust the pH to 1-2, followed by extraction with chloroform. The combined organic layers were washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give the title compound (194 mg, 0.85 mmol, 85%.) As a pale red powder.
¹ H-NMR (300 MHz, DMSO-d ₆ ) δ 4.01 (s, 3 H), 7.43-7.57 (m, 4 H), 7.90 (d, J = 1.09Hz, 1 H), 8.09-8.18 (m , 2 H).
MS ESI (−): 228.0 [MH]-.

Reference Example 36 2,6-dichlorophenylisonicotinic acid (1.15 g, 6.0 mmol), phenylboronic acid (693 mg, 5.7 mmol), tetrakistriphenylphosphine palladium (0 ) (348 mg, 0.03 mmol), sodium carbonate (1.40 g, 13.2 mmol) in ethanol / dimethoxyethane / water (3: 2: 1, 1.5 ml) was stirred at 150 ° C. for 20 minutes under microwave irradiation. . Chloroform was added to the reaction solution, and the organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. Concentration under reduced pressure, and the resulting residue was purified by silica gel column chromatography (methanol / chloroform) to obtain a crude product (540 mg) containing the title compound as a colorless solid.
MS ESI (+): 234.1 [M + H] ⁺ .
Reference Example 37 1- (1-Benzoylpiperidin-4-yl) -4- (2-chloro-6-phenylisonicotinoyl) piperazine
To a solution of crude product containing 2-chloro-6-phenylisonicotinic acid (500 mg, 2.14 mmol) in toluene (2.0 ml) was added oxalyl chloride (2.0 ml) and N, N-dimethylformamide (1 drop), Stir at 90 ° C. for 4 hours. The solvent was distilled off under reduced pressure to obtain 2-chloro-6-phenylisonicotinic acid chloride.
The obtained 2-chloro-6-phenylisonicotinic acid chloride was mixed with 1- (1-benzoylpiperidin-4-yl) piperazine (Reference Example 8) (585 mg, 2.14 mmol) and triethylamine (260 mg, 2.57 mmol) in chloroform. (Amylene) (22 ml) was added to the solution and stirred at room temperature for 1 hour. The reaction solution was poured into 1M aqueous sodium hydroxide solution, and the organic layer was washed with water and saturated brine. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (methanol / chloroform), and the title compound and 1- (1-benzoylpiperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine (Example) A 4: 1 mixture (1.17 g) with 46) was obtained as a pale yellow amorphous.
MS ESI (+): 489.2 [M + H] ⁺ .

Reference Example 38 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6-phenylisonicotinoyl) piperazine
Except for using 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine instead of 1- (1-benzoylpiperidin-4-yl) piperazine The reaction was carried out in the same manner as in Reference Example 37, and the title compound and 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-dichloroisonicotinoyl) ) A 2: 1 mixture (361 mg) with piperazine was obtained as a pale yellow amorphous.
MS ESI (+): 538.2 [M + H] ⁺ .
Reference Example 39 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6-phenylisonicotinoyl) piperazine
According to the method described in Helvetica Chim. Acta., 118, 1033, 1955. 2-chloro-6-phenylisonicotinic acid chloride was obtained. The obtained 2-chloro-6-phenylisonicotinic acid chloride (6.7 g) was converted into 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine (Reference Example 28). (7.42 g, 23.0 mmol) and triethylamine (6.4 ml, 46.0 mmol) in chloroform (containing amylene) (230 ml) were added and stirred at room temperature for 1 hour. The reaction solution was poured into 1M aqueous sodium hydroxide solution, and the organic layer was washed with water and saturated brine. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (4.49 g, 8.34 mmol, 47%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.46 (m, 2 H), 1.57-1.75 (m, 3 H), 1.76-1.94 (m, 3 H), 2.08 (s, 3 H) , 2.45-2.61 (m, 4 H), 2.61-2.75 (m, 4 H), 3.01-3.14 (m, 2 H), 3.36-3.44 (m, 2 H), 3.74-3.83 (m, 2 H) , 3.83-3.90 (m, 1 H), 3.91-4.00 (m, 1 H), 4.50-4.60 (m, 1 H), 4.61-4.70 (m, 1 H), 7.21 (s, 1 H), 7.43 -7.50 (m, 3 H), 7.60 (s, 1 H), 7.95-8.01 (m, 2 H).
MS ESI / APCI Dual (+): 538.3 [M + H] ⁺ .
Reference Example 40 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6- (4-methylphenyl) isonicotinoyl) piperazine
Reference using 2-chloro-6- (4-methylphenyl) isonicotinic acid chloride and 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine (Reference Example 28) A reaction substantially similar to Example 39 was performed to give the title compound.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.47 (m, 2 H), 1.59-1.75 (m, 3 H), 1.76-1.94 (m, 3 H), 2.08 (s, 3 H) , 2.40 (s, 3 H), 2.46-2.60 (m, 4 H), 2.61-2.75 (m, 4 H), 3.00-3.14 (m, 2 H), 3.35-3.43 (m, 2 H), 3.74 -3.83 (m, 2 H), 3.84-3.90 (m, 1 H), 3.92-3.99 (m, 1 H), 4.52-4.60 (m, 1 H), 4.61-4.68 (m, 1 H), 7.17 (s, 1 H), 7.25-7.29 (m, 2 H), 7.57 (s, 1 H), 7.86-7.91 (m, 2 H).
MS ESI / APCI Dual (+): 552.3 [M + H] ⁺ .

Reference Example 41
1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6- (1H-indol-5-yl) isonicotinoyl) piperazine
Using 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-indole, a substantially similar reaction as in Reference Example 36 was carried out, and 2-chloro A mixture containing -6- (1H-indol-5-yl) isonicotinic acid was obtained. The resulting mixture of 2-chloro-6- (1H-indol-5-yl) isonicotinic acid (1.87 g), 1- {1-[(1-acetylpiperidin-4-yl) obtained in Example 28 ) Carbonyl] piperidin-4-yl} piperazine (1.62 g, 5.0 mmol) and HOBt · H 2 O (0.88 g, 6.5 mmol) in chloroform (containing amylene) (50 ml) with EDC · HCI (1.25 g, 6.5 mmol) In addition, the mixture was stirred overnight at room temperature. The reaction mixture was washed with saturated aqueous sodium hydrogen carbonate solution and saturated brine, and then purified successively with NH silica gel column chromatography (methanol / chloroform) and silica gel column chromatography (methanol / chloroform) to give the title compound (1.776 g, 3.1 mmol, 62%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.48 (m, 2 H), 1.58-1.77 (m, 3 H), 1.77-1.95 (m, 3 H), 2.09 (s, 3 H) , 2.46-2.62 (m, 4 H), 2.62-2.77 (m, 4 H), 3.01-3.15 (m, 2 H), 3.37-3.50 (m, 2 H), 3.74-3.92 (m, 3 H) , 3.92-4.02 (m, 1 H), 4.51-4.62 (m, 1 H), 4.61-4.71 (m, 1 H), 6.62-6.65 (m, 1 H), 7.14-7.16 (m, 1 H) , 7.25-7.28 (m, 1 H), 7.46 (d, J = 8.25 Hz, 1 H), 7.65 (s, 1 H), 7.87 (d, J = 8.71 Hz, 1 H), 8.30-8.33 (m , 1 H), 8.45 (br. S., 1 H).
MS ESI / APCI Dual (+): 577.3 [M + H] ⁺ .
Example 1 tert-Butyl 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1-carboxylate
1- (2,6-diphenylisonicotinoyl) -4-piperidin-4-ylpiperazine (10.0 g, 23.44 mmol), 1- (tert-butoxycarbonyl) piperidine-4-carboxylic acid (8.06 g, 35.16 mmol) To a solution of HOBt · H ₂ O (4.76 g, 35.16 mmol) in chloroform (containing amylene) (78 ml) was added EDC · HCI (6.74 g, 35.16 mmol), and the mixture was stirred overnight at room temperature. The reaction solution was washed with a saturated aqueous sodium hydrogen carbonate solution and dried over anhydrous magnesium sulfate. After concentration, purification by silica gel column chromatography (methanol / chloroform) gave the title compound (13.76 g, 21.57 mmol, 92%).
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.48 (m, 11 H), 1.58-1.79 (m, 4 H), 1.81-1.94 (m, 2 H), 2.45-2.84 (m, 9 H ), 2.99-3.09 (m, 1 H), 3.41-3.50 (m, 2 H), 3.80-3.89 (m, 2 H), 3.92-4.00 (m, 1 H), 4.03-4.25 (m, 2 H ), 4.62-4.70 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 638.4 [M + H] ⁺ , 660.4 [M + Na] ⁺ .

Example 2 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
1- (2,6-diphenylisonicotinoyl) -4-piperidin-4-ylpiperazine (2.34 g, 5.5 mmol), triethylamine (1.55 ml, 11.0 mmol) in chloroform (containing amylene) (30 ml) in 1- Acetylpiperidine-4-carbonyl chloride (1.49 g) was added, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (3.00 g, 5.17 mmol, 94%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.47 (m, 2 H), 1.56-1.75 (m, 3 H), 1.75-1.94 (m, 3 H), 2.08 (s, 3 H), 2.45-2.60 (m, 4 H), 2.62-2.74 (m, 4 H), 3.01-3.13 (m, 2 H), 3.44 (s, 2 H), 3.79-3.90 (m, 3 H), 3.95 ( dd, J = 12.49, 1.03 Hz, 1 H), 4.52-4.60 (m, 1 H), 4.65 (d, J = 13.07 Hz, 1 H), 7.43-7.48 (m, 2 H,) 7.48-7.53 ( m, 4 H), 7.64 (s, 2 H), 8.11-8.16 (m, 4 H).
MS ESI / APCI Dual (+): 580.3 [M + H] ⁺ .
Example 3 4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -2-methoxyphenol
1- (2,6-diphenylisonicotinoyl) -4-piperidin-4-ylpiperazine (100 mg, 0.234 mmol), vanillic acid (59 mg, 0.351 mmol), HOBt · H2O (54 mg, 0.351 mmol) in chloroform (including EDC · HCl (67 mg, 0.351 mmol) was added to a solution of (amylene) (2.0 ml), and the mixture was stirred at room temperature for 18 hours. The reaction mixture was washed with 1M aqueous sodium hydroxide solution and saturated brine, and purified by silica gel column chromatography (methanol / chloroform) to give the title compound (116 mg, 0.201 mmol, 86%) as a colorless amorphous product.
MS ESI / APCI Dual (+): 577.4 [M + H] ⁺ .

Example 4 Substantially except that 4-fluorobenzoic acid is used instead of 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-fluorobenzoyl) piperidin-4-yl] piperazine vanillic acid Specifically, the reaction was carried out in the same manner as in Example 3 to obtain the title compound (64 mg, quant.) As a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.31-1.64 (m, 2 H), 1.67-2.09 (m, 2 H), 2.40-3.20 (m, 7 H), 3.35-3.58 (m, 2 H ), 3.67-3.98 (m, 3 H), 4.62-4.85 (m, 1 H), 7.05-7.19 (m, 3 H), 7.32-7.56 (m, 7 H), 7.62-7.68 (m, 2 H ), 8.09-8.20 (m, 4 H).
MS ESI / APCI Dual (+): 549.2 [M + H] ⁺ , 571.2 [M + Na] ⁺ .
MS ESI / APCI Dual (−): 547.2 [MH] ⁻ .
Example 5 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-methyl-1H-pyrrol-2-yl) carbonyl] piperidin-4-yl} piperazine 1 instead of vanillic acid The reaction was carried out in substantially the same manner as in Example 3 except that -methyl-2-pyrrolecarboxylic acid was used to obtain the title compound (82 mg, 0.153 mmol, 77%) as a colorless amorphous.
MS ESI / APCI Dual (+): 534.5 [M + H] ⁺ , 556.4 [M + Na] ⁺ .

Example 6 1- (2,6-Diphenylisonicotinoyl) -4- {1-[(1-methylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine instead of vanillic acid 1-methyl- The reaction was carried out substantially in the same manner as in Example 3 except that piperidine-4-carboxylic acid was used to obtain the title compound (80 mg, 0.145 mmol, 73%) as a colorless amorphous.
MS ESI / APCI Dual (+): 552.5 [M + H] ⁺ .
Example 7 4- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -N, N-dimethyl-4-oxobutan-1-aminevanillic acid The reaction was carried out substantially in the same manner as in Example 3 except that 4-dimethylaminobutyric acid was used instead to obtain the title compound (83 mg, 0.153 mmol, 78%) as a colorless amorphous.
MS ESI / APCI Dual (+): 540.6 [M + H] ⁺ .
Example 8 Instead of 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclohexanol vanillic acid, 4-hydroxycyclohexanecarboxylic acid was used. The reaction was carried out substantially in the same manner as in Example 3 except for using, to give the title compound (49 mg, 0.089 mmol, 38%) as a colorless amorphous.
MS ESI / APCI Dual (+): 553.5 [M + H] ⁺ _.

Example 9 [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclohexyl] methanol instead of vanillic acid 4-hydroxymethylcyclohexane The reaction was carried out substantially in the same manner as in Example 3 except that carboxylic acid was used to obtain the title compound (90 mg, 0.159 mmol, 68%) as a colorless amorphous.
MS ESI / APCI Dual (+): 567.5 [M + H] ⁺ , 589.5 [M + Na] ⁺ .
Example 10 [(1R, 2R) -2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclohexyl] (phenyl) methanone The reaction was carried out in substantially the same manner as in Example 3 except that trans-2-benzoyl-1-cyclohexanecarboxylic acid was used instead of vanillic acid to give the title compound (81 mg, 0.126 mmol, 54%) as a colorless amorphous Got as.
MS ESI / APCI Dual (+): 641.5 [M + H] ⁺ .
Example 11 4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol 4-hydroxybenzoic acid is used instead of vanillic acid The title compound (34 mg, 0.063 mmol, 27%) was obtained as a colorless amorphous substance substantially in the same manner as in Example 3 except for the above.
MS ESI / APCI Dual (+): 547.4 [M + H] ⁺ .
Example 12 [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] methanol instead of vanillic acid 4-hydroxymethylbenzoate The reaction was carried out in substantially the same manner as in Example 3 except that the acid was used to give the title compound (64 mg, 0.114 mmol, 49%) as a colorless amorphous product.
MS ESI / APCI Dual (+): 561.5 [M + H] ⁺ , 583.4 [M + Na] ⁺ .
Example 13 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl)-N, N-dimethylaniline instead of vanillic acid 4- The reaction was carried out substantially in the same manner as in Example 3 except that dimethylaminobenzoic acid was used to obtain the title compound (107 mg, 0.198 mmol, 80%) as a pale yellow amorphous.
MS ESI / APCI Dual (+): 574.5 [M + H] ⁺ .

Example 14 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-methylaniline instead of vanillic acid 4-methylamino The reaction was carried out in substantially the same manner as in Example 3 except that benzoic acid was used to obtain the title compound (102 mg, 0.182 mmol, 78%) as a pale yellow amorphous.
MS ESI / APCI Dual (+): 560.5 [M + H] ⁺ .
Example 15 1- (2,6-Diphenylisonicotinoyl) -4- {1- [4- (4-methylpiperazin-1-yl) benzoyl] piperidin-4-yl} piperazine instead of vanillic acid 4- The reaction was carried out substantially in the same manner as in Example 3 except that (4-methylpiperazino) benzoic acid was used to obtain the title compound (130 mg, 0.206 mmol, 88%) as a pale yellow amorphous.
MS ESI / APCI Dual (+): 629.5 [M + H] ⁺ .
Example 16 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-furoyl) piperidin-4-yl] piperazine Substantially except that 3-furancarboxylic acid is used instead of vanillic acid The reaction was carried out in the same manner as in Example 3 to obtain the title compound (120 mg, 0.230 mmol, 98%) as a colorless amorphous.
MS ESI / APCI Dual (+): 521.4 [M + H] ⁺ .
Example 17 4-Pyrazolecarboxylic acid is used in place of 1- (2,6-diphenylisonicotinoyl) -4- [1- (1H-pyrazol-4-ylcarbonyl) piperidin-4-yl] piperazinevanillic acid The title compound (120 mg, quant.) Was obtained as a colorless amorphous substance by carrying out the reaction substantially in the same manner as in Example 3 except that.
MS ESI / APCI Dual (+): 521.5 [M + H] ⁺ .
Example 18 1- (2,6-Diphenylisonicotinoyl) -4- {1-[(1-methylcyclopropyl) carbonyl] piperidin-4-yl} piperazine instead of vanillic acid 1-methylcyclopropanecarboxylic acid The title compound (116 mg, 0.228 mmol, 97%) was obtained as a colorless amorphous substance by carrying out the reaction substantially in the same manner as in Example 3 except that
¹ H-NMR (600 MHz, CDCl ₃ ) δ 0.53-0.59 (m, 2 H), 0.84-0.95 (m, 2 H), 1.29 (s, 3 H), 1.35-1.47 (m, 2 H), 1.79-1.92 (m, 2 H), 2.41-2.61 (m, 4 H), 2.62-2.96 (m, 3 H), 3.39-3.51 (m, 2 H), 3.78-3.90 (m, 2 H), 4.41-4.57 (m, 2 H), 7.43-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 509.5 [M + H] ⁺ .

Example 19 1- (2,6-diphenylisonicotinoyl) -4- [1- (isoxazol-5-ylcarbonyl) piperidin-4-yl] piperazine vanillic acid instead of isoxazole-5-carboxylic acid The reaction was carried out in substantially the same manner as in Example 3 except for using the title compound (70 mg, 0.113 mmol, 57%) as a colorless amorphous substance.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.49-1.72 (m, 2 H), 1.86-2.00 (m, 2 H), 2.48-2.56 (m, 2 H), 2.59-2.66 (m, 1 H ), 2.66-2.75 (m, 2 H), 2.80-2.89 (m, 1 H), 3.11-3.21 (m, 1 H), 3.41-3.51 (m, 2 H), 3.79-3.91 (m, 2 H ), 4.18-4.26 (m, 1 H), 4.64-4.72 (m, 1 H), 6.75 (d, J = 1.37 Hz, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.55 (m , 4 H), 7.65 (s, 2 H), 8.12-8.18 (m, 4 H), 8.31 (d, J = 1.83 Hz, 1 H).
MS ESI / APCI Dual (+): 522.5 [M + H] ⁺ , 544.4 [M + Na] ⁺ .
Example 20 trans-4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclohexanol instead of vanillic acid trans-4-hydroxy The reaction was carried out in substantially the same manner as in Example 3 except that cyclohexanecarboxylic acid was used to obtain the title compound (91 mg, 0.165 mmol, 70%) as a colorless amorphous.
MS ESI / APCI Dual (+): 553.5 [M + H] ⁺ .
Example 21 3- {4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2,2-dimethyl-3-oxopropan-1-olvanillic acid The reaction was carried out substantially in the same manner as in Example 3 except that hydroxypivalic acid was used instead of to give the title compound (27 mg, 0.051 mmol, 22%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.27 (s, 6 H), 1.38-1.48 (m, 2 H), 1.85-1.92 (m, 2 H), 2.47-2.58 (m, 3 H), 2.65-2.72 (m, 2 H), 2.72-2.87 (m, 2 H), 3.41-3.50 (m, 4 H), 3.65-3.71 (m, 1 H), 3.80-3.90 (m, 2 H), 4.36-4.51 (m, 2 H), 7.44-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 527.3 [M + H] ⁺ .

Example 22 4-methyl-cyclohexanecarboxylic acid instead of 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methylcyclohexyl) carbonyl] piperidin-4-yl} piperazine vanillic acid The reaction was carried out in substantially the same manner as in Example 3 except for using the title compound (123 mg, 0.223 mmol, 95%) as a colorless amorphous substance.
MS ESI / APCI Dual (+): 551.3 [M + H] ⁺ .
Example 23 1- (2,6-Diphenylisonicotinoyl) -4- [1- (tetrahydro-2H-pyran-4-ylcarbonyl) piperidin-4-yl] piperazine Vanillic acid instead of tetrahydropyran-4- The reaction was carried out in substantially the same manner as in Example 3 except that yl-carboxylic acid was used to obtain the title compound (121 mg, 0.225 mmol, 96%) as a light brown amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.47 (m, 2 H), 1.53-1.68 (m, 2 H), 1.83-1.96 (m, 4 H), 2.46-2.60 (m, 4 H ), 2.64-2.77 (m, 3 H), 3.00-3.08 (m, 1 H), 3.40-3.49 (m, 4 H), 3.80-3.91 (m, 2 H), 3.93-4.05 (m, 3 H ), 4.64-4.72 (m, 1 H), 7.44-7.49 (m, 2H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 539.3 [M + H] ⁺ .
Example 24 Methyl 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoate instead of vanillic acid mono-methyl-terephthalic acid The reaction was carried out substantially in the same manner as in Example 3 except for using, to give the title compound (413 mg, 0.72 mmol, quant.) As a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.37-1.49 (m, 1 H), 1.54-1.61 (m, 1 H), 1.74-1.82 (m, 1 H), 1.92-2.01 (m, 1 H ), 2.49-2.61 (m, 3 H), 2.66-2.75 (m, 2 H), 2.77-2.86 (m, 1 H), 2.97-3.07 (m, 1 H), 3.42-3.50 (m, 2 H ), 3.67-3.76 (m, 1H), 3.80-3.90 (m, 2 H), 3.94 (s, 3 H), 4.71-4.80 (m, 1 H), 7.43-7.49 (m, 4 H), 7.49 -7.54 (m, 4 H), 7.65 (s, 2 H), 8.06-8.09 (m, 2 H), 8.13-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 588.3 [M + H] ⁺ .

Example 25 4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoic acid Methyl 4-({ 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoate (397 mg, 0.67 mmol) in methanol (3.5 ml) solution in 1M aqueous sodium hydroxide solution (1.3 ml) was added and stirred at room temperature overnight. The solvent was evaporated under reduced pressure, 1M aqueous hydrochloric acid solution was added to the residue, and the mixture was extracted with chloroform. The aqueous layer was extracted with chloroform, and the combined organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (125 mg, 0.218 mmol, 32%).
MS ESI / APCI Dual (+): 575.2 [M + H] ⁺ .
Example 26 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N, N-dimethylbenzamide
4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoic acid (86 mg, 0.143 mmol) and dimethylamine hydrochloride (23 mg, 0.286 mmol), triethylamine (40 μl, 0.286 mmol), HOBt · H ₂ O (44 mg, 0.286 mmol) in chloroform (containing amylene) (1.0 ml) and EDC · HCl (55 mg, 0.286 mmol) were added at room temperature. Stir overnight. The reaction mixture was washed with 1M aqueous sodium hydroxide solution and saturated brine, and purified by preparative TLC (10% methanol / chloroform) to give the title compound (66 mg, 0.11 mmol, 77%) as a colorless amorphous product.
MS ESI / APCI Dual (+): 602.3 [M + H] ⁺ .

Example 27 4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-methylbenzamide dimethylamine instead of methylamine hydrochloride The reaction was carried out in substantially the same manner as in Example 26 except that hydrochloride was used to obtain the title compound (56 mg, quant.) As a colorless amorphous. MS ESI / APCI Dual (+): 588.3 [M + H] ⁺ .
Example 28 4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzonitrile 1- (2, 6-diphenylisonicotinoyl) -4-piperidin-4-yl] piperazine (153 mg, 0.37 mmol), triethylamine (65 μl, 0.47 mmol) in chloroform (amylene) (1.0 ml) in 4-cyanobenzoyl chloride (74 mg) , 0.45 mmol), and stirred at room temperature for 1 hour. The reaction solution was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (189 mg, 0.34 mmol, 92%) as a pale yellow amorphous.
MS ESI / APCI Dual (+): 556.3 [M + H] ⁺ .
Example 29 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzamide
4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzonitrile (189 mg, 0.34 mmol) in 20% potassium hydroxide suspension (4 ml) was dissolved in THF (1 ml) / ethanol (2 ml). To this mixture was added 30% aqueous hydrogen peroxide (1 ml), and the mixture was heated to reflux for 4 hours. The reaction mixture was poured into water and extracted with ethyl acetate (50 ml). The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (36 mg, 0.063 mmol, 18%) as a colorless amorphous.
MS ESI / APCI Dual (+): 574.3 [M + H] ⁺ .

Example 30 4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclohexanone instead of vanillic acid 4-oxocyclohexanecarboxylic acid The reaction was carried out substantially in the same manner as in Example 3 except that the title compound (100 mg, 0.182 mmol, 78%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.38-1.52 (m, 2 H), 1.85-1.98 (m, 2 H), 1.98-2.09 (m, 4 H), 2.31-2.40 (m, 2 H ), 2.48-2.64 (m, 6 H), 2.67-2.73 (m, 2 H), 2.91-2.97 (m, 1 H), 3.07-3.15 (m, 1 H), 3.43-3.50 (m, 2 H ), 3.81-3.91 (m, 2 H), 3.98-4.06 (m, 1 H), 4.65-4.72 (m, 1 H), 7.45-7.49 (m, 2 H), 7.50-7.54 (m, 4 H ), 7.66 (s, 2 H), 8.14-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 550.3 [M + H] ⁺ .
Example 31 tert-Butyl (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1,1-dimethyl-2-oxoethyl) carbamate vanillin The reaction was carried out in substantially the same manner as in Example 3 except that 2-tert-butoxycarbonyl-2-aminoisobutyric acid was used in place of the acid to give the title compound (99 mg, 0.162 mmol, 69%) as a colorless amorphous substance. Obtained. MS ESI / APCI Dual (+): 612.3 [M + H] ⁺ .

Example 32 1- {4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-methyl-1-oxopropan-2-amine trihydrochloride
tert-Butyl (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1,1-dimethyl-2-oxoethyl) carbamate (98 mg, 0.19 mmol) in methanol (2 ml) was added 4M hydrochloric acid-ethyl acetate solution (1.0 ml) and stirred at room temperature overnight. The solvent was distilled off under reduced pressure to obtain the title compound (83 mg, 0.143 mmol, 71%) as a colorless amorphous.
MS ESI / APCI Dual (+): 512.3 [M + H] ⁺ .
Example 33 N- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1,1-dimethyl-2-oxoethyl) acetamide Example 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-methyl-1-oxopropan-2-amine obtained in 32 Triethylamine (56 μl, 0.4 mmol) and acetic anhydride (13 mg, 0.12 mmol) were added to a suspension of salt (50 mg, 0.08 mmol) in THF (2.0 ml), and the mixture was stirred at room temperature for 18 hours. The reaction mixture was poured into water, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (33 mg, 0.06 mmol, 75%) as a colorless amorphous.
MS ESI / APCI Dual (+): 554.3 [M + H] ⁺ .
Example 34 1- {1-[(4,4-Difluorocyclohexyl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine Vanillic acid instead of 4,4-difluorocyclohexane The reaction was carried out substantially in the same manner as in Example 3 except that carboxylic acid was used to obtain the title compound (132 mg, 0.23 mmol, 98%) as a colorless amorphous.
MS ESI / APCI Dual (+): 573.2 [M + H] ⁺ .

Example 35 [3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] methanol instead of vanillic acid 3-hydroxymethylbenzoate The reaction was carried out in substantially the same manner as in Example 3 except that the acid was used to obtain the title compound (145 mg, 0.259 mmol, 92%) as a colorless amorphous.
MS ESI / APCI Dual (+): 561.4 [M + H] ⁺ .
Example 36 2- [4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] -2-oxoethyl acetate instead of vanillic acid The reaction was carried out in substantially the same manner as in Example 3 except that 4- (α-acetoxyacetyl) benzoic acid was used to give the title compound (219 mg, 0.347 mmol, 74%) as a pale yellow amorphous product.
MS ESI / APCI Dual (+): 631.4 [M + H] ⁺ .
Example 37 1- [4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] -2-hydroxyethanone Example 36 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] -2-oxoethyl acetate (219 mg, To a solution of 0.347 mmol) in THF / MeOH (1: 1, 3.0 ml) was added a solution of sodium methoxide (21 mg, 0.381 mmol) in MeOH (1 ml) and stirred at room temperature overnight. The system was neutralized with dry ice and concentrated. The residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (20 mg, 0.034 mmol, 10%) as a colorless amorphous.
MS ESI / APCI Dual (+): 589.4 [M + H] ⁺ .
Example 38 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-methylaniline instead of vanillic acid 4- (methyl The reaction was carried out in substantially the same manner as in Example 3 except that amino) benzoic acid was used to obtain the title compound (119 mg, 0.21 mmol, 91%) as a colorless amorphous.
MS ESI / APCI Dual (+): 560.4 [M + H] ⁺ .

Example 39 N- [4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] -N-methylacetamide in Example 38 The resulting 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-methylaniline (110 mg, 0.197 mmol) in THF ( To the 2.0 ml) solution was added acetic anhydride (40 mg, 0.393 mmol) and stirred at room temperature overnight. The solvent was replaced with chloroform (2.0 ml), copper (I) trifluoromethanesulfonate benzene complex (5 mg, 0.01 mmol) was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by preparative TLC (10% methanol / chloroform) to obtain the title compound (87 mg, 0.145 mmol, 73%) as a colorless amorphous.
MS ESI / APCI Dual (+): 602.4 [M + H] ⁺ .
Example 40 Instead of 1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] pyrrolidin-2-one vanillic acid The reaction was carried out in substantially the same manner as in Example 3 except that 4- (2-oxo-pyrrolidin-1-yl) benzoic acid was used to give the title compound (104 mg, 0.169 mmol, 72%) as a colorless amorphous product. Obtained.
MS ESI / APCI Dual (+): 614.3 [M + H] ⁺ .
Example 41 2- [4-({4- [4- (2,6-Diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenoxy] ethanol instead of vanillic acid 4- ( The reaction was carried out in substantially the same manner as in Example 3 except that 2-hydroxyethoxy) benzoic acid was used to give the title compound (94 mg, 0.159 mmol, 68%) as a colorless amorphous.
MS ESI / APCI Dual (+): 591.4 [M + H] ⁺

Example 42 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] ethanol instead of vanillic acid 4- ( The reaction was carried out in substantially the same manner as in Example 3 except that 2-hydroxyethyl) benzoic acid was used to obtain the title compound (78 mg, 0.136 mmol, 58%) as a colorless amorphous.
MS ESI / APCI Dual (+): 575.4 [M + H] ⁺
Example 43 N- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] acetamido 4-acetamide instead of vanillic acid The reaction was carried out substantially in the same manner as in Example 3 except that benzoic acid was used to obtain the title compound (88 mg, 0.15 mmol, 64%) as a colorless amorphous.
MS ESI / APCI Dual (+): 588.4 [M + H] ⁺
Example 44 1- (2,6-diphenylisonicotinoyl) -4-{[1-[(4-piperidin-1-yl) benzoyl)] piperidin-4-yl]} piperazine instead of vanillic acid 4- The reaction was carried out substantially in the same manner as in Example 3 except that piperidone benzoic acid was used to obtain the title compound (61 mg, 0.099 mmol, 42%) as a colorless amorphous.
MS ESI / APCI Dual (+): 614.4 [M + H] ⁺
Example 45 1- [1- (2,2-Dimethylpropanoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine 1-[(2, 6-Diphenylisonicotinoyl) -4-piperidin-4-yl] piperazine (100 mg, 0.234 mmol), triethylamine (65 μl, 0.47 mmol) in chloroform (amylene) (2.0 ml) in pivaloyl chloride (57 mg, 0.47 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (65 mg, 0.127 mmol, 54%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.26 (s, 9 H), 1.36-1.45 (m, 2 H), 1.81-1.87 (m, 2 H), 2.47-2.55 (m, 3 H), 2.65-2.70 (m, 2 H), 2.72-2.81 (m, 2 H), 3.41-3.47 (m, 2 H), 3.80-3.87 (m, 2 H), 4.47 (dd, J = 12.49, 1.26 Hz , 2 H), 7.43-7.47 (m, 2 H), 7.48-7.53 (m, 4 H), 7.64 (s, 2 H), 8.11-8.16 (m, 4 H).
MS ESI / APCI Dual (+): 511.5 [M + H] ⁺ .

Example 46 1- (1-benzoylpiperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine Except that benzoyl chloride is used instead of pivaloyl chloride, Example 45 The reaction was carried out in the same manner to obtain the title compound (67 mg, quant) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.33-1.65 (m, 2 H), 1.66-2.06 (m, 2 H), 2.42-3.13 (m, 7 H), 3.32-3.58 (m, 2 H ), 3.70-3.99 (m, 3 H), 4.62-4.89 (m, 1 H), 7.34-7.56 (m, 11 H), 7.65 (s, 2 H), 8.10-8.19 (m, 4 H).
MS ESI / APCI Dual (+): 531.3 [M + H] ⁺ , 553.2 [M + Na] ⁺ .
Example 47 1- [1- (2,5-Dimethyl-3-furoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine Instead of pivaloyl chloride The reaction was carried out substantially in the same manner as in Example 45 except that dimethylfuran-3-carbonyl chloride was used to obtain the title compound (69 mg, quant) as a colorless amorphous.
MS ESI / APCI Dual (+): 549.3 [M + H] ⁺ , 571.2 [M + Na] ⁺ .
Example 48 Substantially except that cyclohexanecarbonyl chloride is used instead of 1- [1- (cyclohexylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine pivaloyl chloride. The reaction was carried out in the same manner as in Example 45 to obtain the title compound (69 mg, quant) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.12-2.03 (m, 13 H), 2.24-2.79 (m, 8 H), 2.89-3.12 (m, 1 H), 3.36-3.55 (m, 2 H ), 3.74-4.10 (m, 3 H), 4.59-4.77 (m, 1 H), 7.40-7.56 (m, 6 H), 7.65 (s, 2 H), 8.10-8.19 (m, 4 H).
MS ESI / APCI Dual (+): 537.3 [M + H] ⁺ , 559.3 [M + Na] ⁺ .

Example 49 Isobutyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate Substantially except that isobutyl chloroformate was used instead of pivaloyl chloride The reaction was carried out in the same manner as in Example 45 to obtain the title compound (59 mg, 0.112 mmol, quant.) As a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 0.92 (d, J = 6.683 Hz, 6 H), 1.33-1.53 (m, 2 H), 1.71-2.00 (m, 3 H), 2.40-2.58 (m , 3 H), 2.61-2.86 (m, 4 H), 3.39-3.50 (m, 2 H), 3.76-3.92 (m, 4 H), 4.10-4.31 (m, 2 H), 7.42-7.55 (m , 6 H), 7.62-7.67 (m, 2 H), 8.10-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 527.3 [M + H] ⁺ , 549.3 [M + Na] ⁺ .
Example 50 1- [1- (cyclobutylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine Substantially except that cyclobutanecarbonyl chloride is used instead of pivaloyl chloride The reaction was carried out in the same manner as in Example 45 to obtain the title compound (119 mg, quant) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.30-1.43 (m, 2 H), 1.78-1.88 (m, 3 H), 1.90-1.99 (m, 1 H), 2.08-2.18 (m, 2 H ), 2.28-2.38 (m, 2 H), 2.45-2.60 (m, 4 H), 2.63-2.71 (m, 2 H), 2.88-2.95 (m, 1 H), 3.19-3.29 (m, 1 H ), 3.40-3.49 (m, 2 H), 3.71-3.79 (m, 1 H), 3.79-3.89 (m, 2 H), 4.60-4.67 (m, 1 H), 7.43-7.48 (m, 2 H ), 7.49-7.53 (m, 4 H), 7.64 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 509.5 [M + H] ⁺ .

Example 51 Using 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-methylbutanoyl) piperidin-4-yl] piperazine pivaloyl chloride instead of 2-methylbutyryl chloride The reaction was carried out substantially in the same manner as in Example 45, except that the title compound (106 mg, 0.208 mmol, 89%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 0.84-0.91 (m, 3 H), 1.05-1.12 (m, 3 H), 1.32-1.46 (m, 3 H), 1.64-1.73 (m, 1 H ), 1.81-1.93 (m, 2 H), 2.46-2.64 (m, 5 H), 2.65-2.71 (m, 2 H), 2.96-3.07 (m, 1 H), 3.40-3.50 (m, 2 H ), 3.79-3.89 (m, 2 H), 3.97-4.05 (m, 1 H), 4.66-4.76 (m, 1 H), 7.44-7.48 (m, 2 H), 7.48-7.54 (m, 4 H ), 7.65 (s, 2 H), 8.13-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 511.5 [M + H] ⁺ .
Example 52 Ethyl 5- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -5-oxopentanoate instead of pivaloyl chloride The reaction was carried out substantially in the same manner as in Example 45 except that ryl chloride was used to obtain the title compound (115 mg, 0.202 mmol, 86%) as a colorless amorphous.
MS ESI / APCI Dual (+): 569.5 [M + H] ⁺ .

Example 53 1- (2,6-Diphenylisonicotinoyl) -4- {1-[(4-methoxycyclohexyl) carbonyl] -4-yl} piperazine (cis-trans mixture)
Oxalyl chloride (1.02 ml) was added to a suspension of 4-methoxycyclohexanecarboxylic acid (cis / trans mixture) (1.0 g, 6.32 mmol) in toluene (3.0 ml), and the mixture was stirred at 80 ° C. for 2 hours. The solvent was distilled off under reduced pressure to obtain 4-methoxycyclohexanecarboxylic acid chloride (1.07 g, 6.06 mmol). A chloroform (amylene-containing) suspension of 4-methoxycyclohexanecarboxylic acid chloride obtained by the above operation was converted into 1-[(2,6-dichloroisonicotinoyl) -4-piperidin-4-yl) piperazine (2.56). g, 6.0 mmol) and triethylamine (1.26 ml, 9.0 mmol) in chloroform (containing amylene) (30 ml), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (cis / trans mixture: 3.36 g, 5.92 mmol).
Example 54 1- (2,6-Diphenylisonicotinoyl) -4- {1-[(4-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazine (trans form)
The cis-trans mixture (300 mg) obtained in Example 53 was purified by preparative TLC (10% methanol / chloroform) to obtain the title compound (178 mg) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.15-1.25 (m, 2 H), 1.34-1.47 (m, 2 H), 1.53-1.64 (m, 2 H), 1.76-1.82 (m, 2 H ), 1.83-1.94 (m, 2 H), 2.13-2.18 (m, 2 H), 2.45 (tt, J = 11.72, 3.41Hz, 1 H), 2.49-2.58 (m, 4 H), 2.66-2.73 (m, 2 H), 3.00-3.07 (m, 1 H), 3.16 (tt, J = 10.72, 4.13, 4.01 Hz, 1 H), 3.36 (s, 3 H), 3.43-3.49 (m, 2 H ), 3.81-3.90 (m, 2 H), 3.94-4.00 (m, 1 H), 4.65-4.71 (m, 1 H), 7.45-7.49 (m, 2 H), 7.50-7.55 (m, 4 H ), 7.66 (s, 2 H), 8.14-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 567.5 [M + H] ⁺ .
Example 55 1-acetyl-4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperazine (1) 1-acetylpiperazine (1.0 g, 7.80 mmol) in chloroform (40 ml) were added triethylamine (1.30 ml, 9.36 mmol) and 4-nitrophenyl chloroformate (1.89 g, 9.36 mmol), and the mixture was stirred at room temperature for 15 minutes. The reaction solution was poured into water, and the organic layer was washed with saturated brine and dried over magnesium sulfate. Concentration under reduced pressure gave 4-nitrophenyl 4-acetylpiperazine-1-carbamate (2.34 g, quant.) As a colorless solid. Used in the next step without further purification.
(2) N of 1- (2,6-diphenylisonicotinoyl) -4-piperidin-4-ylpiperazine (1.50 g, 3.52 mmol) and diisopropylethylamine (0.735 ml, 4.22 mmol) obtained in Reference Example 4 , N-dimethylformamide (17 ml) was added 4-nitrophenyl 4-acetylpiperazine-1-carbamate (1.17 g, 3.90 mmol) obtained in Example 55 (1), and the mixture was heated to reflux for 3 hours. The reaction mixture was poured into water, and the organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (0-7% methanol / chloroform) to give the title compound (901 mg, 1.15 mmol, 40%) as a colorless amorphous product.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.44-1.53 (m, 2 H), 1.78-1.86 (m, 2 H), 2.11 (s, 3 H), 2.44-2.57 (m, 3 H), 2.66-2.73 (m, 2 H), 2.76-2.83 (m, 2 H), 3.18-3.23 (m, 2 H), 3.23-3.30 (m, 2 H), 3.42-3.50 (m, 4 H), 3.58-3.63 (m, 2 H), 3.75-3.80 (m, 2 H), 3.82-3.89 (m, 2 H), 7.44-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 581.3 [M + H] ⁺ .

Example 56 1- (2,6-Diphenylisonicotinoyl) -4- [1- (piperidin-1-ylcarbonyl) piperidin-4-yl] piperazine 1-piperidinecarbonyl chloride instead of pivaloyl chloride The reaction was carried out substantially in the same manner as in Example 45, except that the title compound (101 mg, 0.188 mmol, 80%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.44-1.61 (m, 6 H), 1.77-1.83 (m, 2 H), 2.42-2.49 (m, 1 H), 2.50-2.55 (m, 2 H ), 2.67-2.77 (m, 4 H), 3.15-3.20 (m, 4 H), 3.42-3.48 (m, 2 H), 3.69-3.74 (m, 2 H), 3.82-3.87 (m, 2 H ), 7.44-7.48 (m, 4 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 538.3 [M + H] ⁺ .

Example 57 4-Iodobenzoic acid chloride is used in place of 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-iodobenzoyl) piperidin-4-yl] piperazine pivaloyl chloride The reaction was carried out substantially in the same manner as in Example 45, except that the title compound (2.30 g, 3.5 mmol, 99%) was obtained as a pale yellow amorphous.
MS ESI / APCI Dual (+): 657.1 [M + H] ⁺ .
Example 58 1- (2,6-Diphenylisonicotinoyl) -4- [1- (4-pyridin-3-ylbenzoyl) piperidin-4-yl] piperazine 1 obtained in Example 56 under argon atmosphere -(2,6-diphenylisonicotinoyl) -4- [1- (4-iodobenzoyl) piperidin-4-yl] piperazine (100 mg, 0.152 mmol), pyridine-3-boronic acid (28 mg, 0.23 mmol), A suspension of bis (triphenylphosphine) palladium (II) dichloride (2 mg, 0.003 mmol), 1M aqueous sodium carbonate solution (0.46 ml, 0.46 mmol) in acetonitrile / ethanol (2: 1, 3 ml) under microwave irradiation. Stir at 20 ° C. for 20 minutes. The reaction solution was filtered through celite, and the filtrate was extracted with chloroform. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (73 mg, 0.12 mmol, 79%) as a colorless amorphous.
MS ESI / APCI Dual (+): 608.3 [M + H] ⁺ .
Example 59 1- (2,6-Diphenylisonicotinoyl) -4- [1- (4-pyridin-4-ylbenzoyl) piperidin-4-yl] piperazine Pyridine-4 instead of pyridine-3-boronic acid The reaction was carried out in substantially the same manner as in Example 58 except that boronic acid was used to obtain the title compound (66 mg, 0.109 mmol, 71%).
MS ESI / APCI Dual (+): 608.3 [M + H] ⁺ .

Example 60 1- (2,6-Diphenylisonicotinoyl) -4- [1- (piperidin-4-ylcarbonyl) piperidin-4-yl] piperazine tert-Butyl 4-({ 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1-carboxylate (13.76 g, 21.57 mmol) in methanol (86 ml) 4M hydrochloric acid-ethyl acetate solution (43 ml) was added, and the mixture was stirred overnight at room temperature. After evaporating the solvent under reduced pressure, the residue was made alkaline by adding a saturated aqueous sodium hydrogen carbonate solution, extracted with chloroform, and the resulting organic layer was dried over anhydrous magnesium sulfate. After concentration, purification by NH-type silica gel column chromatography (methanol / chloroform) gave the title compound (10.78 g, 20.07 mmol, 93%).
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.47 (m, 2 H), 1.61-1.75 (m, 4 H), 1.80-1.93 (m, 2 H), 2.45-2.73 (m, 9 H ), 2.97-3.07 (m, 1 H), 3.10-3.17 (m, 2 H), 3.41-3.49 (m, 2 H), 3.78-3.90 (m, 2 H), 3.93-4.02 (m, 1 H ), 4.62-4.72 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 538.3 [M + H] ⁺ .

Example 61 1- {1-[(1-Benzoylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
1- (2,6-diphenylisonicotinoyl) -4- [1- (piperidin-4-ylcarbonyl) piperidin-4-yl] piperazine (100 mg, 0.186 mmol), triethylamine (0.032 ml, 0.279 mmol) in chloroform Benzoyl chloride (0.032 ml, 0.279 mmol) was added to the (amylene-containing) (2 ml) solution, and the mixture was stirred at room temperature for 1 hour. After completion of the reaction, 1M aqueous sodium hydroxide solution was added to make the reaction solution alkaline. The organic layer was washed with water and saturated brine, and then dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (111 mg, 0.173 mmol, 93%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.49 (m, 2 H), 1.57-1.67 (m, 1 H), 1.75-1.97 (m, 5 H), 2.46-2.62 (m, 4 H ), 2.65-2.73 (m, 2 H), 2.73-2.82 (m, 1 H), 2.83-3.12 (m, 3 H), 3.40-3.50 (m, 2 H), 3.76-3.92 (m, 3 H ), 3.93-4.01 (m, 1 H), 4.62-4.76 (m, 2 H), 7.37-7.42 (m, 5 H), 7.44-7.49 (m, 2 H), 7.49-7.55 (m, 4 H ), 7.65 (s, 2 H), 8.13-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 642.3 [M + H] ⁺ , 664.4 [M + Na] ⁺ .
Example 62 1- (2,6-Diphenylisonicotinoyl) -4- {1-[(1-propionylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine benzoyl chloride instead of propionyl chloride The reaction was carried out substantially in the same manner as in Example 61 except that: The title compound (90 mg, 0.152 mmol, 82%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.14 (t, J = 7.57 Hz, 3 H), 1.33-1.49 (m, 2 H), 1.55-1.99 (m, 6 H), 2.26-2.42 (m , 2 H), 2.45-2.62 (m, 4 H), 2.62-2.76 (m, 4 H), 2.98-3.13 (m, 2 H), 3.39-3.51 (m, 2 H), 3.78-4.03 (m , 4 H), 4.54-4.70 (m, 2 H), 7.43-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.10-8.19 (m, 4 H).
MS ESI / APCI Dual (+): 594.2 [M + H] ⁺ .
Example 63 1- (2,6-diphenylisonicotinoyl) -4- (1-{[1- (methoxyacetyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazine benzoyl chloride instead of methoxy The reaction was carried out in substantially the same manner as in Example 61 except that acetyl chloride was used to obtain the title compound (101 mg, 0.166 mmol, 89%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.62-1.98 (m, 6 H), 2.45-2.63 (m, 4 H), 2.64-2.79 (m, 4 H ), 3.00-3.12 (m, 2 H), 3.42 (s, 3 H), 3.43-3.48 (m, 2 H), 3.80-3.89 (m, 2 H), 3.91-4.00 (m, 2 H), 4.04-4.16 (m, 2 H), 4.48-4.58 (m, 1 H), 4.60-4.70 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.55 (m, 4 H), 7.62-7.67 (m, 2 H), 8.11-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 610.4 [M + H] ⁺ , 632.3 [M + Na] ⁺ .

Example 64 Methyl 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-carboxylate instead of benzoyl chloride The reaction was carried out substantially in the same manner as in Example 61 except that methyl was used to obtain the title compound (155 mg, 0.260 mmol, 93%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.48 (m, 2 H), 1.62-1.80 (m, 4 H), 1.81-1.95 (m, 2 H), 2.45-2.73 (m, 7 H ), 2.75-2.91 (m, 2 H), 2.99-3.10 (m, 1 H), 3.41-3.49 (m, 2 H), 3.69 (s, 3 H), 3.78-3.90 (m, 2 H), 3.91-3.99 (m, 1 H), 4.04-4.31 (m, 2 H), 4.60-4.71 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.16 (m, 4 H).
MS ESI / APCI Dual (+): 596.2 [M + H] ⁺ , 618.3 [M + Na] ⁺ .
Example 65 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl)-N, N-dimethylpiperidine-1-carboxamidobenzoyl chloride The reaction was carried out substantially in the same manner as in Example 61 except that N, N-dimethylaminocarbonyl chloride was used instead to obtain the title compound (160 mg, 0.263 mmol, 94%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.49 (m, 2 H), 1.65-1.73 (m, 2 H), 1.74-1.96 (m, 4 H), 2.46-2.79 (m, 9 H ), 2.82 (s, 6 H), 3.00-3.09 (m, 1 H), 3.40-3.50 (m, 2 H), 3.61-3.73 (m, 2 H), 3.78-3.91 (m, 2 H), 3.92-4.02 (m, 1 H), 4.62-4.72 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13- 8.16 (m, 4 H).
MS ESI / APCI Dual (+): 609.3 [M + H] ⁺ , 631.1 [M + Na] ⁺ .

Example 66 1- (2,6-Diphenylisonicotinoyl) -4- (1-{[1- (methylsulfonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazine benzoyl chloride instead of methane The reaction was carried out substantially in the same manner as in Example 61 except for using sulfonyl chloride to obtain the title compound (169 mg, 0.274 mmol, 98%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.75-1.97 (m, 6 H), 2.45-2.73 (m, 7 H), 2.79 (s, 3 H), 2.83-2.92 (m, 2 H), 3.01-3.11 (m, 1 H), 3.40-3.50 (m, 2 H), 3.71-3.79 (m, 2 H), 3.80-3.97 (m, 3 H), 4.60-4.70 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.63-7.66 (m, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 616.3 [M + H] ⁺ .
Example 67 Isopropyl 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1-carboxylate benzoyl chloride instead of isopropylchloro The reaction was carried out substantially in the same manner as in Example 61 except that formate was used to obtain the title compound (165 mg, 0.265 mmol, 95%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.23 (d, J = 6.41 Hz, 6 H), 1.34-1.48 (m, 2 H), 1.56-1.78 (m, 4 H), 1.80-1.95 (m , 2 H), 2.46-2.72 (m, 7 H), 2.73-2.85 (m, 2 H), 2.99-3.10 (m, 1 H), 3.40-3.49 (m, 2 H), 3.79-3.90 (m , 2 H), 3.92-4.01 (m, 1 H), 4.08-4.29 (m, 2 H), 4.62-4.70 (m, 1 H), 4.86-4.95 (m, 1 H), 7.44-7.48 (m , 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 624.3 [M + H] ⁺ , 646.3 [M + Na] ⁺ .
Example 68 Ethyl 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1-carboxylate benzoyl chloride instead of ethyl chloro The reaction was carried out substantially in the same manner as in Example 61 except that formate was used to obtain the title compound (153 mg, 0.251 mmol, 90%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.25 (t, J = 7.10 Hz, 3 H), 1.34-1.47 (m, 2 H), 1.54-1.80 (m, 4 H), 1.81-1.96 (m , 2 H), 2.46-2.60 (m, 4 H), 2.60-2.73 (m, 3 H), 2.74-2.90 (m, 2 H), 3.00-3.10 (m, 1 H), 3.39-3.51 (m , 2 H), 3.80-3.90 (m, 2 H), 3.92-4.01 (m, 1 H), 4.08-4.29 (m, 4 H), 4.62-4.71 (m, 1 H), 7.44-7.49 (m , 2 H), 7.49-7.55 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 610.3 [M + H] ⁺ , 632.3 [M + Na] ⁺ .

Example 69 4-{[4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] carbonyl} morpholine benzoyl The reaction was carried out substantially in the same manner as in Example 61 except that 4-morpholinylcarbonyl chloride was used instead of chloride to obtain the title compound (172 mg, 0.264 mmol, 95%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.65-1.95 (m, 6 H), 2.46-2.72 (m, 7 H), 2.75-2.85 (m, 2 H ), 2.99-3.10 (m, 1 H), 3.21-3.29 (m, 4 H), 3.40-3.49 (m, 2 H), 3.63-3.69 (m, 4 H), 3.69-3.75 (m, 2 H ), 3.79-3.90 (m, 2 H), 3.91-4.00 (m, 1 H), 4.61-4.70 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H ), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 651.3 [M + H] ⁺ , 673.2 [M + Na] ⁺ .
Example 70 Ethyl [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] (oxo) acetate benzoyl chloride The reaction was carried out substantially in the same manner as in Example 61 except that ethyl oxalyl chloride was used instead of to give the title compound (162 mg, 0.254 mmol, 91%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.32-1.49 (m, 5 H), 1.71-1.82 (m, 3 H), 1.83-1.96 (m, 3 H), 2.45-2.62 (m, 4 H ), 2.64-2.73 (m, 2 H), 2.74-2.82 (m, 1 H), 2.85-2.94 (m, 1 H), 3.02-3.11 (m, 1 H), 3.12-3.21 (m, 1 H ), 3.39-3.50 (m, 2 H), 3.71-3.79 (m, 1 H), 3.80-3.89 (m, 2 H), 3.90-3.98 (m, 1 H), 4.28-4.37 (m, 2 H ), 4.38-4.46 (m, 1 H), 4.61-4.69 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 638.3 [M + H] ⁺ , 660.3 [M + Na] ⁺ .

Example 71 1- (2,6-diphenylisonicotinoyl) -4- (1-{[1- (pyridin-2-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazinebenzoyl chloride The reaction was carried out substantially in the same manner as in Example 61 except that 2-pyridylcarbonyl chloride was used instead of to give the title compound (158 mg, 0.246 mmol, 88%) as a colorless amorphous.
MS ESI / APCI Dual (+): 643.4 [M + H] ⁺ , 665.2 [M + Na] ⁺ .
Example 72 N, N '-[(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) di-4,1-phenylene] 1- (1-benzoylpiperidin-4-yl) -4- (2,6-dichloroisonicotinoyl) piperazine (45 mg, 0.100 mmol), 4-acetamidophenyl obtained in Reference Example 10 under a diacetamide argon atmosphere Boronic acid (54 mg, 0.300 mmol), tetrakistriphenylphosphine palladium (0) (12 mg, 0.010 mmol), sodium carbonate (70 mg, 0.66 mmol) in ethanol / dimethoxyethane / water (3: 2: 1, 1.5 ml) The suspension was stirred at 150 ° C. for 20 minutes under microwave irradiation. Chloroform was added to the reaction solution, and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by preparative TLC (chloroform / acetone / methanol) to obtain the title compound (64 mg, quant.) As a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.36-1.66 (m, 2 H), 1.70-2.06 (m, 2 H), 2.11-2.30 (m, 6 H), 2.43-3.13 (m, 7 H ), 3.35-3.52 (m, 2 H), 3.72-3.95 (m, 3 H), 4.58-4.92 (m, 1 H), 7.35-7.43 (m, 5 H), 7.49-7.54 (m, 2 H ), 7.55-7.65 (m, 4 H), 7.73-7.82 (m, 2 H), 7.99-8.09 (m, 4 H).
MS ESI / APCI Dual (+): 645.4 [M + H] ⁺ .

Reaction substantially similar to Example 72 was implemented using the corresponding reagent, and the compound of Example 73-104 and Example 535-539 was synthesize | combined.
Example 73 4,4 '-(4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) diphenol
MS ESI / APCI Dual (+): 563.4 [M + H] ⁺ .
Example 74 1- (1-Benzoylpiperidin-4-yl) -4- [2,6-bis (4-methoxyphenyl) isonicotinoyl] piperazine
¹ H-NMR (300 MHz, CDCl ₃ ) δ1.35-2.06 (m, 4 H), 2.45-2.63 (m, 3 H), 2.64-3.11 (m, 4 H), 3.38-3.52 (m, 2 H), 3.75-3.96 (m, 9 H), 4.61-4.90 (m, 1 H), 6.98-7.06 (m, 4 H), 7.35-7.43 (m, 5 H), 7.51 (s, 2 H) , 8.05-8.13 (m, 4 H)
MS ESI / APCI Dual (+): 591.4 [M + H] ⁺ .
Example 75 1- (1-Benzoylpiperidin-4-yl) -4- [2,6-bis (3-methoxyphenyl) isonicotinoyl] piperazine
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.36-1.69 (m, 2 H), 1.69-2.03 (m, 2 H), 2.45-2.63 (m, 3 H), 2.64-3.10 (m, 4 H ), 3.37-3.51 (m, 2 H), 3.78-3.88 (m, 3 H), 3.91 (s, 6 H), 4.65-4.89 (m, 1 H), 6.98-7.03 (m, 2 H), 7.35-7.46 (m, 7 H), 7.63 (s, 2 H), 7.66-7.76 (m, 4 H)
MS ESI / APCI Dual (+): 591.5 [M + H] ⁺ .

Example 76 1,1 ′-[(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) di-3,1-phenylene] Diethanon
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.36-1.68 (m, 2 H), 1.69-2.08 (m, 2 H), 2.48-2.65 (m, 3 H), 2.66-3.15 (m, 10 H ), 3.38-3.56 (m, 2 H), 3.73-3.99 (m, 3 H), 4.58-4.91 (m, 1 H), 7.33-7.45 (m, 5 H), 7.58-7.68 (m, 2 H ), 7.76 (s, 2 H), 8.01-8.10 (m, 2 H), 8.35-8.45 (m, 2 H), 8.66-8.74 (m, 2 H)
MS ESI / APCI Dual (+): 615.4 [M + H] ⁺ .
Example 77 1,1 ′-[(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) di-4,1-phenylene] Diethanon
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.36-1.68 (m, 2 H), 1.70-2.07 (m, 2 H), 2.43-3.13 (m, 13 H), 3.36-3.60 (m, 2 H ), 3.72-3.99 (m, 3 H), 4.63-4.88 (m, 1 H), 7.35-7.44 (m, 5 H), 7.76 (s, 2 H), 8.07-8.15 (m, 4 H), 8.21-8.28 (m, 4 H)
MS ESI / APCI Dual (+): 615.4 [M + H] ⁺ .
Example 78 N, N '-[(4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) di-3,1-phenylene] Diacetamide
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.35-2.03 (m, 4 H), 2.11-2.30 (m, 6 H), 2.43-3.11 (m, 7 H), 3.34-3.52 (m, 2 H ), 3.65-3.96 (m, 3 H), 4.59-4.91 (m, 1 H), 7.33-7.46 (m, 7 H), 7.59 (s, 2 H), 7.63-7.83 (m, 6 H), 8.16-8.25 (m, 2 H)
MS ESI / APCI Dual (+): 645.5 [M + H] ⁺ .
Example 79 5,5 ′-(4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) dipyrimidine
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.36-1.68 (m, 2 H), 1.71-2.17 (m, 2 H), 2.51-2.67 (m, 3 H), 2.67-3.14 (m, 4 H ), 3.37-3.55 (m, 2 H), 3.74-3.97 (m, 3 H), 4.60-4.92 (m, 1 H), 7.34-7.45 (m, 5 H), 7.79 (s, 2 H), 9.34 (s, 2 H), 9.44 (s, 4 H).
MS ESI / APCI Dual (+): 535.5 [M + H] ⁺ .

Example 80 1- (1-Benzoylpiperidin-4-yl) -4- {2,6-bis [4- (trifluoromethoxy) phenyl] isonicotinoyl} piperazine
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.44-1.67 (m, 2 H), 1.68-2.03 (m, 2 H), 2.47-2.65 (m, 3 H), 2.65-3.12 (m, 4 H ), 3.39-3.53 (m, 2 H), 3.76-3.95 (m, 3 H), 4.64-4.89 (m, 1 H), 7.31-7.43 (m, 9 H), 7.64 (s, 2 H), 8.12-8.20 (m, 4 H)
MS ESI / APCI Dual (+): 699.4 [M + H] ⁺ .
Example 81 3,3 ′-(4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) diphenol
¹ H-NMR (600 MHz, DMSO-d ₆ ) δ 1.18-1.93 (m, 4 H), 2.40-2.67 (m, 5 H), 2.69-3.13 (m, 2 H), 3.22-3.38 (m, 2 H), 3.47-3.80 (m, 3 H), 4.31-4.64 (m, 1 H), 6.83-6.92 (m, 2 H), 7.26-7.46 (m, 7 H), 7.56-7.71 (m, 4 H), 7.77 (s, 2 H), 9.63 (s, 2 H).
MS ESI / APCI Dual (+): 563.5 [M + H] ⁺ .
Example 82 4,4 ′-(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) dibenzamide
¹ H-NMR (600 MHz, DMSO-d ₆ ) δ 1.30-1.47 (m, 2 H), 1.63-1.78 (m, 1 H), 1.78-1.93 (m, 1 H), 2.44-2.68 (m, 5 H), 2.70-2.83 (m, 1 H), 2.94-3.09 (m, 1 H), 3.30-3.38 (m, 2 H), 3.52-3.76 (m, 3 H), 4.39-4.57 (m, 1 H), 7.33-7.51 (m, 7 H), 8.02-8.06 (m, 6 H), 8.10 (s, 2 H), 8.33-8.38 (m, 4 H).
MS ESI / APCI Dual (+): 617.5 [M + H] ⁺ .
Example 83 3,3 '-(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) dibenzamide
¹ H-NMR (600 MHz, DMSO-d ₆ ) δ 1.29-1.47 (m, 2 H), 1.62-1.77 (m, 1 H), 1.78-1.93 (m, 1 H), 2.43-2.68 (m, 5 H), 2.70-2.84 (m, 1 H), 2.92-3.12 (m, 1 H), 3.29-3.39 (m, 2 H), 3.52-3.81 (m, 3 H), 4.39-4.57 (m, 1 H), 7.34-7.38 (m, 2 H), 7.39-7.46 (m, 3 H), 7.48-7.56 (m, 2 H), 7.62-7.69 (m, 2 H), 7.97-8.02 (m, 2 H), 8.05 (s, 2 H), 8.14-8.24 (m, 2 H), 8.43-8.51 (m, 2 H), 8.64-8.69 (m, 2 H).
MS ESI / APCI Dual (−): 615.5 [MH] ^- .

Example 84 1- (1-Benzoylpiperidin-4-yl) -4- [2,6-bis (2-fluorophenyl) isonicotinoyl] piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.39-1.51 (m, 1 H), 1.52-1.65 (m, 1 H), 1.73-1.86 (m, 1 H), 1.90-2.02 (m, 1 H ), 2.53-2.62 (m, 3 H), 2.66-2.73 (m, 2 H), 2.75-2.87 (m, 1 H), 2.94-3.10 (m, 1 H), 3.46-3.56 (m, 2 H ), 3.77-3.91 (m, 3 H), 4.71-4.83 (m, 1 H), 7.16-7.21 (m, 2 H), 7.28-7.32 (m, 2 H), 7.37-7.45 (m, 7 H ), 7.77-7.80 (m, 2 H), 8.11-8.19 (m, 2 H).
MS ESI / APCI Dual (+): 567.4 [M + H] ⁺ .
Example 85 1- (1-Benzoylpiperidin-4-yl) -4- [2,6-bis (2-methylphenyl) isonicotinoyl] piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.64 (m, 2 H), 1.70-1.83 (m, 1 H), 1.86-2.01 (m, 1 H), 2.44 (s, 6 H), 2.50-2.61 (m, 3 H), 2.62-2.70 (m, 2 H), 2.72-2.88 (m, 1 H), 2.93-3.10 (m, 1 H), 3.43-3.55 (m, 2 H), 3.72-3.93 (m, 3 H), 4.65-4.84 (m, 1 H) 7.26-7.33 (m, 6 H), 7.35 (s, 2 H), 7.36-7.43 (m, 5 H), 7.44-7.47 (m, 2 H).
MS ESI / APCI Dual (+): 559.5 [M + H] ⁺ .
Example 86 4,4 '-(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) bis (N, N-dimethylaniline)
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.36-1.66 (m, 2 H), 1.70-1.84 (m, 1 H), 1.86-2.02 (m, 1 H), 2.46-2.60 (m, 3 H ), 2.63-2.73 (m, 2 H), 2.73-2.85 (m, 1 H), 2.94-3.09 (m, 13 H), 3.41-3.49 (m, 2 H), 3.73-3.89 (m, 3 H ), 4.65-4.86 (m, 1 H), 6.77-6.84 (m, 4 H), 7.34-7.44 (m, 7 H), 8.02-8.09 (m, 4 H).
MS ESI / APCI Dual (+): 617.5 [M + H] ⁺ .

Example 87 2,2 '-(4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} pyridine-2,6-diyl) diphenol
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.35-1.70 (m, 2 H), 1.71-2.00 (m, 2 H), 2.48-2.65 (m, 3 H), 2.66-2.87 (m, 3 H), 2.89-3.11 (m, 1 H), 3.42-3.53 (m, 2 H), 3.77-3.92 (m, 3 H), 4.67-4.86 (m, 1 H), 6.97-7.07 (m, 4 H), 7.33-7.44 (m, 7 H), 7.67-7.71 (m, 4 H).
MS ESI / APCI Dual (+): 563.4 [M + H] ⁺ .
Example 88 1- (1-Benzoylpiperidin-4-yl) -4- [2,6-bis (4-methylphenyl) isonicotinoyl] piperazine
MS ESI / APCI Dual (+): 559.4 [M + H] ⁺ .
Example 89 1- (1-Benzoylpiperidin-4-yl) -4- [2,6-bis (3-methylphenyl) isonicotinoyl] piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.37-1.65 (m, 2 H), 1.69-1.85 (m, 1 H), 1.86-2.03 (m, 1 H), 2.47 (s, 6 H) , 2.49-2.62 (m, 3 H), 2.65-2.73 (m, 2 H), 2.74-2.87 (m, 1 H), 2.92-3.08 (m, 1 H), 3.39-3.51 (m, 2 H) , 3.75-3.94 (m, 3 H), 4.68-4.85 (m, 1 H), 7.26-7.29 (m, 2 H), 7.36-7.44 (m, 7 H), 7.62 (s, 2 H), 7.90 -7.93 (m, 2 H), 7.94-7.98 (m, 2 H).
MS ESI / APCI Dual (+): 559.4 [M + H] ⁺ .

Example 90 1- (1-Benzoylpiperidin-4-yl) -4- {2,6-bis [4- (trifluoromethylphenyl] isonicotinoyl} piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.37-1.64 (m, 2 H), 1.70-1.85 (m, 1 H), 1.87-2.03 (m, 1 H), 2.50-2.63 (m, 3 H), 2.67-2.87 (m, 3 H), 2.94-3.11 (m, 1 H), 3.43-3.51 (m, 2 H), 3.77-3.93 (m, 3 H), 4.70-4.86 (m, 1 H), 7.36-7.45 (m, 5 H), 7.75 (s, 2 H), 7.76-7.82 (m, 4 H), 8.23-8.27 (m, 4 H).
MS ESI / APCI Dual (+): 667.4 [M + H] ⁺ .
Example 91 1- (1-Benzoylpiperidin-4-yl) -4- {2,6-bis [3- (trifluoromethylphenyl] isonicotinoyl} piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.37-1.65 (m, 2 H), 1.71-1.86 (m, 1 H), 1.87-2.02 (m, 1 H), 2.48-2.65 (m, 3 H), 2.68-2.87 (m, 3 H), 2.93-3.11 (m, 1 H), 3.41-3.51 (m, 2 H), 3.76-3.96 (m, 3 H), 4.66-4.87 (m, 1 H), 7.36-7.44 (m, 5 H), 7.65-7.69 (m, 2 H), 7.72-7.76 (m, 4 H), 8.32-8.39 (m, 4 H).
MS ESI / APCI Dual (+): 667.4 [M + H] ⁺ .
Example 92 4 ′-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -4,2 ′: 6 ′, 4 ″ -terpyridine
MS ESI / APCI Dual (+): 533.4 [M + H] ⁺ .
Example 93 N, N '-({4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2, 6-diyl} di-4,1-phenylene) diacetate
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.35-1.48 (m, 2 H), 1.55-1.76 (m, 3 H), 1.77-1.97 (m, 3 H), 2.07-2.12 (m, 3 H), 2.19-2.26 (m, 6 H), 2.47-2.62 (m, 4 H), 2.63-2.78 (m, 4 H), 3.02-3.14 (m, 2 H), 3.38-3.49 (m, 2 H), 3.74-3.92 (m, 3 H), 3.93-4.01 (m, 1 H), 4.53-4.71 (m, 2 H), 7.52 (s, 2 H), 7.57-7.64 (m, 4 H) , 7.69-7.80 (m, 2 H), 8.00-8.09 (m, 4 H).
MS ESI / APCI Dual (+): 694.5 [M + H] ⁺ .

Example 94 N, N '-({4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2, 6-Diyl} di-3,1-phenylene) diacetate
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.31-1.47 (m, 2 H), 1.56-1.75 (m, 3 H), 1.76-1.96 (m, 3 H), 2.06-2.12 (m, 3 H), 2.16-2.27 (m, 6 H), 2.44-2.61 (m, 4 H), 2.62-2.77 (m, 4 H), 2.99-3.16 (m, 2 H), 3.36-3.47 (m, 2 H), 3.76-3.90 (m, 3 H), 3.91-4.01 (m, 1 H), 4.52-4.60 (m, 1 H), 4.61-4.70 (m, 1 H), 7.35-7.44 (m, 2 H), 7.57 (s, 2 H), 7.65-7.71 (m, 2 H), 7.71-7.79 (m, 2 H), 7.82-7.94 (m, 2 H), 8.16-8.28 (m, 2 H) .
MS ESI / APCI Dual (+): 716.6 [M + Na] ⁺ .
Example 95 N, N '-({4-[(4- {1-[(4-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6-diyl} Di-4,1-phenylene) diacetamide
MS ESI / APCI Dual (+): 681.8 [M + H] ⁺ .
Example 96 N, N '-({4-[(4- {1-[(4-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6-diyl} Di-3,1-phenylene) diacetamide
MS ESI / APCI Dual (+): 681.5 [M + H] ⁺ .
Example 97 4,4 ′-{4-[(4- {1-[(4-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6-diphenol
MS ESI / APCI Dual (+): 599.5 [M + H] ⁺ .
Example 98 4,4 '-{4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6 -Diphenol
MS ESI / APCI Dual (+): 612.6 [M + H] ⁺ .

Example 99 4,4 ′-{4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6 -Diyl} Dibenzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.13-1.39 (m, 3 H), 1.42-1.54 (m, 1 H), 1.55-1.65 (m, 2 H), 1.72-1.85 (m, 2 H), 1.97 (s, 3 H), 2.44-2.67 (m, 8 H), 2.83-2.92 (m, 1 H), 2.95-3.12 (m, 2 H), 3.30-3.41 (m, 1 H) , 3.62-3.83 (m, 3 H), 3.97-4.06 (m, 1 H), 4.29-4.43 (m, 2 H), 7.45-7.52 (m, 2 H), 8.01-8.06 (m, 6 H) , 8.09-8.14 (m, 2 H), 8.33-8.38 (m, 4 H).
MS ESI / APCI Dual (+): 666.6 [M + H] ⁺ .
Example 100 3,3 ′-{4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6 -Diyl} Dibenzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.13-1.38 (m, 3 H), 1.41-1.52 (m, 1 H), 1.54-1.64 (m, 2 H), 1.71-1.85 (m, 2 H), 1.97 (s, 3 H), 2.42-2.68 (m, 8 H), 2.82-2.91 (m, 1 H), 2.94-3.11 (m, 2 H), 3.26-3.46 (m, 1 H) , 3.62-3.82 (m, 3 H), 3.96-4.06 (m, 1 H), 4.29-4.43 (m, 2 H), 7.49-7.56 (m, 2 H), 7.62-7.69 (m, 2 H) , 7.97-8.02 (m, 2 H), 8.05 (s, 2 H), 8.16-8.24 (m, 2 H), 8.44-8.50 (m, 2 H), 8.64-8.70 (m, 2 H).
MS ESI / APCI Dual (+): 666.3 [M + H] ⁺ .
Example 101 5,5 '-{4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6 -Diyl} bis (1H-indole)
MS ESI / APCI Dual (+): 658.3 [M + H] ⁺ .
Example 102 ({4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] pyridine-2,6-diyl} di -4,1-phenylene) dimethanol
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.59-1.75 (m, 3 H), 1.77-1.96 (m, 5 H), 2.09 (s, 3 H), 2.45-2.62 (m, 4 H), 2.63-2.76 (m, 4 H), 3.00-3.15 (m, 2 H), 3.40-3.50 (m, 2 H), 3.78-4.00 (m, 4 H), 4.51-4.61 (m, 1 H), 4.61-4.69 (m, 1 H), 4.74-4.82 (m, 4 H), 7.48-7.53 (m, 4 H), 7.61-7.64 (m, 2 H), 8.11-8.15 (m, 4 H).
MS ESI / APCI Dual (+): 640.4 [M + H] ⁺ .

Example 103 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- [2,6-bis (3-fluorophenyl) isonicotinoyl] piperazine
MS ESI / APCI Dual (+): 616.2 [M + H] ⁺ .
Example 104 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- [2,6-bis (4-fluorophenyl) isonicotinoyl] piperazine
MS ESI / APCI Dual (+): 616.2 [M + H] ⁺ .
Example 105 4 ′-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2,2 ′: 6 ′, 2 ″ -terpyridine In an argon atmosphere, Reference Example 10 1- (1-benzoylpiperidin-4-yl) -4- (2,6-dichloroisonicotinoyl) piperazine (67 mg, 0.15 mmol), tributyl (2-pyridyl) tin (138 mg, 0.375 mmol) obtained in A suspension of tetrakistriphenylphosphine palladium (0) (12 mg, 0.01 mmol) in toluene (1.0 ml) was stirred at 160 ° C. for 50 minutes under microwave irradiation. After the solvent was distilled off, the obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (80 mg, 0.15 mmol, quant.) As a yellow solid.
MS ESI / APCI Dual (+): 533.5 [M + H] ⁺ .
Example 106 4 ′-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -3,2 ′: 6 ′, 3 ″ -terpyridine tributyl (2-pyridyl) tin Substantially the same reaction as in Example 105 except that 3- (tri-n-butylstannyl) pyridine was used instead of to give the title compound (69 mg, 0.13 mmol, 86%) as a yellow solid. It was.
MS ESI / APCI Dual (+): 533.4 [M + H] ⁺ .

Example 107 4-({4- [1- (3-Fluorobenzoyl) piperidin-4-yl] piperazin-1-yl} carbonyl) -2-phenylquinoline 2-phenyl-4-yl obtained in Reference Example 20 [(4-Piperidin-4-ylpiperazin-1-yl) carbonyl] quinoline (50 mg, 0.125 mmol), 3-fluorobenzoic acid (18 mg, 0.125 mmol), triethylamine (17 μl, 0.125 mmol) in chloroform (containing amylene) (1.0 ml) To the solution was added EDC.HCl (24 mg, 0.125 mmol), and the mixture was stirred at room temperature for 62 hours. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the product was purified by preparative TLC (methanol / chloroform) to obtain the title compound (47 mg, 0.090 mmol, 72%) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.35-1.65 (m, 2 H), 1.68-2.03 (m, 2 H), 2.33-2.64 (m, 3 H), 2.68-3.11 (m, 4 H ), 3.18-3.29 (m, 2 H), 3.67-4.15 (m, 3 H), 4.60-4.84 (m, 1 H), 7.05-7.19 (m, 3 H), 7.32-7.42 (m, 1 H ), 7.45-7.61 (m, 4 H), 7.72-7.84 (m, 3 H), 8.12-8.24 (m, 3 H).
MS ESI / APCI Dual (+): 523.3 [M + H] ⁺ , 545.2 [M + Na] ⁺ .
Example 108 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2-phenylquinoline 2-phenyl-4-[(4-piperidine obtained in Reference Example 20 -4-ylpiperazin-1-yl) carbonyl] quinoline (50 mg, 0.125 mmol) and triethylamine (0.017 ml, 0.125 mmol) in chloroform (containing amylene) (1 ml) were added with benzoyl chloride (0.015 ml, 0.125 mmol) And stirred at room temperature for 1 hour. The reaction mixture was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the product was purified by preparative TLC (methanol / chloroform) to obtain the title compound (64 mg, quant.) As a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.30-2.04 (m, 4 H), 2.33-2.65 (m, 3 H), 2.66-3.11 (m, 4 H), 3.13-3.34 (m, 2 H ), 3.69-4.14 (m, 3 H), 4.61-4.88 (m, 1 H), 7.34-7.43 (m, 5 H), 7.45-7.61 (m, 4 H), 7.73-7.84 (m, 3 H ), 8.12-8.24 (m, 3 H).
MS ESI / APCI Dual (+): 505.3 [M + H] ⁺ , 527.5 [M + Na] ⁺ .

Example 109 4-({4- [1- (2,5-dimethyl-3-furoyl) piperidin-4-yl] piperazin-1-yl} carbonyl) -2-phenylquinolinebenzoyl chloride instead of 2,5 The reaction was carried out in substantially the same manner as in Example 108 except that -dimethyl-3-furoyl chloride was used to obtain the title compound (67 mg, quant) as a colorless amorphous.
MS ESI / APCI Dual (+): 523.3 [M + H] ⁺ , 545.2 [M + Na] ⁺ .
Example 110 4-({4- [1- (Cyclohexylcarbonyl) piperidin-4-yl] piperazin-1-yl} carbonyl) -2-phenylquinoline Substantially except that cyclohexanecarbonyl chloride is used instead of benzoyl chloride The reaction was carried out in the same manner as in Example 108 to obtain the title compound (65 mg, quant) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.10-2.02 (m, 13 H), 2.25-2.61 (m, 6 H), 2.66-2.83 (m, 2 H), 2.91-3.07 (m, 1 H ), 3.18-3.29 (m, 2 H), 3.84-4.12 (m, 3 H), 4.59-4.74 (m, 1 H), 7.43-7.61 (m, 4 H), 7.72-7.84 (m, 3 H ), 8.11-8.25 (m, 3 H).
MS ESI / APCI Dual (+): 511.3 [M + H] ⁺ , 533.3 [M + Na] ⁺ .
Example 111 Isobutyl 4- {4-[(2-phenylquinolin-4-yl) carbonyl] piperazin-1-yl} piperidin-1-carboxylate Substantially except that chloroformate isobutyl ester is used instead of benzoyl chloride The reaction was carried out in the same manner as in Example 108 to obtain the title compound (64 mg, quant) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 0.92 (d, J = 6.68 Hz, 6 H), 1.32-1.51 (m, 2 H), 1.71-1.83 (m, 2 H), 1.84-1.99 (m , 1 H), 2.32-2.54 (m, 3 H), 2.64-2.85 (m, 4 H), 3.16-3.28 (m, 2 H), 3.84 (d, J = 6.68 Hz, 2 H), 3.86- 4.08 (m, 2 H), 4.09-4.29 (m, 2 H), 7.44-7.61 (m, 4 H), 7.71-7.84 (m, 3 H), 8.12-8.24 (m, 3 H).
MS ESI / APCI Dual (+): 501.2 [M + H] ⁺ , 523.3 [M + Na] ⁺ .

Example 112 4-({4- [1- (morpholin-4-ylcarbonyl) piperidin-4-yl] piperazin-1-yl} carbonyl) -2-phenylquinolinebenzoyl chloride instead of 4-morpholinylcarbonyl The reaction was carried out in substantially the same manner as in Example 108 except that chloride was used to obtain the title compound (42 mg, 61%) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.39-1.55 (m, 2 H), 1.76-1.86 (m, 2 H), 2.44 (s, 3 H), 2.70-2.84 (m, 4 H), 3.25 (t, J = 4.82 Hz, 4 H), 3.68 (dd, J = 4.97, 4.35 Hz, 4 H), 3.71-3.81 (m, 2 H), 3.86-4.08 (m, 2 H), 7.46- 7.62 (m, 6 H), 7.74-7.84 (m, 3 H), 8.14-8.25 (m, 3 H).
MS ESI / APCI Dual (+): 514.3 [M + H] ⁺ , 536 [M + Na] ⁺ .
Example 113 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (4-fluorophenyl) quinoline 4-methyl compound obtained in Reference Example 9 under an argon atmosphere {[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2-chloroquinoline (46 mg, 0.100 mmol), 4-fluorophenylboronic acid (21 mg, 0.150 mmol), tetrakistriphenyl A suspension of phosphine palladium (0) (12 mg, 0.010 mmol), sodium carbonate (35 mg, 0.33 mmol) in ethanol / dimethoxyethane / water (3: 2: 1, 1.5 ml) was stirred at 150 ° C. under microwave irradiation for 20 ° C. Stir for minutes. The reaction solution was extracted with chloroform, and the organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by NH silica gel column chromatography (ethyl acetate / hexane) to give the title compound (49 mg, 0.094 mmol, 94%) as a colorless amorphous product.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.37-1.49 (m, 1 H), 1.49-1.66 (m, 1 H), 1.70-1.83 (m, 1 H), 1.86-1.98 (m, 1 H ), 2.37-2.50 (m, 2 H), 2.51-2.62 (m, 1 H), 2.69-2.84 (m, 3 H), 2.93-3.06 (m, 1 H), 3.18-3.29 (m, 2 H ), 3.77-3.86 (m, 1 H), 3.87-3.96 (m, 1 H), 3.98-4.08 (m, 1 H), 4.69-4.82 (m, 1 H), 7.22 (t, J = 8.48 Hz , 2 H), 7.36-7.44 (m, 5 H), 7.58 (t, J = 7.34 Hz, 1 H), 7.73-7.82 (m, 3 H), 8.13-8.21 (m, 3 H).
MS ESI / APCI Dual (+): 523.4 [M + H] ⁺ .

Example 114 3- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl)] benzonitrile obtained in Reference Example 9 under an argon atmosphere 4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2-chloroquinoline (46 mg, 0.100 mmol), 3-cyanophenylboronic acid (22 mg, 0.150 mmol), tris (Dibenzylideneacetone) dipalladium (0) (9 mg, 0.010 mmol), tri-tert-butylphosphine (4 mg, 0.020 mmol), cesium carbonate (107 mg, 0.33 mmol) in THF (2 ml) under microwave irradiation Stir at 150 ° C. for 20 minutes. The reaction solution was filtered through celite, and the filtrate was extracted with chloroform. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by NH silica gel column chromatography (ethyl acetate / hexane) to give the title compound (28 mg, 0.0529 mmol, 55%) as a colorless amorphous product.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.36-1.48 (m, 1 H), 1.49-1.66 (m, 1 H), 1.71-1.85 (m, 1 H), 1.86-1.99 (m, 1 H ), 2.38-2.50 (m, 2 H), 2.52-2.62 (m, 1 H), 2.71-2.82 (m, 3 H), 2.93-3.06 (m, 1 H), 3.18-3.27 (m, 2 H ), 3.77-3.87 (m, 1 H), 3.89-3.97 (m, 1 H), 3.98-4.07 (m, 1 H), 4.69-4.81 (m, 1 H), 7.34-7.43 (m, 5 H ), 7.60-7.67 (m, 2 H), 7.74-7.79 (m, 2 H), 7.79-7.85 (m, 2 H), 8.19-8.24 (m, 1 H), 8.37-8.42 (m, 1 H ), 8.51-8.54 (m, 1 H).
MS ESI / APCI Dual (+): 530.5 [M + H] ⁺ .

Reactions substantially similar to Example 113 or 114 were carried out using the corresponding reagents to synthesize the compounds of Examples 115-136 and Examples 540-541.
Example 115 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (4-methoxyphenyl) quinoline
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.34-1.65 (m, 2 H), 1.67-2.04 (m, 2 H), 2.32-2.64 (m, 3 H), 2.66-3.11 (m, 4 H ), 3.15-3.31 (m, 2 H), 3.71-4.10 (m, 6 H), 4.62-4.88 (m, 1 H), 7.01-7.09 (m, 2 H), 7.33-7.43 (m, 5 H ), 7.49-7.57 (m, 1 H), 7.69-7.81 (m, 3 H), 8.08-8.22 (m, 3 H).
MS ESI / APCI Dual (+): 535.5 [M + H] ⁺ .
Example 116 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (3-methoxyphenyl) quinoline
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.34-1.66 (m, 2 H) 1.68-2.03 (m, 2 H) 2.31-2.65 (m, 3 H) 2.67-3.11 (m, 4 H) 3.16- 3.28 (m, 2 H) 3.70-4.10 (m, 6 H) 4.61-4.87 (m, 1 H) 7.00-7.07 (m, 1 H) 7.33-7.49 (m, 6 H) 7.53-7.62 (m, 1 H) 7.65-7.84 (m, 5 H) 8.17-8.25 (m, 1 H)
MS ESI / APCI Dual (+): 535.4 [M + H] ⁺ .
Example 117 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (4-hydroxyphenyl) quinoline
¹ H-NMR (300 MHz, CDCl3) δ 1.18-2.06 (m, 4 H), 2.32-2.66 (m, 3 H), 2.68-3.10 (m, 4 H), 3.12-3.35 (m, 2 H) , 3.68-4.09 (m, 3 H), 4.60-4.88 (m, 1 H), 6.84-6.95 (m, 2 H), 7.32-7.44 (m, 5 H), 7.48-7.57 (m, 1 H) , 7.63-7.80 (m, 3 H), 7.92-8.03 (m, 2 H), 8.11-8.20 (m, 1 H).
MS ESI / APCI Dual (+): 521.4 [M + H] ⁺ .

Example 118 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (3-hydroxyphenyl) quinoline
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.34-1.68 (m, 2 H), 1.69-2.01 (m, 2 H), 2.31-2.64 (m, 3 H), 2.68-3.09 (m, 4 H ), 3.15-3.27 (m, 2 H), 3.72-4.11 (m, 3 H), 4.59-4.89 (m, 1 H), 6.88-6.95 (m, 1 H), 7.30-7.43 (m, 6 H ), 7.51-7.66 (m, 3 H), 7.70 (s, 1 H), 7.72-7.82 (m, 2 H), 8.16-8.23 (m, 1 H).
MS ESI / APCI Dual (+): 521.4 [M + H] ⁺ .
Example 119 N- [4- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) phenyl] acetamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.36-1.64 (m, 2 H), 1.69-2.01 (m, 2 H), 2.20 (s, 3 H), 2.37-2.49 (m, 2 H), 2.51-2.61 (m, 1 H), 2.69-2.85 (m, 3 H), 2.92-3.06 (m, 1 H), 3.17-3.28 (m, 2 H), 3.75-3.87 (m, 1 H), 3.88-4.07 (m, 2 H), 4.67-4.82 (m, 1 H), 7.35-7.42 (m, 5 H), 7.45-7.49 (m, 1 H), 7.53-7.57 (m, 1 H), 7.63-7.70 (m, 2 H), 7.72-7.81 (m, 3 H), 8.10-8.15 (m, 2 H), 8.15-8.19 (m, 1 H).
MS ESI / APCI Dual (+): 562.4 [M + H] ⁺ .
Example 120 N- [3- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) phenyl] acetamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.36-1.64 (m, 2 H), 1.69-2.01 (m, 2 H), 2.20 (s, 3 H), 2.37-2.49 (m, 2 H), 2.51-2.61 (m, 1 H), 2.69-2.85 (m, 3 H), 2.92-3.06 (m, 1 H), 3.17-3.28 (m, 2 H), 3.75-3.87 (m, 1 H), 3.88-4.07 (m, 2 H), 4.67-4.82 (m, 1 H), 7.35-7.42 (m, 5 H), 7.45-7.49 (m, 1 H), 7.53-7.57 (m, 1 H), 7.63-7.70 (m, 2 H), 7.72-7.81 (m, 3 H), 8.10-8.15 (m, 2 H), 8.15-8.19 (m, 1 H).
MS ESI / APCI Dual (+): 562.4 [M + H] ⁺ .

Example 121 4- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) benzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.64 (m, 2 H), 1.69-1.98 (m, 2 H), 2.37-2.50 (m, 2 H), 2.52-2.61 (m, 1 H ), 2.68-2.85 (m, 3 H), 2.93-3.08 (m, 1 H), 3.18-3.29 (m, 2 H), 3.76-3.86 (m, 1 H), 3.87-3.96 (m, 1 H ), 3.99-4.08 (m, 1 H), 4.65-4.85 (m, 1 H), 5.56-5.75 (m, 1 H), 6.12-6.28 (m, 1 H), 7.35-7.44 (m, 5 H ), 7.58-7.63 (m, 1 H), 7.77-7.84 (m, 3 H), 7.95-8.00 (m, 2 H), 8.20-8.24 (m, 1 H), 8.24-8.29 (m, 2 H ).
MS ESI / APCI Dual (+): 548.5 [M + H] ⁺ .
Example 122 3- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) benzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.64 (m, 2 H), 1.69-1.98 (m, 2 H), 2.37-2.50 (m, 2 H), 2.52-2.61 (m, 1 H), 2.68-2.85 (m, 3 H), 2.93-3.08 (m, 1 H), 3.18-3.29 (m, 2 H), 3.76-3.86 (m, 1 H), 3.87-3.96 (m, 1 H), 3.99-4.08 (m, 1 H), 4.65-4.85 (m, 1 H), 5.56-5.75 (m, 1 H), 6.12-6.28 (m, 1 H), 7.35-7.44 (m, 5 H), 7.58-7.63 (m, 1 H), 7.77-7.84 (m, 3 H), 7.95-8.00 (m, 2 H), 8.20-8.24 (m, 1 H), 8.24-8.29 (m, 2 H).
MS ESI / APCI Dual (+): 548.4 [M + H] ⁺ .
Example 123 1- [3- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) phenyl] ethanone
MS ESI / APCI Dual (+): 547.4 [M + H] ⁺ .
Example 124 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- [4- (methylsulfonyl) phenyl] quinoline
MS ESI / APCI Dual (+): 583.4 [M + H] ⁺ .
Example 125 N- [4- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) phenyl] methanesulfonamide
MS ESI / APCI Dual (+): 598.4 [M + H] ⁺ .

Example 126 4- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) benzonitrile
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.64 (m, 2 H), 1.69-1.84 (m, 1 H), 1.84-2.01 (m, 1 H), 2.36-2.50 (m, 2 H ), 2.52-2.62 (m, 1 H), 2.68-2.86 (m, 3 H), 2.90-3.09 (m, 1 H), 3.15-3.27 (m, 2 H), 3.75-3.95 (m, 2 H ), 4.00-4.09 (m, 1 H), 4.67-4.82 (m, 1 H), 7.35-7.43 (m, 5 H), 7.60-7.65 (m, 1 H), 7.78-7.85 (m, 5 H ), 8.20-8.24 (m, 1 H), 8.27-8.31 (m, 2 H).
MS ESI / APCI Dual (+): 530.3 [M + H] ⁺ .
Example 127 4- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl)-N, N-dimethylbenzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.66 (m, 2 H), 1.69-1.85 (m, 1 H), 1.86-2.00 (m, 1 H), 2.37-2.50 (m, 2 H ), 2.51-2.61 (m, 1 H), 2.68-2.85 (m, 3 H), 2.94-3.08 (m, 4 H), 3.15 (s, 3 H), 3.19-3.28 (m, 2 H), 3.75-3.86 (m, 1 H), 3.88-3.97 (m, 1 H), 3.97-4.08 (m, 1 H), 4.65-4.86 (m, 1 H), 7.35-7.44 (m, 5 H), 7.56-7.63 (m, 3 H), 7.75-7.84 (m, 3 H), 8.17-8.24 (m, 3 H).
MS ESI / APCI Dual (+): 576.4 [M + H] ⁺ .
Example 128 N- [3- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) phenyl] methanesulfonamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.65 (m, 2 H), 1.69-1.84 (m, 1 H), 1.85-2.00 (m, 1 H), 2.35-2.50 (m, 2 H ), 2.52-2.62 (m, 1 H), 2.68-2.87 (m, 3 H), 2.91-3.09 (m, 4 H), 3.16-3.28 (m, 2 H), 3.74-3.87 (m, 1 H ), 3.88-3.97 (m, 1 H), 3.97-4.08 (m, 1 H), 4.64-4.84 (m, 1 H), 6.85-6.91 (m, 1 H), 7.34-7.44 (m, 6 H ), 7.48-7.54 (m, 1 H), 7.56-7.61 (m, 1 H), 7.74-7.84 (m, 3 H), 7.91-7.96 (m, 1 H), 7.99-8.02 (m, 1 H ), 8.16-8.21 (m, 1 H).
MS ESI / APCI Dual (+): 620.4 [M + H] ⁺ .

Example 129 1- [4- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) phenyl] ethanone
MS ESI / APCI Dual (+): 547.5 [M + H] ⁺ .
Example 130 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] quinolin-2-yl} phenol
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.47 (m, 2 H), 1.48-1.77 (m, 3 H), 1.78-1.97 (m, 3 H), 2.10 (s, 3 H), 2.36-2.47 (m, 2 H), 2.51-2.62 (m, 2 H), 2.65-2.79 (m, 4 H), 3.01-3.15 (m, 2 H), 3.16-3.29 (m, 2 H), 3.84-4.02 (m, 4 H), 4.54-4.69 (m, 2 H), 6.93-6.99 (m, 2 H), 7.51-7.56 (m, 1 H), 7.68-7.79 (m, 3 H), 7.99-8.07 (m, 2 H), 8.13-8.19 (m, 1 H).
MS ESI / APCI Dual (+): 570.5 [M + H] ⁺ .
Example 131 4- {4-[(4- {1-[(4-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] quinolin-2-yl} phenol
MS ESI / APCI Dual (+): 557.5 [M + H] ⁺ .
Example 132 4- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} quinolin-2-yl) -N-methylbenzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.64 (m, 2 H), 1.67-2.01 (m, 2 H), 2.36-2.50 (m, 2 H), 2.52-2.61 (m, 1 H ), 2.69-2.86 (m, 3 H), 2.91-3.10 (m, 4 H), 3.17-3.28 (m, 2 H), 3.75-3.87 (m, 1 H), 3.87-3.97 (m, 1 H ), 3.98-4.07 (m, 1 H), 4.63-4.83 (m, 1 H), 6.20-6.28 (m, 1 H), 7.34-7.43 (m, 5 H), 7.57-7.62 (m, 1 H ), 7.76-7.84 (m, 3 H), 7.89-7.94 (m, 2 H), 8.18-8.26 (m, 3 H).
MS ESI / APCI Dual (+): 562.5 [M + H] ⁺ .
Example 133 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (4-methylphenyl) quinoline
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.67 (m, 2 H), 1.69-2.00 (m, 2 H), 2.34-2.49 (m, 5 H), 2.51-2.62 (m, 1 H ), 2.67-2.88 (m, 3 H), 2.89-3.09 (m, 1 H), 3.15-3.30 (m, 2 H), 3.74-3.96 (m, 2 H), 3.97-4.07 (m, 1 H ), 4.65-4.85 (m, 1 H), 7.31-7.43 (m, 7 H), 7.52-7.58 (m, 1 H), 7.72-7.81 (m, 3 H), 8.03-8.09 (m, 2 H ), 8.16-8.21 (m, 1 H).
MS ESI / APCI Dual (+): 519.5 [M + H] ⁺ .

Example 134 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (3-methylphenyl) quinoline
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-2.01 (m, 4 H), 2.30-2.64 (m, 6 H), 2.69-2.90 (m, 3 H), 2.92-3.09 (m, 1 H ), 3.16-3.33 (m, 2 H), 3.71-3.97 (m, 2 H), 3.98-4.08 (m, 1 H), 4.65-4.87 (m, 1 H), 7.28-7.33 (m, 2 H ), 7.35-7.48 (m, 5 H), 7.53-7.61 (m, 1 H), 7.72-7.85 (m, 3 H), 7.89-7.96 (m, 1 H), 7.98-8.05 (m, 1 H ), 8.17-8.27 (m, 1 H).
519.5 [M + H] ⁺ .
Example 135 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (4-fluorophenyl) quinoline
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.99 (m, 4 H), 2.36-2.51 (m, 2 H), 2.52-2.62 (m, 1 H), 2.67-2.88 (m, 3 H ), 2.91-3.10 (m, 1 H), 3.15-3.32 (m, 2 H), 3.74-3.97 (m, 2 H), 3.98-4.07 (m, 1 H), 4.66-4.84 (m, 1 H ), 7.15-7.21 (m, 1 H), 7.34-7.44 (m, 5 H), 7.46-7.54 (m, 1 H), 7.56-7.62 (m, 1 H), 7.74-7.83 (m, 3 H ), 7.89-7.95 (m, 2 H), 8.18-8.23 (m, 1 H).
MS ESI / APCI Dual (+): 523.5 [M + H] ⁺ .
Example 136 4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -2- (4-bromophenyl) quinoline
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.60 (m, 2 H), 1.67-1.81 (m, 1 H), 1.85-1.98 (m, 1 H), 2.35-2.49 (m, 2 H ), 2.51-2.60 (m, 1 H), 2.68-2.85 (m, 3 H), 2.92-3.06 (m, 1 H), 3.17-3.27 (m, 2 H), 3.75-3.86 (m, 1 H ), 3.86-3.94 (m, 1 H), 3.98-4.07 (m, 1 H), 4.67-4.81 (m, 1 H), 7.34-7.43 (m, 5 H), 7.56-7.60 (m, 1 H ), 7.640- 7.68 (m, 2 H), 7.74-7.82 (m, 3 H), 8.03-8.07 (m, 2 H), 8.17-8.21 (m, 1 H).
MS ESI / APCI Dual (+): 583.3 [M + H] ⁺ .

Example 137 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) morpholine 4-[(4- Piperazin-1-ylpiperidin-1-yl) carbonyl] morpholine (38 mg, 0.134 mmol), 2,6-diphenylisonicotinic acid (37 mg, 0.134 mmol), triethylamine (14 μl, 0.134 mmol) in chloroform (containing amylene) ( To the 1.0 ml) solution, EDC · HCl (26 mg, 0.134 mmol) was added and stirred at room temperature for 3 days. The reaction mixture was poured into 3M aqueous sodium hydroxide solution and extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by preparative TLC (10% methanol / chloroform) to obtain the title compound (75 mg, quant.) As a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.41-1.65 (m, 4 H), 1.77-1.87 (m, 2 H), 2.42-2.57 (m, 3 H), 2.65-2.84 (m, 4 H ), 3.25 (t, J = 4.66 Hz, 2 H), 3.41-3.50 (m, 2 H), 3.68 (dd, J = 5.13, 4.51 Hz, 4 H), 3.72-3.81 (m, 2 H), 3.82-3.89 (m, 2 H), 7.43-7.57 (m, 6 H), 7.66 (s, 2 H), 8.13-8.19 (m, 4 H).
MS ESI / APCI Dual (+): 540.3 [M + H] ⁺ , 562.3 [M + Na] ⁺ .
Example 138 4-[(4- {4- [2,6-bis (4-chlorophenyl) isonicotinoyl] piperazin-1-yl} piperidin-1-yl) carbonyl] morpholine
Except for using 2,6-bis (4-chlorophenyl) isonicotinic acid (synthesized by the method described in Journal of Medicinal chemistry, 1972, 15, 809.) instead of 2,6-diphenylisonicotinic acid, Substantially the same reaction as in Example 137 was performed to give the title compound (35 mg, 43%) as a pale yellow amorphous.
MS ESI / APCI Dual (+): 608.2 [M + H] ⁺ .

Example 139 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazine (cis isomer)
The cis-trans mixture (250 mg) obtained in Example 53 was purified by preparative TLC (10% methanol / chloroform) to obtain the title compound (77 mg) as a colorless amorphous.
MS ESI / APCI Dual (+): 567.4 [M + H] ⁺
Example 140 1- (2,6-diphenylisonicotinoyl) -4- [1-({1-[(4-methylpiperazin-1-yl) carbonyl] piperidin-4-yl} carbonyl) piperidine-4- [Il] piperazine The reaction was carried out in substantially the same manner as in Example 61 except that 4-methyl-1-piperazinecarbonyl chloride hydrochloride was used instead of benzoyl chloride to give the title compound (74 mg, 0.112 mmol, 40%) Was obtained as a colorless amorphous.
MS ESI / APCI Dual (+): 664.4 [M + H] ⁺ .
Example 141 3- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -3-oxopropane -1-all
1- (2,6-diphenylisonicotinoyl) -4- [1- (piperidin-4-ylcarbonyl) piperidin-4-yl] piperazine (150 mg, 0.279 mmol), 3-hydroxypropionic acid (3.6 mol / l in H ₂ O) (120 μl, 0.419 mmol) and HOBt · H ₂ O (57 mg, 0.419 mmol) in chloroform (containing amylene) (3.0 ml) were added EDC · HCl (80 mg, 0.419 mmol) and stirred at room temperature for 18 hours. did. The reaction mixture was washed with 1M aqueous sodium hydroxide solution and saturated brine, and purified by silica gel column chromatography (methanol / chloroform) to give the title compound (100 mg, 59%) as a colorless amorphous product.
MS ESI / APCI Dual (+): 610.4 [M + H] ⁺ .

Example 142 4-({4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidin-1-yl} carbonyl) morpholine 1- (9-anthrylcarbonyl) obtained in Reference Example 32 4-morpholinylcarbonyl chloride (120 mg, 0.80 mmol) was added to a solution of 4-piperidin-4-ylpiperazine (200 mg, 0.535 mmol) and triethylamine (75 μl, 0.54 mmol) in chloroform (containing amylene) (3.0 ml). And stirred at room temperature for 1 hour. The reaction solution was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (265 mg) as a pale yellow amorphous.
^{1 H-NMR (300 MHz,} CDCl 3) δ 1.36 - 1.53 (m, 2 H), 1.74 - 1.85 (m, 2 H), 2.28 - 2.36 (m, 2 H), 2.38 - 2.51 (m, 1 H ), 2.70-2.84 (m, 4 H), 3.04-3.09 (m, 2 H), 3.21-3.27 (m, 4 H), 3.64-3.79 (m, 6 H), 4.10-4.17 (m, 2 H ), 7.46-7.56 (m, 4 H), 7.88-7.95 (m, 2 H), 8.00-8.07 (m, 2 H), 8.48 (s, 1 H).
MS ESI (+): 487.2 [M + H] ⁺ .
Example 143 1- (9-anthrylcarbonyl) -4- (1-benzoylpiperidin-4-yl) piperazine
The reaction was carried out substantially in the same manner as in Example 142 except that benzoyl chloride was used instead of 4-morpholinylcarbonyl chloride to obtain the title compound (64 mg, quant.) As a colorless amorphous.
MS ESI (+): 478.2 [M + H] ⁺ .
Example 144 1- (9-anthrylcarbonyl) -4- [1- (2,5-dimethyl-3-furoyl) piperidin-4-yl] piperazine
The reaction was carried out in substantially the same manner as in Example 142 except that 2,5-dimethyl-3-furoyl chloride was used in place of 4-morpholinylcarbonyl chloride to give the title compound (67 mg, quant.) Was obtained as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.33-1.51 (m, 2 H), 1.77-1.91 (m, 2 H), 2.19-2.26 (m, 4 H), 2.27-2.36 (m, 5 H ), 2.45-2.60 (m, 2 H), 2.66-2.96 (m, 4 H), 3.02-3.10 (m, 2 H), 4.10-4.18 (m, 2 H), 5.88 (s, 1 H), 7.45-7.55 (m, 4 H), 7.87-7.95 (m, 2 H), 7.99-8.06 (m, 2 H), 8.48 (s, 1 H).
MS ESI (+): 496.2 [M + H] ⁺ .

Example 145 1- (9-anthrylcarbonyl) -4- [1- (3-methylbenzoyl) piperidin-4-yl] piperazine obtained in Reference Example 32 To a solution of piperidin-4-ylpiperazine (50 mg, 0.134 mmol) and 3-toluic acid (19 mg, 0.134 mmol) in chloroform (containing amylene) (2.0 ml) was added EDC · HCl (26 mg, 0.134 mmol), and the mixture was stirred at room temperature for 16 Stir for hours. The reaction mixture was washed with water and saturated brine, and purified by preparative TLC (10% methanol / chloroform) to give the title compound (51 mg, 0.104 mmol, 78%) as a colorless amorphous product.
MS ESI (+): 492.2 [M + H] ⁺ .
Reaction substantially similar to Example 142 or 145 was implemented using the corresponding reagent, and the compound of Examples 146-192 was obtained hereafter.

Example 146: 1- (9-anthrylcarbonyl) -4- [1- (2-methylbenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 492.2 [M + H] ⁺ .
Example 147: 1- (9-anthrylcarbonyl) -4- [1- (2-chlorobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 512.1 [M + H] ⁺ .
Example 148: 1- (9-anthrylcarbonyl) -4- {1-[(2-methylphenyl) sulfonyl] piperidin-4-yl} piperazine
MS ESI (+): 528.1 [M + H] ⁺ .

Example 149: 1- (9-anthrylcarbonyl) -4- {1-[(2-chlorophenyl) sulfonyl] piperidin-4-yl} piperazine
MS ESI (+): 548.0 [M + H] ⁺ .
Example 150: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -N, N-diphenylpiperidine-1-carboxamide
MS ESI (+): 569.2 [M + H] ⁺ .
Example 151 1: 1- (9-anthrylcarbonyl) -4- [1- (2-fluorobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 496.2 [M + H] ⁺ .
Example 152: 1- (9-anthrylcarbonyl) -4- [1- (2-methoxybenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 508.2 [M + H] ⁺ .
Example 153: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -N, N-diisopropylpiperidine-1-carboxamide
MS ESI (+): 501.3 [M + H] ⁺ .
Example 154: 1- (9-anthrylcarbonyl) -4- [1- (2-bromobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 556.1 [M + H] ⁺ .
Example 155: 1- (9-anthrylcarbonyl) -4- [1- (4-chlorobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 512.2 [M + H] ⁺ .
Example 156: 1- (9-anthrylcarbonyl) -4- [1- (4-methylbenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 492.2 [M + H] ⁺ .

Example 157: 1- (9-anthrylcarbonyl) -4- [1- (piperidin-1-ylcarbonyl) piperidin-4-yl] piperazine
MS ESI (+): 485.2 [M + H] ⁺ .
Example 158: Isobutyl 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidine-1-carboxylate
MS ESI (+): 474.2 [M + H] ⁺ .
Example 159: 1- (9-anthrylcarbonyl) -4- [1- (4-methoxybenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 508.2 [M + H] ⁺ .
Example 160: Phenyl 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidine-1-carboxylate
MS ESI (+): 494.2 [M + H] ⁺ .
Example 161: 1- (9-anthrylcarbonyl) -4- [1- (isopropylsulfonyl) piperidin-4-yl] piperazine
MS ESI (+): 480.2 [M + H] ⁺ .
Example 162: 1- (9-anthrylcarbonyl) -4- [1- (2-nitrobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 523.3 [M + H] ⁺ .

Example 163: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -N-methyl-N-phenylpiperidine-1-carboxamide
MS ESI (+): 507.2 [M + H] ⁺ .
Example 164: 1- (9-anthrylcarbonyl) -4- [1- (4-chlorobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 512.2 [M + H] ⁺ .
Example 165: 1- (9-anthrylcarbonyl) -4- [1- (2,4-dichlorobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 546.1 [M + H] ⁺ .
Example 166: 1-({4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidin-1-yl} carbonyl) imidazolidin-2-one
MS ESI (+): 486.2 [M + H] ⁺ .
Example 167: 1- (9-anthrylcarbonyl) -4- [1- (2-trifluoromethylbenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 546.1 [M + H] ⁺ .
Example 168: 1- (9-anthrylcarbonyl) -4- {1-[(2-chloropyridin-3-yl) carbonyl] piperidin-4-yl} piperazine
MS ESI (+): 513.2 [M + H] ⁺ .
Example 169: 1- (9-anthrylcarbonyl) -4- [1- (3-cyanomethylbenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 503.2 [M + H] ⁺ .
Example 170: 1- (9-anthrylcarbonyl) -4- [1- (2-thienylacetyl) piperidin-4-yl] piperazine
MS ESI (+): 498.2 [M + H] ⁺ .

Example 171: 1- (9-anthrylcarbonyl) -4- [1- (4-tert-butylbenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 534.2 [M + H] ⁺ .
Example 172: Methyl 2-({4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoate
MS ESI (+): 536.2 [M + H] ⁺ .
Example 173: 1- (1-acetylpiperidin-4-yl) -4- (9-anthrylcarbonyl) piperazine
MS ESI (+): 416.3 [M + H] ⁺ .
Example 174: 1- (9-anthrylcarbonyl) -4- [1- (3-methylbutanoyl) piperidin-4-yl] piperazine
MS ESI (+): 458.3 [M + H] ⁺ .
Example 175: 1- (9-anthrylcarbonyl) -4- [1- (2,2-dimethylpropanoyl) piperidin-4-yl] piperazine
MS ESI (+): 458.3 [M + H] ⁺ .
Example 176: 1- (9-anthrylcarbonyl) -4- [1- (cyclohexylcarbonyl) piperidin-4-yl] piperazine
MS ESI (+): 484.3 [M + H] ⁺ .
Example 177: 1- (9-anthrylcarbonyl) -4- [1- (cyclopentylcarbonyl) piperidin-4-yl] piperazine
MS ESI (+): 470.3 [M + H] ⁺ .
Example 178: ethyl 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidine-1-carboxylate
MS ESI (+): 446.2 [M + H] ⁺ .
Example 179: Benzyl 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] piperidine-1-carboxylate
MS ESI (+): 508.3 [M + H] ⁺ .
Example 180: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -N, N-dimethylpiperidine-1-carboxamide
MS ESI (+): 445.3 [M + H] ⁺ .

Example 181 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -N, N-dibutylpiperidine-1-carboxamide
MS ESI (+): 529.3 [M + H] ⁺ .
Example 182: 1- (9-anthrylcarbonyl) -4- [1- (2-furoyl) piperidin-4-yl] piperazine
MS ESI (+): 468.2 [M + H] ⁺ .
Example 183: 1- (9-anthrylcarbonyl) -4- {1-[(1,3-dimethyl-1H-pyrazol-5-yl) carbonyl] piperidin-4-yl} piperazine
MS ESI (+): 496.3 [M + H] ⁺ .
Example 184: 1- (9-anthrylcarbonyl) -4- [1- (2-naphthoyl) piperidin-4-yl] piperazine
MS ESI (+): 528.3 [M + H] ⁺ .
Example 185: 1- (9-anthrylcarbonyl) -4- [1- (3-methyl-2-furoyl) piperidin-4-yl] piperazine
MS ESI (+): 482.3 [M + H] ⁺ .
Example 186: 1- (9-anthrylcarbonyl) -4- {1-[(1-methyl-1H-pyrrol-2-yl) carbonyl] piperidin-4-yl} piperazine
MS ESI (+): 481.3 [M + H] ⁺ .
Example 187: 1- (9-anthrylcarbonyl) -4- [1- (phenylacetyl) piperidin-4-yl] piperazine
MS ESI (+): 492.3 [M + H] ⁺ .

Example 188: 1- (9-anthrylcarbonyl) -4- [1- (pyridin-2-ylcarbonyl) piperidin-4-yl] piperazine
MS ESI (+): 479.3 [M + H] ⁺ .
Example 189: 1- (9-anthrylcarbonyl) -4- [1- (pyridin-3-ylcarbonyl) piperidin-4-yl] piperazine
MS ESI (+): 479.3 [M + H] ⁺ .
Example 190: 1- (9-anthrylcarbonyl) -4- {1- [4- (trifluoromethyl) benzoyl] piperidin-4-yl} piperazine
MS ESI (+): 546.2 [M + H] ⁺ .
Example 191: 1- (9-anthrylcarbonyl) -4- [1- (3,4,5-trifluorobenzoyl) piperidin-4-yl] piperazine
MS ESI (+): 532.2 [M + H] ⁺ .
Example 192: 1- (9-anthrylcarbonyl) -4- [1- (phenylsulfonyl) piperidin-4-yl] piperazine
MS ESI (+): 514.3 [M + H] ⁺ .
Example 193: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -1- (morpholin-4-ylcarbonyl) azepane
Substantially carried out except that 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] azepane is used instead of 1- (9-anthrylcarbonyl) -4-piperidin-4-ylpiperazine The reaction was carried out in the same manner as in Example 142 to obtain the title compound (54 mg, 0.108 mmol, 78%) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.35-1.51 (m, 2 H), 1.63-1.98 (m, 4 H), 2.23-2.34 (m, 2 H), 2.47-2.57 (m, 1 H ), 2.72-2.84 (m, 2 H), 3.00-3.08 (m, 2 H), 3.08-3.31 (m, 6 H), 3.42-3.57 (m, 2 H), 3.62-3.74 (m, 4 H ), 4.06-4.16 (m, 2 H), 7.45-7.56 (m, 4 H), 7.87-7.95 (m, 2 H), 7.99-8.06 (m, 2 H), 8.48 (s, 1 H).
MS ESI (+): 501.3 [M + H] ⁺ .

Example 194: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -1-benzoylazepane
4- [4- (9-anthrylcarbonyl) piperazin-1-yl] azepane instead of 1- (9-anthrylcarbonyl) -4-piperidin-4-ylpiperazine, 4-morpholinylcarbonyl chloride The reaction was carried out substantially in the same manner as in Example 142 except that benzoyl chloride was used for the title compound to give the title compound (53 mg, 0.108 mmol, 82%) as a colorless amorphous substance.
MS ESI (+): 492.3 [M + H] ⁺ .
Example 195: 4- [4- (9-anthrylcarbonyl) piperazin-1-yl] -1- (phenylsulfonyl) azepane
4- [4- (9-anthrylcarbonyl) piperazin-1-yl] azepane instead of 1- (9-anthrylcarbonyl) -4-piperidin-4-ylpiperazine, 4-morpholinylcarbonyl chloride instead The title compound (54 mg, 0.102 mmol, 76%) was obtained as a light brown amorphous substance by carrying out the reaction substantially in the same manner as in Example 142 except that benzenesulfonyl chloride was used.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.42-1.74 (m, 3 H), 1.81-2.02 (m, 3 H), 2.20-2.30 (m, 2 H), 2.52-2.66 (m, 1 H ), 2.66-2.81 (m, 2 H), 2.99-3.06 (m, 2 H), 3.08-3.23 (m, 2 H), 3.30-3.45 (m, 2 H), 4.06-4.14 (m, 2 H ), 7.46-7.57 (m, 7 H), 7.75-7.81 (m, 2 H), 7.86-7.95 (m, 2 H), 8.00-8.07 (m, 2 H), 8.48 (s, 1 H).
MS ESI (+): 528.3 [M + H] ⁺ .
Example 196: 1- (1-benzoylpiperidin-4-yl) -4- (2-methoxy-6-phenylisonicotinoyl) piperazine
Oxalyl chloride (0.19 ml, 2.18 mmol) was added to a suspension of 2-methoxy-6-phenylisonicotinic acid (100 mg, 0.436 mmol) in toluene (1.0 ml), and the mixture was stirred at 90 ° C. for 3 hours. The solvent was distilled off under reduced pressure to obtain 2-methoxy-6-phenylisonicotinic acid chloride.
A suspension of 2-methoxy-6-phenylisonicotinic acid chloride obtained in the above operation in chloroform (containing amylene) (3.0 ml) was treated with 1- (1-benzoylpiperidin-4-yl) piperazine (119 mg, 0.436). mmol) and triethylamine (0.072 ml, 0.523 mmol) in chloroform (containing amylene) (2.0 ml) and stirred at room temperature for 1 hour. The reaction mixture was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by preparative TLC (methanol / acetone / chloroform) to obtain the title compound (178 mg, 0.367 mmol, 84%) as a colorless amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.37-1.67 (m, 2 H), 1.68-2.05 (m, 2 H), 2.41-3.15 (m, 7 H), 3.33-3.52 (m, 2 H ), 3.70-3.92 (m, 3 H), 4.06 (s, 3 H), 4.61-4.91 (m, 1 H), 6.64 (d, J = 0.93 Hz, 1 H), 7.31 (d, J = 1.09 Hz, 1 H), 7.35-7.52 (m, 8 H), 7.99-8.08 (m, 2 H).
MS ESI (+): 485.4 [M + H] ⁺ , 507.4 [M + Na] ⁺ .

Example 197: 4- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -6-phenylpyridin-2-yl) phenol in Reference Example 37 under argon atmosphere The resulting mixture of 1- (1-benzoylpiperidin-4-yl) -4- (2-chloro-6-phenylisonicotinoyl) piperazine (73 mg, about 0.15 mmol), 4-hydroxyphenylboronic acid (21 mg, 0.12 mmol), tetrakistriphenylphosphine palladium (17 mg, 0.015 mmol), sodium carbonate (70 mg, 0.66 mmol) in ethanol / dimethoxyethane / water (3: 2: 1, 1.5 ml) suspension under microwave irradiation Stir at 150 ° C. for 20 minutes. Chloroform was added to the reaction solution, and the organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The residue was purified by preparative TLC (methanol / chloroform)) to give the title compound (38 mg, 0.07 mmol, 58%) as a colorless amorphous.
MS ESI (+): 547.5 [M + H] ⁺ .
Example 198: 3- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -6-phenylpyridin-2-yl) phenol instead of 4-hydroxyphenylboronic acid The title compound (47 mg, 0.086 mmol, 72%) was obtained as a pale yellow amorphous product substantially in the same manner as in Example 197 except that 3-hydroxyphenylboronic acid was used.
MS ESI (+): 547.5 [M + H] ⁺ .
Example 199: 3- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -6-phenylpyridin-2-yl) propan-1-ol
(1) 3- (4-{[4- (1-Benzoylpiperidin-4-yl) piperazin-1-yl] carbonyl} -6-phenylpyridin-2-yl) prop-2-yn-1-ol argon Under atmosphere, a mixture of 1- (1-benzoylpiperidin-4-yl) -4- (2-chloro-6-phenylisonicotinoyl) piperazine obtained in Reference Example 37 (73 mg, about 0.15 mmol), bis ( Triphenylphosphine) palladium (II) dichloride (10 mg, 0.015 mmol), copper (I) iodide (3 mg, 0.015 mmol), triphenylphosphine (8 mg, 0.030 mmol), propargyl alcohol (13 mg, 0.223 mmol), triethylamine ( 104 μl, 0.075 mmol) of THF (1.5 ml) suspension was stirred at 150 ° C. for 20 minutes under microwave irradiation. Chloroform was added to the reaction mixture, and the mixture was filtered through celite. The filtrate was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. Concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (methanol / chloroform) to give 3- (4-{[4- (1-benzoylpiperidin-4-yl) piperazin-1-yl] Carbonyl} -6-phenylpyridin-2-yl) prop-2-yn-1-ol (17 mg, 0.033 mmol, 22%) was obtained as a yellow oil.
(2) To a solution of the compound (17 mg, 0.033 mmol) obtained in (1) above in ethanol (2.0 ml) was added 10% palladium-activated carbon powder (20 mg), and the system was replaced with hydrogen. Stir overnight. The reaction solution was filtered through celite, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (4 mg, 0.008 mmol, 24%) as a yellow amorphous.
¹ H-NMR (300 MHz, CDCl ₃ ) δ 1.35-1.56 (m, 2 H), 1.69-1.99 (m, 2 H), 2.00-2.15 (m, 2 H), 2.46-2.72 (m, 4 H ), 2.73-3.13 (m, 5 H), 3.33-3.69 (m, 4 H), 3.69-3.93 (m, 4 H), 4.66-4.85 (m, 1 H), 7.08-7.14 (m, 1 H ), 7.35-7.55 (m, 9 H), 7.91-7.99 (m, 2 H).
MS ESI (+): 513.5 [M + H] ⁺ .

Example 200: (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine- 2-Il} phenyl) 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-) obtained in Reference Example 38 under argon acetate atmosphere 6-phenylisonicotinoyl) piperazine mixture (200 mg, about 0.25 mmol), 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) phenylacetic acid (292 mg, 1.12 mmol), bis (Triphenylphosphine) palladium (II) dichloride (26 mg, 0.037 mmol), 1M aqueous sodium carbonate (1.49 ml, 1.49 mmol) in acetonitrile / water (2: 1, 3 ml) suspension at 150 ° C. under microwave irradiation For 20 minutes. Chloroform was added to the reaction mixture, and the mixture was filtered through celite. The filtrate was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (84 mg, 0.13 mmol, 52%) as a brown amorphous.
MS ESI (+): 638.3 [M + H] ⁺ , 660.3 [M + Na] ⁺ .
Reaction substantially similar to Example 200 was implemented using the corresponding reagent, and the compounds of Examples 201-208 and Examples 542-550 were obtained.
Example 201: 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} phenol
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.32-1.47 (m, 2 H), 1.59-1.95 (m, 7 H), 2.10 (s, 3 H), 2.46-2.62 (m, 4 H), 2.64-2.78 (m, 4 H), 3.00-3.15 (m, 2 H), 3.40-3.49 (m, 2 H), 3.78-3.99 (m, 4 H), 4.53-4.69 (m, 2 H), 6.90-6.99 (m, 2 H), 7.39-7.58 (m, 5 H), 7.97-8.03 (m, 2 H), 8.07-8.19 (m, 2 H).
MS ESI / APCI Dual (+): 596.3 [M + H] ⁺ .

Example 202: 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} benzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.49 (m, 2 H), 1.58-1.97 (m, 6 H), 2.09 (s, 3 H), 2.47-2.62 (m, 4 H), 2.63-2.78 (m, 4 H), 2.97-3.17 (m, 2 H), 3.39-3.52 (m, 2 H), 3.79-4.00 (m, 4 H), 4.51-4.70 (m, 2 H), 5.80-5.97 (m, 1 H), 6.30-6.48 (m, 1 H), 7.43-7.56 (m, 3 H), 7.64-7.72 (m, 2 H), 7.96 (m, 2 H), 8.09- 8.16 (m, 2 H), 8.22 (m, 2 H).
MS ESI / APCI Dual (+): 645.4 [M + Na] ⁺ .
Example 203: 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -N-methylbenzamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.48 (m, 2 H), 1.60-1.95 (m, 6 H), 2.09 (s, 3 H), 2.49-2.61 (m, 4 H), 2.65-2.77 (m, 4 H), 3.01-3.16 (m, 5 H), 3.43-3.50 (m, 2 H), 3.81-4.01 (m, 4 H), 4.53-4.70 (m, 2 H), 6.19-6.25 (m, 1 H), 7.45-7.56 (m, 3 H), 7.66-7.71 (m, 2 H), 7.88-7.94 (m, 2 H), 8.10-8.16 (m, 2 H), 8.19-8.25 (m, 2 H).
MS ESI / APCI Dual (+): 637.3 [M + H] ⁺ , 659.4 [M + Na] ⁺ .
Example 204: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1H-Indole
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.63-1.95 (m, 6 H), 2.09 (s, 3 H), 2.47-2.62 (m, 4 H), 2.64-2.77 (m, 4 H), 3.02-3.15 (m, 2 H), 3.44-3.52 (m, 2 H), 3.80-4.01 (m, 4 H), 4.53-4.70 (m, 2 H), 6.66-6.68 (m, 1 H), 7.26-7.28 (m, 1 H), 7.44-7.54 (m, 4 H), 7.59 (s, 1 H), 7.69 (s, 1 H), 8.03-8.07 ( m, 1 H), 8.16-8.20 (m, 2 H), 8.34-8.39 (m, 1 H), 8.40-8.49 (m, 1 H).
MS ESI / APCI Dual (+): 619.3 [M + H] ⁺ , 641.3 [M + Na] ⁺ .
Example 205: (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine- 2-yl} phenyl) methanol MS MS ESI / APCI Dual (+): 610.3 [M + H] ⁺ , 632.2 [M + Na] ⁺ .

Example 206: (3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine- 2-yl} phenyl) methanol
MS ESI / APCI Dual (+): 610.4 [M + H] +.
Example 207: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1H-Indole
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.63-1.96 (m, 6 H), 2.09 (s, 3 H), 2.48-2.61 (m, 4 H), 2.63-2.76 (m, 4 H), 3.02-3.14 (m, 2 H), 3.45-3.51 (m, 2 H), 3.81-4.00 (m, 4 H), 4.52-4.70 (m, 2 H), 6.57-6.63 (m, 1 H), 7.29-7.33 (m, 1 H), 7.44-7.54 (m, 3 H), 7.60 (s, 1 H), 7.69 (s, 1 H), 7.72-7.76 ( m, 1 H), 7.84-7.91 (m, 1 H), 8.14-8.20 (m, 2 H), 8.30 (s, 1 H), 8.47 (br. s., 1 H).
MS ESI / APCI Dual (+): 619.4 [M + H] ⁺ .
Example 208: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1H-indazole
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.36-1.49 (m, 2 H), 1.54-1.77 (m, 3 H), 1.78-1.97 (m, 3 H), 2.10 (s, 3 H), 2.48-2.62 (m, 4 H), 2.66-2.77 (m, 4 H), 3.04-3.15 (m, 2 H), 3.46-3.52 (m, 2 H), 3.81-3.92 (m, 3 H), 3.94-4.01 (m, 1 H), 4.54-4.62 (m, 1 H), 4.63-4.70 (m, 1 H), 7.45-7.57 (m, 3 H), 7.61-7.67 (m, 2 H), 7.72 (s, 1 H), 8.14-8.23 (m, 3 H), 8.25-8.29 (m, 1 H), 8.57 (s, 1 H), 10.23 (br. S., 1 H).
MS ESI / APCI Dual (+): 620.5 [M + H] ⁺ .

Example 209: 2- (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} phenoxy) ethanol (1) In a solution of ethylene glycol mono (4-bromophenyl) ether (1.0 g, 4.6 mmol) in anhydrous tetrahydrofuran (20 ml) at −78 ° C. under an argon atmosphere, 2.66 M n− Butyl lithium hexane solution (4.33 ml, 11.5 mmol) was added dropwise. The reaction solution was brought to −40 ° C. and stirred for 1 hour, and then trimethoxyborane (1.2 g, 11.5 mmol) was added all at once. The reaction mixture was allowed to rise to room temperature, 1M aqueous hydrochloric acid solution (50 ml) was added, and the mixture was stirred for 1 hr, and extracted with ethyl acetate. The aqueous layer was concentrated under reduced pressure, and the obtained solid was washed with chloroform to obtain a crude product (1.0 g) containing [4- (2-hydroxyethoxy) phenyl] boronic acid as a colorless solid. (2) 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6-phenyliso) obtained in Reference Example 37 under an argon atmosphere A mixture of nicotinoyl) piperazine (200 mg, about 0.25 mmol), [4- (2-hydroxyethoxy) phenyl] boronic acid (202 mg, 1.11 mmol), bis (triphenylphosphine) palladium (II) dichloride (26 mg, 0.037 mmol) ) A suspension of 1 M aqueous sodium carbonate (1.11 ml, 1.11 mmol) in acetonitrile / water (2: 1, 4.5 ml) was stirred at 150 ° C. for 20 minutes under microwave irradiation. Chloroform was added to the reaction solution, and the organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (97 mg, 0.15 mmol, 60%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.36-1.48 (m, 2 H), 1.61-1.77 (m, 3 H), 1.79-1.96 (m, 3 H), 2.03-2.13 (m, 4 H ), 2.47-2.62 (m, 4 H), 2.64-2.77 (m, 4 H), 3.03-3.15 (m, 2 H), 3.43-3.49 (m, 2 H), 3.78-3.92 (m, 3 H ), 3.93-4.05 (m, 3 H), 4.16-4.20 (m, 2 H), 4.54-4.62 (m, 1 H), 4.63-4.70 (m, 1 H), 7.04-7.08 (m, 2 H ), 7.45-7.49 (m, 1 H), 7.49-7.54 (m, 2 H), 7.58-7.61 (m, 2 H), 8.11-8.16 (m, 4 H).
MS ESI / APCI Dual (+): 640.4 [M + H] ⁺ .

Example 210: 2- (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} phenyl) ethanol
Substantially carried out except that 4- (2-hydroxyethyl) phenylboronic acid (synthesized by the method described in WO03 / 087061) was used instead of [4- (2-hydroxyethoxy) phenyl] boronic acid. The same reaction as in Example 209 was performed to give the title compound (122 mg, 0.195 mmol, 79%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.52 (m, 3 H), 1.60-1.95 (m, 6 H), 2.09 (s, 3 H), 2.47-2.61 (m, 4 H), 2.63-2.76 (m, 4 H), 2.96 (t, J = 6.65 Hz, 2 H), 3.03-3.14 (m, 2 H), 3.43-3.51 (m, 2 H), 3.81-4.00 (m, 6 H), 4.54-4.69 (m, 2 H), 7.38 (d, J = 8.25 Hz, 2 H), 7.44-7.53 (m, 3 H), 7.61-7.65 (m, 2 H), 8.10 (m, 2 H), 8.12-8.17 (m, 2 H).
MS ESI / APCI Dual (+): 624.5 [M + H] ⁺ , 646.6 [M + Na] ⁺ .
Example 211: N- {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl]- 2-Oxoethyl} acetamide 1- (2,6-diphenylisonicotinoyl) -4- [1- (piperidin-4-ylcarbonyl) piperidin-4-yl] piperazine (100 mg, 0.186 mmol) obtained in Example 60 ), N-acetylglycine (33 mg, 0.279 mmol), and HOBt · H 2 O (38 mg, 0.279 mmol) in chloroform (containing amylene) (2.0 ml) were added EDC · HCI (53 mg, 0.279 mmo) at room temperature overnight. Stir. After completion of the reaction, 1M aqueous sodium hydroxide solution was added to make the reaction solution alkaline. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (104 mg, 0.170 mmol, 88%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.48 (m, 2 H), 1.66-1.83 (m, 4 H), 1.83-1.96 (m, 2 H), 2.05 (s, 3 H), 2.48-2.62 (m, 4 H), 2.65-2.72 (m, 2 H), 2.73-2.86 (m, 2 H), 3.03-3.13 (m, 2 H), 3.42-3.49 (m, 2 H), 3.75-3.89 (m, 3 H), 3.92-3.98 (m, 1 H), 3.98-4.12 (m, 2 H), 4.48-4.55 (m, 1 H), 4.61-4.69 (m, 1 H), 6.58-6.63 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.55 (m, 4 H), 7.65 (s, 2 H), 8.12-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 637.3 [M + H] ⁺ , 659.2 [M + Na] ⁺ .

Example 212 tert-butyl {(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine- 1-yl] -1-methyl-2-oxoethyl} carbamate
The reaction was carried out in substantially the same manner as in Example 211 except that N- (tert-butoxycarbonyl) -L-alanine was used instead of N-acetylglycine, and the title compound (195 mg, 0.275 mmol, 98%) Was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.23-1.33 (m, 3 H), 1.33-1.51 (m, 11 H), 1.56-2.03 (m, 6 H), 2.46-2.63 (m, 4 H ), 2.64-2.84 (m, 4 H), 3.00-3.21 (m, 2 H), 3.41-3.49 (m, 2 H), 3.79-4.02 (m, 4 H), 4.43-4.72 (m, 3 H ), 5.48-5.59 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 709.5 [M + H] ⁺ , 731.5 [M + Na] ⁺ .
Example 213: (2S) -1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -1-oxopropan-2-amine
Instead of tert-butyl-4- (2,6-diphenyl) piperazine-1-carboxylate tert-butyl {(1S) -2- [4-({4- [4- (2,6-diphenylisonicoti Noyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -1-methyl-2-oxoethyl} carbamate was used and the reaction was carried out in substantially the same manner as in Reference Example 2. The title compound (137 mg, 0.225 mmol, 82%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.24 (dd, J = 21.5, 6.87 Hz, 3 H), 1.34-1.48 (m, 2 H), 1.60-1.96 (m, 6 H), 2.45-2.63 (m, 4 H), 2.65-2.81 (m, 4 H), 3.00-3.16 (m, 2 H), 3.40-3.51 (m, 2 H), 3.74-3.99 (m, 5 H), 4.52-4.62 (m, 1 H), 4.62-4.71 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.56 (m, 4 H), 7.65 (s, 2 H), 8.11-8.18 (m , 4 H).
MS ESI / APCI Dual (+): 609.3 [M + H] ⁺ .

Example 214: N-{(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1 -Il] -1-Methyl-2-oxoethyl} acetamide
(2S) -1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1 obtained in Example 213 Acetyl chloride (24 μl, 0.338 mmol) was added to a solution of (-yl) -1-oxopropan-2-amine (130 mg, 0.225 mmol) and triethylamine (47 μl, 0.338 mmol) in chloroform (containing amylene) (3.0 ml) at room temperature. For 10 minutes. The reaction mixture was poured into 1M aqueous sodium hydroxide solution and extracted with chloroform. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by preparative TLC (methanol / chloroform) to obtain the title compound (116 mg, 0.178 mmol, 79%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.27-1.34 (m, 3 H), 1.35-1.49 (m, 2 H), 1.64-1.95 (m, 6 H), 2.00 (d, J = 5.96 Hz , 3 H), 2.46-2.62 (m, 4 H), 2.64-2.72 (m, 2 H), 2.72-2.86 (m, 2 H), 3.01-3.21 (m, 2 H), 3.40-3.51 (m , 2 H), 3.79-3.90 (m, 2 H), 3.90-4.01 (m, 2 H), 4.43-4.59 (m, 1 H), 4.60-4.71 (m, 1 H), 4.81-4.92 (m , 1 H), 6.58-6.68 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.11-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 651.4 [M + H] ⁺ , 673.3 [M + Na] ⁺ .
Example 215: tert-butyl {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -1,1-dimethyl-2-oxoethyl} carbamate
The reaction was carried out in substantially the same manner as in Example 211 except that N- (tert-butoxycarbonyl) -methylalanine was used instead of N-acetylglycine to give the title compound (150 mg, 0.207 mmol, 75%). Obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.31-1.58 (m, 17 H), 1.64-2.00 (m, 6 H), 2.45-2.62 (m, 4 H), 2.64-2.77 (m, 3 H ), 2.81-3.12 (m, 3 H), 3.40-3.53 (m, 2 H), 3.79-3.91 (m, 2 H), 3.92-4.03 (m, 1 H), 4.48-4.72 (m, 3 H ), 4.88-5.14 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.62-7.67 (m, 2 H), 8.11-8.18 (m, 4 H ).
MS ESI / APCI Dual (+): 723.5 [M + H] ⁺ .

Example 216: 1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -2-methyl -1-oxopropan-2-amine
tert-butyl {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazine- instead of tert-butyl-4- (2,6-diphenyl) piperazine-1-carboxylate] 1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -1,1-dimethyl-2-oxoethyl} carbamate was used, and the reaction was carried out in substantially the same manner as in Reference Example 2, The title compound (83 mg, 0.133 mmol, 69%) was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.47 (m, 8 H), 1.58-1.96 (m, 6 H), 2.46-2.62 (m, 4 H), 2.64-2.79 (m, 3 H ), 2.81-2.96 (m, 2 H), 3.01-3.11 (m, 1 H), 3.42-3.50 (m, 2 H), 3.79-3.90 (m, 2 H), 3.93-4.02 (m, 1 H ), 4.62-4.78 (m, 3 H), 7.43-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 623.3 [M + H] ⁺ .
Example 217: N- {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl]- 1,1-dimethyl-2-oxoethyl} acetamide 1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1- obtained in Example 212 Yl} carbonyl) piperidin-1-yl] -2-methyl-1-oxopropan-2-amine (83 mg, 0.133 mmol) and triethylamine (37 μl, 0.266 mmol) in chloroform (containing amylene) in acetic anhydride (3 ml) (0.025 ml, 0.266 mmol) was added and stirred at room temperature for 30 minutes. After completion of the reaction, 1M aqueous sodium hydroxide solution was added to make the reaction solution alkaline. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (70 mg, 0.105 mmol, 80%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.48 (m, 2 H), 1.64 (s, 6 H), 1.69-1.80 (m, 4 H), 1.82-1.95 (m, 2 H) , 1.97 (s, 3 H), 2.46-2.62 (m, 4 H), 2.64-2.80 (m, 3 H), 2.90-3.11 (m, 3 H), 3.40-3.50 (m, 2 H), 3.80 -3.90 (m, 2 H), 3.90-4.00 (m, 1 H), 4.32-4.48 (m, 2 H), 4.60-4.69 (m, 1 H), 6.78 (s, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.11-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 665.3 [M + H] ⁺ , 687.3 [M + Na] ⁺ .

Example 218: tert-butyl [(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine- 1-yl] -1- (hydroxymethyl) -2-oxoethyl] carbamate
The reaction was carried out in substantially the same manner as in Example 211 except that N- (tert-butoxycarbonyl) -L-serine was used instead of N-acetylglycine, and the title compound (115 mg, 0.159 mmol, 57%) Was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.29-1.51 (m, 11 H), 1.64-1.97 (m, 6 H), 2.46-2.63 (m, 4 H), 2.64-2.88 (m, 4 H), 3.00-3.30 (m, 2 H), 3.38-3.49 (m, 2 H), 3.66-3.76 (m, 1 H), 3.76-3.89 (m, 3 H), 3.90-3.99 (m, 1 H), 4.02-4.18 (m, 1 H), 4.40-4.70 (m, 3 H), 5.60-5.71 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.55 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 747.6 [M + Na] ⁺ .
Example 219: (2S) -2-amino-3- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine- 1-yl] -3-oxopropan-1-ol tert-butyl obtained in Example 218 [(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl)] Piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -1- (hydroxymethyl) -2-oxoethyl] carbamate (115 mg, 0.159 mmol) in methanol (6 ml) was added 4N hydrochloric acid- Ethyl acetate solution (3 ml) was added and stirred at room temperature overnight. After evaporating the solvent under reduced pressure, the residue was made alkaline with 1M aqueous sodium hydroxide solution, extracted with chloroform, and the resulting organic layer was dried over anhydrous magnesium sulfate. After concentration, purification by NH silica gel column chromatography (methanol / chloroform) gave the title compound (77 mg, 0.123 mmol, 78%).
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.57-2.07 (m, 7 H), 2.46-2.62 (m, 4 H), 2.64-2.71 (m, 2 H ), 2.72-2.82 (m, 2 H), 3.01-3.20 (m, 2 H), 3.37-3.51 (m, 3 H), 3.58-3.66 (m, 1 H), 3.72-3.78 (m, 1 H ), 3.80-3.90 (m, 2 H), 3.91-4.08 (m, 2 H), 4.48-4.60 (m, 1 H), 4.60-4.71 (m, 1 H), 7.44-7.48 (m, 2 H ), 7.49-7.55 (m, 4 H), 7.65 (s, 2 H), 8.09-8.21 (m, 4 H).
MS ESI / APCI Dual (+): 625.3 [M + H] ⁺ .

Example 220: N-[(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1 -Yl] -1- (hydroxymethyl) -2-oxoethyl] acetamide (2S) -2-amino-3- [4-({4- [4- (2,6-diphenyliso) obtained in Example 219] Nicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -3-oxopropan-1-ol (77 mg, 0.123 mmol) in chloroform (containing amylene) solution (3 ml) anhydrous Acetic acid (0.023 ml, 0.246 mmol) was added and stirred at room temperature for 30 minutes. After completion of the reaction, 1M aqueous sodium hydroxide solution was added to make the reaction solution alkaline. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (53 mg, 0.0795 mmol, 65%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.48 (m, 2 H), 1.68-1.96 (m, 6 H), 2.05 (d, J = 10.54 Hz, 3 H), 2.47-2.62 ( m, 4 H), 2.65-2.72 (m, 2 H), 2.73-2.88 (m, 2 H), 3.02-3.21 (m, 2 H), 3.42-3.49 (m, 2 H), 3.67-3.89 ( m, 5 H), 3.91-3.99 (m, 1 H), 4.04-4.13 (m, 1 H), 4.43-4.57 (m, 1 H), 4.60-4.68 (m, 1 H), 4.88-4.96 ( m, 1 H), 6.77 (d, J = 7.33 Hz, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 667.3 [M + H] ⁺ , 689.2 [M + Na] ⁺ .

Example 221: tert-butyl {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -2-oxoethyl} methylcarbamate
The reaction was carried out substantially in the same manner as in Example 211 except that N- (tert-butoxycarbonyl) -sarcosine was used instead of N-acetylglycine to obtain the title compound (198 mg, quant) as a colorless amorphous substance. .
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.32-1.51 (m, 11 H), 1.55-1.98 (m, 6 H), 2.45-2.62 (m, 4 H), 2.62-2.82 (m, 4 H), 2.91 (s, 3 H), 2.99-3.13 (m, 2 H), 3.38-3.52 (m, 2 H), 3.76-4.06 (m, 5 H), 4.09-4.21 (m, 1 H) , 4.45-4.58 (m, 1 H), 4.59-4.71 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.55 (m, 4 H), 7.65 (s, 2 H), 8.11 -8.17 (m, 4 H).
MS ESI / APCI Dual (+): 709.3 [M + H] ⁺ , 731.1 [M + Na] ⁺ .
Example 222: 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -N-methyl -2-oxoethanamine
tert-butyl [(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] Tert-butyl {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine- instead of -1- (hydroxymethyl) -2-oxoethyl] carbamate 1-yl} carbonyl) piperidin-1-yl] -2-oxoethyl} methylcarbamate was carried out in substantially the same manner as in Example 219 to give the title compound (134 mg, 0.220 mmol, 82%) Was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.34-1.48 (m, 2 H), 1.60-1.96 (m, 6 H), 2.45 (s, 3 H), 2.47-2.63 (m, 4 H) , 2.64-2.79 (m, 4 H), 2.99-3.12 (m, 2 H), 3.38 (s, 2 H), 3.41-3.50 (m, 2 H), 3.77-3.91 (m, 3 H), 3.91 -4.01 (m, 1 H), 4.52-4.61 (m, 1 H), 4.62-4.71 (m, 1 H), 7.44-7.49 (m, 2 H), 7.50-7.55 (m, 4 H), 7.65 (s, 2 H), 8.11-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 609.3 [M + H] ⁺ .

Example 223: N- {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl]- 2-oxoethyl} -N-methylacetamide
(2S) -2-Amino-3- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine- instead of -3-oxopropan-1-ol The reaction was carried out in substantially the same manner as in Example 220 except that 1-yl] -N-methyl-2-oxoethanamine was used to obtain the title compound (116 mg, 0.178 mmol, 85%) as a colorless amorphous product. It was.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.48 (m, 2 H), 1.58-1.96 (m, 6 H), 2.14 (s, 3 H), 2.46-2.63 (m, 4 H), 2.64-2.82 (m, 4 H), 3.00-3.16 (m, 5 H), 3.39-3.50 (m, 2 H), 3.76-3.91 (m, 3 H), 3.91-4.09 (m, 2 H), 4.36-4.45 (m, 1 H), 4.46-4.56 (m, 1 H), 4.60-4.69 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.55 (m, 4 H), 7.63-7.67 (m, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 651.3 [M + H] ⁺ , 673.3 [M + Na] ⁺ .

Example 224: 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl]-N, N -Dimethyl-2-oxoethanamine
The reaction was carried out substantially in the same manner as in Example 211 except that N, N-dimethylglycine was used instead of N-acetylglycine to obtain the title compound (76 mg, 0.119 mmol, 44%) as a colorless amorphous. .
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.49 (m, 2 H), 1.59-1.97 (m, 6 H), 2.29 (s, 6 H), 2.47-2.62 (m, 4 H), 2.63-2.77 (m, 4 H), 3.00-3.19 (m, 4 H), 3.41-3.50 (m, 2 H), 3.78-3.90 (m, 2 H), 3.91-4.01 (m, 1 H), 4.11-4.20 (m, 1 H), 4.51-4.61 (m, 1 H), 4.62-4.70 (m, 1 H), 7.44-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.63-7.66 (m, 2 H), 8.13-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 623.3 [M + H] ⁺ , 645.3 [M + Na] ⁺ .
Example 225: tert-butyl {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -2-oxoethyl} carbamate
The reaction was carried out in substantially the same manner as in Example 211 except that N- (tert-butoxycarbonyl) -glycine was used instead of N-acetylglycine to give the title compound (187 mg, 0.269 mmol, 96%) Obtained as amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.50 (m, 11 H), 1.55-1.96 (m, 6 H), 2.47-2.62 (m, 4 H), 2.65-2.84 (m, 4 H ), 3.00-3.13 (m, 2 H), 3.41-3.50 (m, 2 H), 3.71-3.79 (m, 1 H), 3.81-3.89 (m, 2 H), 3.90-4.02 (m, 3 H ), 4.45-4.56 (m, 1 H), 4.60-4.69 (m, 1 H), 5.47-5.55 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.55 (m, 4 H ), 7.62-7.67 (m, 2 H), 8.11-8.18 (m, 4 H).
MS ESI / APCI Dual (+): 695.3 [M + H] ⁺ , 717.3 [M + Na] ⁺ .

Example 226: 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -2-oxo Ethanamine
tert-butyl [(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] Tert-butyl {2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine- instead of -1- (hydroxymethyl) -2-oxoethyl] carbamate 1-yl} carbonyl) piperidin-1-yl] -2-oxoethyl} carbamate was used substantially in the same manner as in Example 219 to give the title compound (142 mg, 0.239 mmol, 89%). Obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.55-1.96 (m, 6 H), 2.46-2.61 (m, 4 H), 2.64-2.80 (m, 4 H ), 2.98-3.11 (m, 2 H), 3.38-3.51 (m, 4 H), 3.73-3.80 (m, 1 H), 3.80-3.90 (m, 2 H), 3.91-4.00 (m, 1 H ), 4.51-4.60 (m, 1 H), 4.61-4.69 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.63-7.67 (m, 2 H ), 8.11-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 595.3 [M + H] ⁺ , 617.3 [M + Na] ⁺ .
Example 227: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1-carboxamide
1- (2,6-diphenylisonicotinoyl) -4- [1- (piperidin-4-ylcarbonyl) piperidin-4-yl] piperazine (100 mg, 0.186 mmol) acetic acid / water obtained in Example 60 To a solution (2.0 ml) of sodium / tetrahydrofuran (2: 1: 1) was added an aqueous solution (3.0 ml) of sodium cyanate (121 mg, 1.86 mmol), and the mixture was stirred at room temperature for 1 hour and then at 100 ° C. for 2 hours. After completion of the reaction, a saturated aqueous sodium hydrogen carbonate solution was added to make it alkaline. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration, the product was purified by preparative TLC (methanol / chloroform) to obtain the title compound (20 mg, 0.034 mmol, 19%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.47 (m, 2 H), 1.67-1.96 (m, 6 H), 2.47-2.61 (m, 4 H), 2.62-2.72 (m, 3 H ), 2.87-2.94 (m, 2 H), 3.02-3.10 (m, 1 H), 3.42-3.48 (m, 2 H), 3.81-3.88 (m, 2 H), 3.91-4.00 (m, 3 H ), 4.39-4.44 (m, 2 H), 4.62-4.69 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.53 (m, 4 H), 7.63-7.66 (m, 2 H ), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 581.3 [M + H] ⁺ , 603.4 [M + Na] ⁺ .

Example 228: 2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -2-oxo ethanol
The reaction was carried out substantially in the same manner as in Example 211 except that glycolic acid was used in place of N-acetylglycine to obtain the title compound (108 mg, 0.181 mmol, 65%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.48 (m, 2 H), 1.57-1.97 (m, 6 H), 2.45-2.62 (m, 4 H), 2.64-2.72 (m, 2 H ), 2.72-2.81 (m, 1 H), 2.83-2.91 (m, 1 H), 2.97-3.12 (m, 2 H), 3.40-3.50 (m, 2 H), 3.52-3.68 (m, 2 H ), 3.79-3.89 (m, 2 H), 3.89-3.98 (m, 1 H), 4.15 (dd, 2 H), 4.45-4.55 (m, 1 H), 4.60-4.69 (m, 1 H), 7.44-7.48 (m, 2 H), 7.48-7.54 (m, 4 H), 7.65 (s, 2 H), 8.11-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 596.3 [M + H] ⁺ , 618.3 [M + Na] ⁺ .
Example 229: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-methylpiperidine-1-carboxamide
1- (2,6-Diphenylisonicotinoyl) -4- [1- (piperidin-4-ylcarbonyl) piperidin-4-yl] piperazine (150 mg, 0.279 mmol) obtained in Example 60 in chloroform (containing Methyl isocyanate (48 mg, 0.837 mmol) was added to a solution of (amylene) (3 ml) and stirred at room temperature for 3 hours. After completion of the reaction, the reaction solution was washed with water and saturated brine, and the organic layer was dried over anhydrous magnesium sulfate. After concentration, the residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (159 mg, 0.167 mmol, 96%) as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.47 (m, 2 H), 1.65-1.81 (m, 4 H), 1.81-1.95 (m, 2 H), 2.46-2.59 (m, 4 H ), 2.60-2.72 (m, 3 H), 2.76-2.88 (m, 5 H), 2.99-3.11 (m, 1 H), 3.40-3.50 (m, 2 H), 3.79-3.90 (m, 2 H ), 3.90-4.00 (m, 3 H), 4.39-4.46 (m, 1 H), 4.60-4.71 (m, 1 H), 7.43-7.48 (m, 2 H), 7.49-7.55 (m, 4 H ), 7.65 (s, 2 H), 8.10-8.20 (m, 4 H).
MS ESI / APCI Dual (+): 595.4 [M + H] ⁺ , 617.3 [M + Na] ⁺ .

Example 230: tert-butyl {3- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -3-oxopropyl} carbamate
The reaction was carried out in substantially the same manner as in Example 211 except that N- (tert-butoxycarbonyl) -alanine was used instead of N-acetylglycine to give the title compound (188 mg, 0.265 mmol, 95%) as a colorless product. Obtained as amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.33-1.50 (m, 11 H), 1.56-1.98 (m, 6 H), 2.45-2.62 (m, 6 H), 2.64-2.77 (m, 4 H ), 2.99-3.11 (m, 2 H), 3.36-3.50 (m, 4 H), 3.80-3.91 (m, 3 H), 3.91-4.01 (m, 1 H), 4.50-4.60 (m, 1 H ), 4.61-4.71 (m, 1 H), 5.25-5.34 (m, 1 H), 7.43-7.49 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 709.4 [M + H] ⁺ .

Example 231: 3- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] -3-oxo Propan-1-amine
tert-butyl [(1S) -2- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidin-1-yl] Tert-butyl {3- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine- instead of -1- (hydroxymethyl) -2-oxoethyl] carbamate 1-yl} carbonyl) piperidin-1-yl] -3-oxopropyl} carbamate was used substantially in the same manner as in Example 219 to give the title compound (131 mg, 0.215 mmol, 81%) Was obtained as a colorless amorphous.
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.47 (m, 2 H), 1.51-2.03 (m, 6 H), 2.42-2.62 (m, 6 H), 2.64-2.77 (m, 4 H ), 2.94-3.11 (m, 4 H), 3.40-3.50 (m, 2 H), 3.80-3.88 (m, 2 H), 3.89-4.00 (m, 2 H), 4.54-4.62 (m, 1 H ), 4.62-4.70 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.12-8.17 (m, 4 H).
MS ESI / APCI Dual (+): 609.3 [M + H] ⁺ .
A reaction substantially similar to that of Example 61 or 141 was carried out using the corresponding reagent to give the compounds of Examples 232 to 243.
Example 232: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-isobutyrylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 608.4 [M + H] ⁺ .
Example 233: 1- (1-{[1- (2,2-dimethylpropanoyl) piperidin-4-yl] carbonyl} piperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.28 (s, 9 H), 1.35-1.48 (m, 2 H), 1.66-1.80 (m, 4 H), 1.82-1.95 (m, 2 H), 2.47-2.62 (m, 4 H), 2.64-2.78 (m, 3 H), 2.82-2.93 (m, 2 H), 3.02-3.10 (m, 1 H), 3.40-3.50 (m, 2 H), 3.80-3.90 (m, 2 H), 3.93-4.01 (m, 1 H), 4.38-4.47 (m, 2 H), 4.62-4.71 (m, 1 H), 7.45-7.48 (m, 2 H), 7.50-7.53 (m, 4 H), 7.65 (s, 2 H), 8.13-8.16 (m, 4 H).
MS APCI (+): 622.4 [M + H] ⁺ , 644.3 [M + Na] ⁺ .

Example 234: 1- (1-{[1- (cyclopropylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 0.72-0.77 (m, 2 H), 0.92-1.02 (m, 2 H), 1.23-1.78 (m, 6 H), 1.83-1.95 (m, 3 H ), 2.48-2.62 (m, 4 H), 2.65-2.78 (m, 4 H), 3.03-3.21 (m, 2 H), 3.44-3.48 (m, 2 H), 3.81-3.89 (m, 2 H ), 3.95-4.01 (m, 1 H), 4.23-4.30 (m, 1 H), 4.53-4.61 (m, 1 H), 4.63-4.70 (m, 1 H), 7.45-7.53 (m, 6 H ), 7.65 (s, 2 H), 8.13-8.16 (m, 4 H).
MS APCI (+): 606.4 [M + H] ⁺ .
Example 235: 1- (1-{[1- (cyclobutylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.47 (m, 2 H), 1.56-1.99 (m, 8 H), 2.08-2.19 (m, 2 H), 2.30-2.38 (m, 2 H ), 2.47-2.60 (m, 4 H), 2.63-2.73 (m, 4 H), 2.93-3.09 (m, 2 H), 3.21-3.28 (m, 1 H), 3.42-3.48 (m, 2 H ), 3.73-3.80 (m, 1 H), 3.81-3.89 (m, 2 H), 3.92-3.99 (m, 1 H), 4.53-4.60 (m, 1 H), 4.62-4.69 (m, 1 H ), 7.44-7.53 (m, 6 H), 7.65 (s, 2 H), 8.13-8.16 (m, 4 H).
MS APCI (+): 620.4 [M + H] ⁺ .
Example 236: 1- (1-{[1- (cyclohexylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.19-1.95 (m, 19 H), 2.42-2.75 (m, 8 H), 3.01-3.10 (m, 2 H), 3.41-3.49 (m, 2 H), 3.80-3.90 (m, 2 H), 3.93-4.01 (m, 2 H), 4.57-4.69 (m, 2 H), 7.44-7.54 (m, 6 H), 7.65 (s, 2 H) , 8.13-8.16 (m, 4 H).
MS APCI (+): 648.5 [M + H] ⁺ .

Example 237: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-phenylpiperidine-1-carboxamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.49 (m, 2 H), 1.72-1.96 (m, 6 H), 2.47-2.63 (m, 4 H), 2.65-2.75 (m, 3 H ), 2.95-3.02 (m, 2 H), 3.03-3.12 (m, 1 H), 3.40-3.49 (m, 2 H), 3.80-3.89 (m, 2 H), 3.93-4.01 (m, 1 H ), 4.05-4.12 (m, 2 H), 4.63-4.70 (m, 1 H), 6.35 (s, 1 H), 7.01-7.05 (m, 1 H), 7.25-7.30 (m, 2 H), 7.32-7.35 (m, 2 H), 7.45-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.17 (m, 4 H).
MS APCI (+): 657.3 [M + H] ⁺ .
Example 238: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl)-N, N-dimethylpiperidine-1-sulfonamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.47 (m, 2 H), 1.73-1.94 (m, 6 H), 2.47-2.62 (m, 5 H), 2.65-2.72 (m, 2 H ), 2.81 (s, 6 H), 2.82-2.89 (m, 2 H), 3.02-3.09 (m, 1 H), 3.42-3.48 (m, 2 H), 3.66-3.72 (m, 2 H), 3.81-3.89 (m, 2 H), 3.90-3.96 (m, 1 H), 4.63-4.69 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.16 (m, 4 H).
MS APCI (+): 645.3 [M + H] ⁺ , 667.1 [M + Na] ⁺ .
Example 239: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[1- (isoxazol-5-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.49 (m, 2 H), 1.75-1.96 (m, 6 H), 2.47-2.63 (m, 4 H), 2.65-2.72 (m, 2 H ), 2.80-2.86 (m, 1 H), 2.97-3.12 (m, 2 H), 3.23-3.31 (m, 1 H), 3.41-3.50 (m, 2 H), 3.81-3.90 (m, 2 H ), 3.93-4.00 (m, 1 H), 4.16-4.23 (m, 1 H), 4.54-4.62 (m, 1 H), 4.63-4.69 (m, 1 H), 6.75 (d, J = 1.83 Hz , 1 H), 7.45-7.48 (m, 2 H), 7.50-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.17 (m, 4 H), 8.31 (d, J = 1.83 Hz, 1 H).
MS APCI (+): 633.4 [M + H] ⁺ , 655.3 [M + Na] ⁺ .

Example 240: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-isonicotinoylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.34-1.48 (m, 2 H), 1.61-1.68 (m, 1 H), 1.75-1.96 (m, 5 H), 2.46-2.63 (m, 4 H ), 2.64-2.73 (m, 2 H), 2.76-2.84 (m, 1 H), 2.90-2.98 (m, 1 H), 3.02-3.12 (m, 2 H), 3.41-3.49 (m, 2 H ), 3.66-3.73 (m, 1 H), 3.80-3.89 (m, 2 H), 3.92-3.99 (m, 1 H), 4.62-4.70 (m, 2 H), 7.27-7.29 (m, 2 H ), 7.44-7.48 (m, 2 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.16 (m, 4 H), 8.68-8.70 (m, 2 H).
MS APCI (+): 643.3 [M + H] ⁺ .
Example 241 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -N-ethylpiperidine-1-carboxamide
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.14 (t, J = 7.11 Hz, 3 H), 1.35-1.48 (m, 2 H), 1.66-1.81 (m, 4 H), 1.82-1.94 (m , 2 H), 2.46-2.73 (m, 7 H), 2.80-2.88 (m, 2 H), 3.01-3.09 (m, 1 H), 3.23-3.30 (m, 2 H), 3.41-3.49 (m , 2 H), 3.80-3.89 (m, 2 H), 3.92-4.00 (m, 3 H), 4.34-4.40 (m, 1 H), 4.62-4.69 (m, 1 H), 7.45-7.48 (m , 2 H), 7.49-7.53 (m, 4 H), 7.65 (s, 2 H) 8.13-8.16 (m, 4 H).
MS APCI (+): 609.5 [M + H] ⁺ , 631.4 [M + Na] ⁺ .
Example 242: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[1- (2-furoyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ1.35-1.49 (m, 2 H), 1.73-1.97 (m, 6 H), 2.46-2.63 (m, 4 H), 2.64-2.74 (m, 2 H), 2.76-2.83 (m, 1 H), 2.98-3.15 (m, 3 H), 3.40-3.51 (m, 2 H), 3.79-3.91 (m, 2 H), 3.93-4.03 (m, 1 H), 4.44-4.60 (m, 2 H), 4.63-4.70 (m, 1 H), 6.47 (dd, J = 3.67, 1.83 Hz, 1 H), 6.95-6.97 (m, 1 H), 7.44- 7.49 (m, 3 H), 7.49-7.54 (m, 4 H), 7.65 (s, 2 H), 8.13-8.17 (m, 4 H).
MS APCI (+): 632.4 [M + H] ⁺ .

Example 243: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[1- (pyrrolidin-1-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazine
¹ H-NMR (600 MHz, CDCl ₃ ) δ 1.35-1.48 (m, 2 H), 1.66-1.72 (m, 2 H), 1.73-1.94 (m, 8 H), 2.48-2.60 (m, 4 H ), 2.60-2.79 (m, 5 H), 3.01-3.09 (m, 1 H), 3.32-3.39 (m, 4 H), 3.42-3.49 (m, 2 H), 3.74-3.89 (m, 4 H ), 3.93-4.01 (m, 1 H), 4.63-4.71 (m, 1 H), 7.44-7.48 (m, 2 H), 7.49-7.53 (m, 4 H), 7.65 (s, 2 H), 8.13-8.16 (m, 4 H).
MS APCI (+): 635.4 [M + H] ⁺ , 657.4 [M + Na] ⁺ .
A reaction substantially similar to that of Example 3 or 45 was carried out using the corresponding reagents to give the compounds of Examples 244 to 532.
Example 244: 1- (1-acetylpiperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 469.4 [M + H] ⁺ .
Example 245: 1- (2,6-diphenylisonicotinoyl) -4- [1- (isoxazol-5-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 522.4 [M + H] ⁺ .
Example 246: ethyl {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} (oxo) acetate
MS APCI (+): 527.4 [M + H] ⁺ .
Example 247: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 545.4 [M + H] ⁺ .

Example 248: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methyl-1,2,3-thiadiazol-5-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 553.3 [M + H] ⁺ .
Example 249: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-phenylpropanoyl) piperidin-4-yl] piperazine
MS APCI (+): 559.4 [M + H] ⁺ .
Example 250: 4-methylphenyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 561.4 [M + H] ⁺ .
Example 251: 5- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) imidazolidine-2,4-dione
MS APCI (+): 567.4 [M + H] ⁺ .
Example 252: 1- (2,6-diphenylisonicotinoyl) -4- (1-propionylpiperidin-4-yl) piperazine
MS APCI (+): 483.4 [M + H] ⁺ .
Example 253: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-methylbutanoyl) piperidin-4-yl] piperazine
MS APCI (+): 511.4 [M + H] ⁺ .
Example 254: 1- [1- (cyclopentylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 523.4 [M + H] ⁺ .

Example 255: Methyl 3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropanoate
MS APCI (+): 527.4 [M + H] ⁺ .
Example 256: 1-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) imidazolidin-2-one
MS APCI (+): 539.4 [M + H] ⁺ .
Example 257: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 545.4 [M + H] ⁺ .
Example 258: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methylpiperazin-1-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 553.4 [M + H] ⁺ .

Example 259: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-ethylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 559.4 [M + H] ⁺ .
Example 260: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-fluoro-4-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 563.4 [M + H] ⁺ .
Example 261: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3,5,5-trimethylhexanoyl) piperidin-4-yl] piperazine
MS APCI (+): 567.5 [M + H] ⁺ .
Example 262: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-propylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 573.4 [M + H] ⁺ .
Example 263: 1- {1-[(4-chlorophenyl) acetyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 579.4 [M + H] ⁺ .

Example 264: Methyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 485.4 [M + H] ⁺ .
Example 265: 1- (2,6-diphenylisonicotinoyl) -4- (1-pentanoylpiperidin-4-yl) piperazine
MS APCI (+): 511.4 [M + H] ⁺ .
Example 266: 1- (2,6-diphenylisonicotinoyl) -4- [1- (pyrrolidin-1-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 524.4 [M + H] ⁺ .
Example 267: 1- (2,6-diphenylisonicotinoyl) -4- (1-heptanoylpiperidin-4-yl) piperazine
MS APCI (+): 539.5 [M + H] ⁺ .
Example 268: 1- (2,6-diphenylisonicotinoyl) -4- [1- (phenylacetyl) piperidin-4-yl] piperazine
MS APCI (+): 545.4 [M + H] ⁺ .
Example 269: 1- (2,6-diphenylisonicotinoyl) -4- (1-octanoylpiperidin-4-yl) piperazine
MS APCI (+): 553.5 [M + H] ⁺ .

Example 270: 1- [1- (2,3-dimethylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 559.4 [M + H] ⁺ .
Example 271: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-fluoro-3-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 563.4 [M + H] ⁺ .
Example 272: 1- (2,6-diphenylisonicotinoyl) -4- (1-nonanoylpiperidin-4-yl) piperazine
MS APCI (+): 567.5 [M + H] ⁺ .
Example 273: 1- (2,6-diphenylisonicotinoyl) -4- [1- (mesitylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 573.4 [M + H] ⁺ .
Example 274: 1- [1- (cyclopropylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 495.4 [M + H] ⁺ .
Example 275: 1- (2,6-diphenylisonicotinoyl) -4- (1-hexanoylpiperidin-4-yl) piperazine
MS APCI (+): 525.5 [M + H] ⁺ .

Example 276: methyl 4- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -4-oxobutanoate
MS APCI (+): 541.4 [M + H] ⁺ .
Example 277: Phenyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 547.4 [M + H] ⁺ .
Example 278: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-propylpentanoyl) piperidin-4-yl] piperazine
MS APCI (+): 553.5 [M + H] ⁺ .
Example 279: 1- [1- (3,4-dimethylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 559.4 [M + H] ⁺ .
Example 280: 1- [1- (2-chlorobenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 566.4 [M + H] ⁺ .

Example 281: 1- (2,6-diphenylisonicotinoyl) -4- [1- (pyridin-3-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 532.4 [M + H] ⁺ .
Example 282: 1- [1- (2,3-difluoro-4-methylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 581.4 [M + H] ⁺ .
Example 283: 1- (2,6-diphenylisonicotinoyl) -4- (1-isobutyrylpiperidin-4-yl) piperazine
MS APCI (+): 497.4 [M + H] ⁺ .
Example 284: methyl {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} (oxo) acetate
MS APCI (+): 513.4 [M + H] ⁺ .
Example 285: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-ethylbutanoyl) piperidin-4-yl] piperazine
MS APCI (+): 525.5 [M + H] ⁺ .
Example 286: Ethyl 3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropanoate
MS APCI (+): 541.4 [M + H] +.
Example 287: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-fluorobenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 549.4 [M + H] ⁺ .

Example 288: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-ethylhexanoyl) piperidin-4-yl] piperazine
MS APCI (+): 553.5 [M + H] ⁺ .
Example 289: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-methoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 561.4 [M + H] ⁺ .
Example 290: 1- [1- (3-chlorobenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 566.3 [M + H] ⁺ .
Example 291: 1- (2,6-diphenylisonicotinoyl) -4- (1-isonicotinoylpiperidin-4-yl) piperazine
MS APCI (+): 532.4 [M + H] ⁺ .
Example 292: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-ethoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 575.4 [M + H] ⁺ .

Example 293: 1- [1- (2,6-difluoro-3-methylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 581.4 [M + H] ⁺ .
Example 294: 1- (1-butyrylpiperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 497.4 [M + H] ⁺ .
Example 295: Propyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 513.4 [M + H] ⁺ .
Example 296: 1- [1- (3,3-dimethylbutanoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 525.5 [M + H] ⁺ .
Example 297: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) pyrazine
MS APCI (+): 533.4 [M + H] ⁺ .
Example 298: 2,2-dimethylpropyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 541.5 [M + H] ⁺ .

Example 299: 1- [1- (2,5-dimethyl-3-furoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 549.4 [M + H] ⁺ .
Example 300: Methyl 5- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -5-oxopentanoate
MS APCI (+): 555.4 [M + H] ⁺ .
Example 301: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-methoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 561.4 [M + H] ⁺ .
Example 302: 1- (2,6-diphenylisonicotinoyl) -4- [1- (5-nitro-2-furoyl) piperidin-4-yl] piperazine
MS APCI (+): 566.4 [M + H] ⁺ .

Example 303: 1- (2,6-diphenylisonicotinoyl) -4- [1- (pyridin-2-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 532.4 [M + H] ⁺ .
Example 304: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1-naphthoyl) piperidin-4-yl] piperazine
MS APCI (+): 581.4 [M + H] ⁺ .
Example 305: 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] -N, N-dimethylpiperidine-1-carboxamide
MS APCI (+): 498.4 [M + H] ⁺ .
Example 306: Isopropyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 513.4 [M + H] ⁺ .
Example 307: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-methylpentanoyl) piperidin-4-yl] piperazine
MS APCI (+): 525.5 [M + H] ⁺ .

Example 308: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(2-methoxyethoxy) acetyl] piperidin-4-yl} piperazine
MS ESI (+): 543.4 [M + H] ⁺ .
Example 309: 1- {1-[(1,3-dimethyl-1H-pyrazol-5-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 549.4 [M + H] ⁺ .
Example 310: Ethyl 4- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -4-oxobutanoate
MS APCI (+): 555.4 [M + H] ⁺ .
Example 311: 1- (2,6-diphenylisonicotinoyl) -4- [1- (phenoxyacetyl) piperidin-4-yl] piperazine
MS APCI (+): 561.4 [M + H] ⁺ .
Example 312: 1- [1- (2,3-difluorobenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 567.4 [M + H] ⁺ .
Example 313: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-nitrobenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 576.4 [M + H] ⁺ .
Example 314: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-naphthoyl) piperidin-4-yl] piperazine
MS APCI (+): 581.4 [M + H] ⁺ .

Example 315: Ethyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 499.4 [M + H] ⁺ .
Example 316: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-furoyl) piperidin-4-yl] piperazine
MS APCI (+): 521.4 [M + H] ⁺ .
Example 317: 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] -N, N-diethylpiperidine-1-carboxamide
MS APCI (+): 526.5 [M + H] ⁺ .
Example 318: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-thienylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 537.4 [M + H] ⁺ .

Example 319: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 545.4 [M + H] ⁺ .
Example 320: 1- {1-[(3,5-dimethylisoxazol-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 550.4 [M + H] ⁺ .
Example 321: 1- [1- (3,5-dimethylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 559.4 [M + H] ⁺ .
Example 322: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-methoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 561.4 [M + H] ⁺ .
Example 323: 1- [1- (2,6-difluorobenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 567.4 [M + H] ⁺ .

Example 324: Methyl 6- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -6-oxohexanoate
MS APCI (+): 569.5 [M + H] ⁺ .
Example 325: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-nitrobenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 576.4 [M + H] ⁺ .
Example 326: 1- (1-decanoylpiperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 581.5 [M + H] ⁺ .
Example 327: 1- [1- (2-chloro-6-fluoro-3-methylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 599.4 [M + H] ⁺ .
Example 328: 4- (methoxycarbonyl) phenyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 605.4 [M + H] ⁺ .
Example 329: 1- (2,6-diphenylisonicotinoyl) -4- {1- [2- (trifluoromethoxy) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 615.4 [M + H] ⁺ .

Example 330: 1- (1-{[1- (4-chlorophenyl) cyclopentyl] carbonyl} piperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 633.5 [M + H] ⁺ .
Example 331: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2,4,6-trifluorobenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 585.4 [M + H] ⁺ .
Example 332: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-phenoxybutanoyl) piperidin-4-yl] piperazine
MS APCI (+): 589.5 [M + H] ⁺ .
Example 333: 1- {1-[(3-tert-butyl-1-methyl-1H-pyrazol-5-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) Piperazine
MS APCI (+): 591.5 [M + H] ⁺ .
Example 334: 1- [1- (6-Chloro-2-fluoro-3-methylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 599.4 [M + H] ⁺ .

Example 335: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (trifluoromethoxy) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 615.4 [M + H] ⁺ .
Example 336: 1- {1- [5- (4-chlorophenyl) -2-methyl-3-furoyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 645.4 [M + H] ⁺ .
Example 337: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2,3,6-trifluorobenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 585.4 [M + H] ⁺ .
Example 338: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-phenoxybutanoyl) piperidin-4-yl] piperazine
MS APCI (+): 589.5 [M + H] ⁺ .
Example 339: 3- (trifluoromethyl) phenyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 615.4 [M + H] ⁺ .

Example 340: 1- {1- [5- (3,5-dichlorophenoxy) -2-furoyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 681.4 [M + H] ⁺ .
Example 341: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperidine-1-carbaldehyde
MS APCI (+): 566.4 [M + H] ⁺ .
Example 342: 1- {1-[(3S, 5S, 7S) -1-adamantylcarbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 589.5 [M + H] ⁺ .
Example 343: 1- (2,6-diphenylisonicotinoyl) -4- {1- [3- (trifluoromethyl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 599.4 [M + H] ⁺ .
Example 344: 1- [1- (biphenyl-4-ylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 607.5 [M + H] ⁺ .
Example 345: 1- {1-[(3-bromo-2-thienyl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 615.3 [M + H] ⁺ .

Example 346: 1- (1-{[1- (4-chlorophenyl) -5- (trifluoromethyl) -1H-pyrazol-4-yl] carbonyl} piperidin-4-yl) -4- (2,6 -Diphenylisonicotinoyl) piperazine
MS APCI (+): 699.4 [M + H] ⁺ .
Example 347: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-methyl-3-nitrobenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 590.4 [M + H] ⁺ .
Example 348: 1- {1-[(4-chlorophenoxy) acetyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 595.4 [M + H] ⁺ .
Example 349: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (trifluoromethyl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 599.4 [M + H] ⁺ .
Example 350: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzonitrile
MS APCI (+): 556.4 [M + H] ⁺ .

Example 351 1- [1- (4-tert-butylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 587.5 [M + H] ⁺ .
Example 352: 1- [1- (3,4-dimethoxybenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 591.5 [M + H] ⁺ .
Example 353: 2-naphthyl 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxylate
MS APCI (+): 597.4 [M + H] ⁺ .
Example 354: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-pentylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 601.5 [M + H] ⁺ .
Example 355: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(5-methyl-2-phenyl-2H-1,2,3-triazol-4-yl) carbonyl] piperidine- 4-Il} piperazine
MS APCI (+): 612.5 [M + H] ⁺ .
Example 356: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (pentyloxy) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 617.5 [M + H] ⁺ .

Example 357: 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl]-N, N-diisopropylpiperidine-1-carboxamide
MS APCI (+): 554.5 [M + H] ⁺ .
Example 358: N- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) benzamide
MS APCI (+): 588.5 [M + H] ⁺ .
Example 359: 1- [1- (2,4-dimethoxybenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 591.5 [M + H] ⁺ .
Example 360: Ethyl 7- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -7-oxoheptanoate
MS APCI (+): 597.5 [M + H] ⁺ .
Example 361: 1- (2,6-diphenylisonicotinoyl) -4- {1- [5-methyl-2- (trifluoromethyl) -3-furoyl] piperidin-4-yl} piperazine
MS APCI (+): 603.4 [M + H] ⁺ .
Example 362: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[2-methyl-6- (trifluoromethyl) pyridin-3-yl] carbonyl} piperidin-4-yl) piperazine
MS APCI (+): 614.4 [M + H] ⁺ .

Example 363: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-heptylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 629.6 [M + H] ⁺ .
Example 364: 4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] -N-methyl-N-phenylpiperidine-1-carboxamide
MS APCI (+): 560.5 [M + H] ⁺ .
Example 365: Methyl 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoate
MS APCI (+): 589.4 [M + H] ⁺ .
Example 366: 1- [1- (5-tert-butyl-2-methyl-3-furoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 591.5 [M + H] ⁺ .

Example 367: Methyl 8- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -8-oxooctanoate
MS APCI (+): 597.5 [M + H] +.
Example 368: 1- [1- (4-butoxybenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 603.5 [M + H] ⁺ .
Example 369: 1- (2,6-diphenylisonicotinoyl) -4- {1- [3- (trifluoromethoxy) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 615.4 [M + H] ⁺ .
Example 370: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (hexyloxy) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 631.5 [M + H] ⁺ .
Example 371: N, N-dibutyl-4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidine-1-carboxamide
MS APCI (+): 582.5 [M + H] ⁺ .
Example 372: 3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropanenitrile
MS APCI (+): 494.4 [M + H] ⁺ .

Example 373: 1- (2,6-diphenylisonicotinoyl) -4- [1- (isoxazol-5-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 522.4 [M + H] ⁺ .
Example 374: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-methyl-1H-imidazol-5-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 535.4 [M + H] ⁺ .
Example 375: (5S) -5-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) pyrrolidin-2-one
MS APCI (+): 538.5 [M + H] ⁺ .
Example 376: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) aniline
MS APCI (+): 546.4 [M + H] ⁺ .

Example 377: 5-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) pyridin-2-ol
MS APCI (+): 548.4 [M + H] ⁺ .
Example 378: 5-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -2-methylaniline
MS APCI (+): 560.5 [M + H] ⁺ .
Example 379: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzene-1,2-diol
MS APCI (+): 563.4 [M + H] ⁺ .
Example 380: 1- [1- (3-cyclohexylpropanoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 565.5 [M + H] ⁺ .

Example 381: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(3-methoxycyclohexyl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 567.5 [M + H] ⁺ .
Example 382: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1-oxoacetone
MS APCI (+): 497.4 [M + H] ⁺ .
Example 383: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-methyl-1H-imidazol-2-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 535.4 [M + H] ⁺ .
Example 384: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1,3-thiazol-4-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 538.4 [M + H] ⁺ .
Example 385: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) aniline
MS APCI (+): 546.4 [M + H] ⁺ .

Example 386: 2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1- (2-furyl) -2-oxoethanone
MS APCI (+): 549.4 [M + H] ⁺ .
Example 387: N- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) aniline
MS APCI (+): 560.5 [M + H] ⁺ .
Example 388: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -6-methylpyridin-2-ol
MS APCI (+): 562.4 [M + H] ⁺ .
Example 389: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzene-1,4-diol
MS APCI (−): 561.4 [MH]-.
Example 390: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methylcyclohexyl) acetyl] piperidin-4-yl} piperazine
MS APCI (+): 565.5 [M + H] ⁺ .
Example 391: 1- (2,6-diphenylisonicotinoyl) -4- [1- (methoxyacetyl) piperidin-4-yl] piperazine
MS APCI (+): 499.4 [M + H] ⁺ .

Example 392: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(2S) -tetrahydrofuran-2-ylcarbonyl] piperidin-4-yl} piperazine
MS APCI (+): 525.4 [M + H] ⁺ .
Example 393: 1- [1- (cyclopent-2-en-1-ylacetyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 535.5 [M + H] ⁺ .
Example 394: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1-methyl-L-prolyl) piperidin-4-yl] piperazine
MS APCI (−): 536.4 [MH]-.
Example 395: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(6-methylpyridin-3-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 546.4 [M + H] ⁺ .
Example 396: 1- (2,6-diphenylisonicotinoyl) -4- {1- [3- (1H-imidazol-4-yl) propanoyl] piperidin-4-yl} piperazine
MS APCI (+): 549.5 [M + H] ⁺ .

Example 397: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclohexanol
MS APCI (+): 553.5 [M + H] ⁺ .
Example 398: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -6-methylaniline
MS APCI (+): 560.5 [M + H] ⁺ .
Example 399: 2-amino-4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol
MS APCI (−): 560.4 [MH] ^- .
Example 400: 1- [1- (1-Acetylprolyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 566.5 [M + H] ⁺ .
Example 401: (1R) -1-cyclohexyl-2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethanol
MS APCI (+): 567.5 [M + H] ⁺ .

Example 402: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(2R) -tetrahydrofuran-2-ylcarbonyl] piperidin-4-yl} piperazine
MS APCI (+): 525.4 [M + H] ⁺ .
Example 403: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(3-methylisoxazol-4-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 536.4 [M + H] ⁺ .
Example 404: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) imidazolidin-2-one
MS APCI (+): 539.4 [M + H] ⁺ .
Example 405: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol
MS APCI (+): 547.4 [M + H] ⁺ .
Example 406: 1- [1- (cyclohex-1-en-1-ylacetyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 549.5 [M + H] ⁺ .
Example 407: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzonitrile
MS APCI (+): 556.4 [M + H] ⁺ .

Example 408: 2-amino-5-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol
MS APCI (+): 562.4 [M + H] ⁺ .
Example 409: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzene-1,3-diol
MS APCI (+): 563.4 [M + H] ⁺ .
Example 410: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-piperidin-1-ylpropanoyl) piperidin-4-yl] piperazine
MS APCI (+): 566.5 [M + H] ⁺ .
Example 411: (1S) -1-cyclohexyl-2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethanol
MS APCI (+): 567.5 [M + H] ⁺ .
Example 412: 1- [1- (cyclopropylacetyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 509.4 [M + H] ⁺ .

Example 413: 5- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -5-oxopentan-2-one
MS APCI (+): 525.4 [M + H] ⁺ .
Example 414: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(5-methylisoxazol-3-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 536.4 [M + H] ⁺ .
Example 415: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-methyl-1-oxopentan-2-one
MS APCI (+): 539.5 [M + H] ⁺ .
Example 416: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol
MS APCI (+): 547.4 [M + H] ⁺ .
Example 417: 6-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -4,5-dihydropyridazine-3 (2H)- on
MS APCI (+): 551.5 [M + H] ⁺ .
Example 418: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -6-methylphenol
MS APCI (+): 561.4 [M + H] ⁺ .
Example 419: 4-amino-2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol
MS APCI (−): 560.4 [MH]-.

Example 420: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-fluoro-4-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 563.4 [M + H] ⁺ .
Example 421: (6S) -6-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) dihydropyrimidine-2,4 (1H, 3H) -Dione
MS APCI (+): 567.5 [M + H] ⁺ .
Example 422: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1-oxobutan-2-one
MS APCI (+): 511.4 [M + H] ⁺ .
Example 423: 1- (2,6-diphenylisonicotinoyl) -4- [1- (tetrahydrofuran-3-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 525.4 [M + H] ⁺ .
Example 424: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(5-methylisoxazol-4-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 536.5 [M + H] ⁺ .
Example 425: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -4-methyl-1-oxopentan-2-one
MS APCI (+): 539.5 [M + H] ⁺ .

Example 426: 1- [1- (cyclohexylacetyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 551.5 [M + H] ⁺ .
Example 427: (4R) -4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -1,3-thiazolidine-2- on
MS APCI (+): 556.4 [M + H] ⁺ .
Example 428: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -5-methylphenol
MS APCI (+): 561.4 [M + H] ⁺ .
Example 429: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1,2,5-trimethyl-1H-pyrrol-3-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 562.5 [M + H] ⁺ .

Example 430: 1- (2,6-diphenylisonicotinoyl) -4- {1- [fluoro (phenyl) acetyl] piperidin-4-yl} piperazine
MS APCI (+): 563.4 [M + H] ⁺ .
Example 431: 5- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) imidazolidine-2,4-dione
MS APCI (+): 567.5 [M + H] ⁺ .
Example 432: 1- (1-{[(4R) -5,5-dimethyl-1,3-thiazolidin-4-yl] carbonyl} piperidin-4-yl) -4- (2,6-diphenylisonicoti (Noyl) piperazine
MS APCI (+): 570.5 [M + H] ⁺ .
Example 433: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1H-pyrrol-2-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 520.4 [M + H] ⁺ .
Example 434: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1-oxopentan-2-one
MS APCI (+): 525.4 [M + H] ⁺ .
Example 435: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methyl-1,2,5-oxadiazol-3-yl) carbonyl] piperidin-4-yl} Piperazine
MS APCI (+): 537.4 [M + H] ⁺ .

Example 436: 5- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -4-methyl-5-oxopentan-2-one
MS APCI (+): 539.5 [M + H] ⁺ .
Example 437: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -5-methylpyrazine
MS APCI (+): 547.4 [M + H] ⁺ .
Example 438: 1- [1- (3-cyclopentylpropanoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 551.5 [M + H] ⁺ .
Example 439: 1- [1- (bicyclo [4.2.0] octa-1,3,5-trien-7-ylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) Piperazine
MS APCI (+): 557.5 [M + H] ⁺ .
Example 440: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -2-methylphenol
MS APCI (+): 561.5 [M + H] ⁺ .
Example 441: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzene-1,3-diol
MS APCI (+): 563.4 [M + H] ⁺ .
Example 442: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-ethyl-3-methyl-1H-pyrazol-5-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 563.5 [M + H] ⁺ .

Example 443: (5R) -5- (3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropyl) dihydrofuran- 2 (3H) -ON
MS APCI (+): 567.5 [M + H] ⁺ .
Example 444: 1- [1- (1-benzofuran-3-ylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 571.4 [M + H] ⁺ .
Example 445: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1H-imidazol-2-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 521.4 [M + H] ⁺ .
Example 446: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-methyl-2-furoyl) piperidin-4-yl] piperazine
MS APCI (+): 525.4 [M + H] ⁺ .

Example 447: 1- [1- (cyclopentylacetyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 537.5 [M + H] ⁺ .
Example 448: (1S, 2R) -2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) cyclopentanol
MS APCI (+): 539.5 [M + H] ⁺ .
Example 449: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(methylsulfonyl) acetyl] piperidin-4-yl} piperazine
MS APCI (+): 547.4 [M + H] ⁺ .
Example 450: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-methyl-1,3-thiazol-5-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 552.4 [M + H] ⁺ .
Example 451 2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxo-1-phenylethanone
MS APCI (+): 559.4 [M + H] ⁺ .
Example 452: 5-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -2-methylphenol
MS APCI (+): 561.4 [M + H] ⁺ .
Example 453: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzene-1,2-diol
MS APCI (+): 563.4 [M + H] ⁺ .

Example 454: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4-nitro-1H-pyrrol-2-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 565.4 [M + H] ⁺ .
Example 455: 2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -6-methoxyphenol
MS APCI (+): 577.4 [M + H] ⁺ .
Example 456: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1,2,3,4-tetrahydronaphthalen-2-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 585.5 [M + H] ⁺ .
Example 457: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -2,6-dimethoxyphenol
MS APCI (+): 607.5 [M + H] ⁺ .
Example 458: 4-{[5-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -2-furyl] methyl} morpholine
MS APCI (+): 620.5 [M + H] ⁺ .
Example 459: 1- {1- [5- (4-chlorophenyl) -2-furoyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 631.4 [M + H] ⁺ .

Example 460: 1- [1- (biphenyl-2-ylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 607.5 [M + H] ⁺ .
Example 461 1- {1-[(4′-tert-butylbiphenyl-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 663.5 [M + H] ⁺ .
Example 462: 1- [1- (2,3-dihydro-1H-inden-2-ylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 571.5 [M + H] ⁺ .
Example 463: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl)-N, N-dimethylaniline
MS APCI (+): 574.5 [M + H] ⁺ .
Example 464: 1-butyl-3- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) urea
MS APCI (+): 583.5 [M + H] ⁺ .
Example 465: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-methyl-1H-imidazol-4-yl) acetyl] piperidin-4-yl} piperazine
MS APCI (+): 549.5 [M + H] ⁺ .

Example 466: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-isopropoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 589.5 [M + H] ⁺ .
Example 467: 4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl)-N, N-diethylaniline
MS APCI (+): 602.5 [M + H] ⁺ .
Example 468: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (methylsulfonyl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 609.5 [M + H] ⁺ .
Example 469: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3,4,5-trimethoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 621.5 [M + H] ⁺ .
Example 470: 1- (2,6-diphenylisonicotinoyl) -4- {1- [3- (methylsulfonyl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 609.4 [M + H] ⁺ .
Example 471: 2- (3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropyl) cyclododecanone
MS APCI (+): 663.6 [M + H] ⁺ .

Example 472: N- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) -2-fluamide
MS APCI (+): 578.4 [M + H] ⁺ .
Example 473: 3- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) -1H-indole
MS APCI (+): 584.5 [M + H] ⁺ .
Example 474: 4- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -4-oxo-1-phenylbutan-1-one
MS APCI (+): 587.5 [M + H] ⁺ .
Example 475: 1- {1-[(4-tert-butylcyclohexyl) carbonyl] piperidin-4-yl} -4- (2,6- MS APCI (+): diphenylisonicotinoyl) piperazine
MS APCI (+): 593.6 [M + H] ⁺ .

Example 476: 1- [4- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethoxy) phenyl] ethanone
MS APCI (+): 603.5 [M + H] ⁺ .
Example 477: 2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1- (1-methyl-1H-indol-3-yl) -2-oxoethanone
MS APCI (+): 612.5 [M + H] ⁺ .
Example 478: 4- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) -2,6-dimethoxyphenol
MS APCI (+): 621.5 [M + H] +.
Example 479: [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] (phenyl) methanone
MS APCI (+): 635.5 [M + H] ⁺ .
Example 480: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3- (1H-indol-3-yl) -1-oxo acetone
MS APCI (−): 610.4 [MH] ^- .

Example 481: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1H-imidazol-4-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (−): 519.4 [MH] ^- .
Example 482: 1- [2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] ethanone
MS APCI (+): 573.5 [M + H] ⁺ .
Example 483: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-methoxy-4-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 575.5 [M + H] ⁺ .
Example 484: 1- [1- (5-cyclohexylpentanoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 593.5 [M + H] ⁺ .
Example 485: 1- (2,6-diphenylisonicotinoyl) -4- {1- [5- (pyrrolidin-1-ylmethyl) -2-furoyl] piperidin-4-yl} piperazine
MS APCI (+): 604.5 [M + H] ⁺ .
Example 486: 1- [1- (cyclododecylcarbonyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 621.6 [M + H] ⁺ .

Example 487: 1- (4-chlorophenyl) -4- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -4-oxobutane-1,3 -Zeon
MS APCI (−): 633.4 [MH] ^- .
Example 488: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[(4S) -2-phenyl-1,3-thiazolidin-4-yl] carbonyl} piperidin-4-yl) Piperazine
MS APCI (+): 618.5 [M + H] ⁺ .
Example 489: 1- [3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] ethanone
MS APCI (+): 573.4 [M + H] ⁺ .
Example 490: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-methoxy-3-methylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 575.5 [M + H] ⁺ .
Example 491: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-fluoro-4-methoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 579.4 [M + H] ⁺ .

Example 492: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (1,3-oxazol-5-yl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 598.4 [M + H] ⁺ .
Example 493: 4- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1- (4-fluorophenyl) -4-oxobutane-1- on
MS APCI (+): 605.5 [M + H] ⁺ .
Example 494: 1- (2,6-diphenylisonicotinoyl) -4- {1- [4- (1,2,3-thiadiazol-4-yl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 615.4 [M + H] ⁺ .

Example 495: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-phenoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 623.5 [M + H] ⁺ .
Example 496: 1- {1- [4- (benzyloxy) benzoyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 637.5 [M + H] ⁺ .
Example 497: 1- (2,6-diphenylisonicotinoyl) -4- [1- (3-phenoxybenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 623.5 [M + H] ⁺ .
Example 498: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1,2,3-thiadiazol-4-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 539.4 [M + H] ⁺ .
Example 499: 1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] ethanone
MS APCI (+): 573.5 [M + H] ⁺ .
Example 500: 2- (3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropyl) phenol
MS APCI (+): 575.5 [M + H] ⁺ .

Example 501 4- (2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -2-oxoethyl) -2-fluorophenol
MS APCI (+): 579.4 [M + H] ⁺ .
Example 502: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[1- (pyridin-3-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) piperazine
MS APCI (+): 643.3 [M + H] ⁺ .
Example 503: 2- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1- (1H-indol-3-yl) -2-oxoethanone
MS APCI (+): 598.4 [M + H] ⁺ .
Example 504: 1- [1- (3,5-dimethoxy-4-methylbenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 605.5 [M + H] ⁺ .
Example 505: 1- (2,6-diphenylisonicotinoyl) -4- {1- [5- (piperidin-1-ylmethyl) -2-furoyl] piperidin-4-yl} piperazine
MS APCI (+): 618.5 [M + H] ⁺ .
Example 506: 1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenyl] -2,2,2-trifluoro Loethanon
MS APCI (+): 627.4 [M + H] ⁺ .

Example 507: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(4'-propylbiphenyl-4-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 649.5 [M + H] ⁺ .
Example 508: 1- (2,6-diphenylisonicotinoyl) -4- [1- (1H-inden-3-ylcarbonyl) piperidin-4-yl] piperazine
MS APCI (+): 569.5 [M + H] ⁺ .
Example 509: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -1-oxo-3-phenylacetone
MS APCI (+): 573.4 [M + H] ⁺ .
Example 510: 1- {1-[(benzyloxy) acetyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 575.5 [M + H] ⁺ .

Example 511: 1- {1-[(3R) -3,7-dimethyloct-6-enoyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 579.5 [M + H] ⁺ .
Example 512: 3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) indan-1-one
MS APCI (+): 585.4 [M + H] ⁺ .
Example 513: 2- (3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropyl) -1H-benzimidazole
MS APCI (+): 599.5 [M + H] ⁺ .
Example 514: (1S, 4S) -3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) -1,7,7- Trimethylbicyclo [2.2.1] heptan-2-one
MS APCI (+): 605.5 [M + H] ⁺ .
Example 515: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3- (4-hydroxy-3-methoxyphenyl) -1- Oxoacetone
MS APCI (+): 619.5 [M + H] ⁺ .
Example 516: 1- (2,6-diphenylisonicotinoyl) -4- (1-{[6- (2-pyrrolidin-1-ylethyl) pyridin-3-yl] carbonyl} piperidin-4-yl) piperazine
MS APCI (+): 629.5 [M + H] ⁺ .
Example 517: 1- (1-{[4- (benzyloxy) phenyl] acetyl} piperidin-4-yl) -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 651.5 [M + H] ⁺ .

Example 518: 1- (2,6-diphenylisonicotinoyl) -4- {1- [5- (2-nitrophenyl) -2-furoyl] piperidin-4-yl} piperazine
MS APCI (+): 642.4 [M + H] ⁺ .
Example 519: 1- [1- (4-cyclohexylbutanoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 579.5 [M + H] ⁺ .
Example 520: 1- [1- (2,3-dihydro-1H-inden-2-ylacetyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 585.5 [M + H] ⁺ .
Example 521: 1- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3- (4-hydroxyphenyl) -1-oxoacetone
MS APCI (+): 589.4 [M + H] ⁺ .
Example 522: (1S, 3R, 5R, 7S) -3-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) adamantane-1 -All
MS APCI (+): 605.5 [M + H] ⁺ .

Example 523: 1- [4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) benzoyl] piperidin-4-one
MS APCI (+): 656.5 [M + H] ⁺ .
Example 524: 1- (2,6-diphenylisonicotinoyl) -4- {1- [5- (4-nitrophenyl) -2-furoyl] piperidin-4-yl} piperazine
MS APCI (+): 642.4 [M + H] ⁺ .
Example 525: 1- (2,6-diphenylisonicotinoyl) -4- [1- (4-isobutylbenzoyl) piperidin-4-yl] piperazine
MS APCI (+): 587.5 [M + H] ⁺ .
Example 526: 1- (2,6-diphenylisonicotinoyl) -4- {1- [2- (trifluoromethyl) benzoyl] piperidin-4-yl} piperazine
MS APCI (+): 599.3 [M + H] ⁺ , 621.3 [M + Na] ⁺ .

Example 527: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(5-methylisoxazol-3-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 536.3 [M + H] ⁺ , 558.3 [M + Na] ⁺ .
Example 528: 1- (2,6-diphenylisonicotinoyl) -4- [1- (2-methylbutanoyl) piperidin-4-yl] piperazine
MS APCI (+): 511.4 [M + H] ⁺ , 533.4 [M + Na] ⁺ .
Example 529: 1- [1- (4-chlorobenzoyl) piperidin-4-yl] -4- (2,6-diphenylisonicotinoyl) piperazine
MS APCI (+): 565.3 [M + H] ⁺ , 587.3 [M + Na] ⁺ .
Example 530: 1- (2,6-diphenylisonicotinoyl) -4- {1-[(1-methyl-1H-imidazol-4-yl) carbonyl] piperidin-4-yl} piperazine
MS APCI (+): 535.4 [M + H] ⁺ , 557.3 [M + Na] ⁺ .
Example 531: 4- (3- {4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} -3-oxopropyl) phenol
MS APCI (+): 575.4 [M + H] ⁺ , 597.4 [M + Na] ⁺ .
MS APCI (−): 573.4 [MH] ^- .
Example 532: 5-amino-2-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) phenol
MS APCI (+): 562.4 [M + H] ⁺ , 584.4 [M + Na] ⁺ .
MS APCI (−): 560.4 [MH] ^- .

Example 533: 1- (9-anthrylcarbonyl) -4- [1- (2-thienylcarbonyl) piperidin-4-yl] piperazine
The reaction was carried out substantially in the same manner as in Example 142 except that 2-thienoyl chloride was used instead of 4-morpholinylcarbonyl chloride to obtain the title compound (33 mg, quant.) As a colorless amorphous.
MS APCI (+): 484.2 [M + H] ⁺ .
Example 534: methyl (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine -2-yl} phenyl) carbamate
4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane) phenyl acetate instead of 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2 Except for using -yl) aniline, a reaction substantially similar to that of Example 200 was performed to give 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] Piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridin-2-yl} aniline (268 mg, 0.451 mmol, 91%) was obtained as a yellow solid.
4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl obtained by the above operation To a solution of pyridin-2-yl} aniline (130 mg, 0.219 mmol) and triethylamine (37 μl, 0.263 mmol) in chloroform (containing amylene) (3.0 ml) was added methyl chloroformate (20 μl, 0.263 mmol) at 0 ° C. Thereafter, the mixture was warmed to room temperature and stirred for 2 hours. The reaction mixture was poured into 1M aqueous sodium hydroxide solution and extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated. The obtained residue was purified by silica gel column chromatography (methanol / chloroform) to obtain the title compound (98 mg, 0.15 mmol, 68%) as a pale yellow amorphous.
MS APCI (+): 653.3 [M + H] ⁺ .

Example 535: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2,6-bis (4-methylphenyl) pyridin-4-yl] Carbonyl} piperazine
MS ESI / APCI Dual (+): 608.4 [M + H] ⁺ .
Example 536: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2,6-bis (4-methoxyphenyl) pyridin-4-yl] Carbonyl} piperazine
MS ESI / APCI Dual (+): 640.3 [M + H] ⁺ , 662.2 [M + Na] ⁺ .
Example 537: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2,6-bis (3-chlorophenyl) pyridin-4-yl] carbonyl } Piperazine
MS ESI / APCI Dual (+): 648.3 [M + H] ⁺ .
Example 538: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2,6-bis (4-chlorophenyl) pyridin-4-yl] carbonyl } Piperazine
MS ESI / APCI Dual (+): 648.3 [M + H] ⁺ .

Example 539: 1-acetyl-4-{[4- (4-{[2,6-bis (4-methylphenyl) pyridin-4-yl] carbonyl} piperazin-1-yl) piperidin-1-yl] Carbonyl} piperazine
MS ESI / APCI Dual (+): 609.4 [M + H] ⁺ .
Example 540: 3- [4-({4- [1- (phenylcarbonyl) piperidin-4-yl] piperazin-1-yl} carbonyl) quinolin-2-yl] benzoic acid
MS ESI / APCI Dual (+): 549.4 [M + H] ⁺ .
Example 541: 4- [4-({4- [1- (phenylcarbonyl) piperidin-4-yl] piperazin-1-yl} carbonyl) quinolin-2-yl] benzoic acid
MS ESI (+): 549.3 [M + H] ⁺ .
Example 542: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,3-benzoxazol-2 (3H) -one
MS ESI / APCI Dual (+): 637.3 [M + H] ⁺ .
Example 543: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,3-Dihydro-2H-indol-2-one
MS ESI / APCI Dual (+): 635.4 [M + H] ⁺ .

Example 544: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2,3-Dihydro-1H-isoindol-1-one
MS ESI / APCI Dual (+): 635.4 [M + H] ⁺ .
Example 545: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2,3-Dihydro-1H-isoindol-1-one
MS ESI / APCI Dual (+): 635.4 [M + H] ⁺ .
Example 546: 2- (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} phenyl) -N-methylacetamide
MS ESI / APCI Dual (+): 651.4 [M + H] ⁺ .
Example 547: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2,3-Dimethyl-1H-indole
MS ESI / APCI Dual (+): 647.4 [M + H] ⁺ .

Example 548: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} Quinoline-2 (1H) -one
MS ESI / APCI Dual (+): 647.4 [M + H] ⁺ .
Example 549: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -3-Methyl-1H-indole
MS ESI / APCI Dual (+): 633.4 [M + H] ⁺ .
Example 550: 3- (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} phenyl) propan-1-ol
MS ESI / APCI Dual (+): 638.4 [M + H] ⁺ .
Example 551: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (4-fluorophenyl) -6-phenylpyridin-4-yl ] Carbonyl} piperazine 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6-phenylisonicotinoyl) obtained in Reference Example 39 Using piperazine as a starting material, substantially the same reaction as in Example 200 was performed using the corresponding reagent to give the title compound.
MS ESI / APCI Dual (+): 598.4 [M + H] ⁺ .
Reaction substantially similar to Example 551 was implemented using the corresponding reagent, and the compound of Examples 552-567 was obtained.

Example 552: 4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl-2,4'- Bipyridine
MS ESI / APCI Dual (+): 581.4 [M + H] ⁺ .
MS ESI / APCI Dual (−): 615.4 [M + Cl] ^- .
Example 553: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (3-fluorophenyl) -6-phenylpyridin-4-yl ] Carbonyl} piperazine
MS ESI / APCI Dual (+): 598.4 [M + H] ⁺ .
MS ESI / APCI Dual (−): 632.4 [M + Cl] ^- .
Example 554: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2-Methyl-1H-indole-3-carbonitrile
MS ESI / APCI Dual (+): 658.5 [M + H] ⁺ .
Example 555: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,2,3-Trimethyl-1H-indole
MS ESI / APCI Dual (+): 661.4 [M + H] ⁺ .
Example 556: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,2-Dimethyl-1H-indole-3-carbonitrile
MS ESI / APCI Dual (+): 672.5 [M + H] ⁺ .
Example 557: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -3-Ethyl-2-methyl-1H-indole
MS ESI / APCI Dual (+): 661.4 [M + H] ⁺ .

Example 558: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -3-Ethyl-1,2-dimethyl-1H-indole
MS ESI / APCI Dual (+): 675.5 [M + H] ⁺ .
Example 559: 1- (5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} -2-methyl-1H-indol-3-yl) ethanone
MS ESI / APCI Dual (+): 675.4 [M + H] ⁺ .

Example 560: 1- (5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} -1,2-dimethyl-1H-indol-3-yl) ethanone
MS ESI / APCI Dual (+): 689.5 [M + H] ⁺ .
Example 561: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1-methyl-1H-indole-3-carbonitrile
MS ESI / APCI Dual (+): 658.4 [M + H] ⁺ .
Example 562: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1- (phenylsulfonyl) -1H-indole
MS ESI / APCI Dual (+): 759.3 [M + H] ⁺ .
Example 563: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1-Methyl-1H-indole
MS ESI / APCI Dual (+): 633.5 [M + H] ⁺ .
Example 564: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2- (methoxymethyl) -3-methyl-1H-indole
MS ESI / APCI Dual (+): 677.5 [M + H] ⁺ .
Example 565: 1- [5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} -3-methyl-1- (phenylsulfonyl) -1H-indol-2-yl] -N, N-dimethylmethanamine
MS ESI / APCI Dual (+): 830.3 [M + H] ⁺ .

Example 566: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,2-Dimethyl-1H-indole
MS ESI / APCI Dual (+): 647.5 [M + H] ⁺ .
Example 567: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,3-Dimethyl-1H-indole
MS ESI / APCI Dual (+): 647.5 [M + H] ⁺ .
Example 568: 4-{[4- (4-{[2- (2,3-dimethyl-1H-indol-5-yl) -6-phenylpyridin-4-yl] carbonyl} piperazin-1-yl) Piperidin-1-yl] carbonyl} piperidine-1-carboxylate methyl
Examples from methyl 4-{[4- (4-[(2-chloro-6-phenylpyridin-4-yl) carbonyl] piperazin-1-yl) piperidin-1-yl] carbonyl} piperidine-1-carboxylate A reaction substantially similar to 200 was performed using the corresponding reagents to give the title compound.
MS ESI / APCI Dual (+): 663.4 [M + H] ⁺ .
Example 569: 5- {4-[(4- {1-[(4-acetylpiperazin-1-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1-Methyl-1H-indole
Using 1- {1-[(4-acetylpiperazin-1-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6-phenylisonicotinoyl) piperazine as a raw material, substantially the same as in Example 200 A similar reaction was carried out using the corresponding reagents to give the title compound.
MS ESI / APCI Dual (+): 634.4 [M + H] ⁺ .

Example 570: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (4-methylphenyl) -6-phenylpyridin-4-yl ] Carbonyl} piperazine 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6- (4-methylphenyl) obtained in Reference Example 40 ) Isonicotinoyl) piperazine was used as a starting material, and substantially the same reaction as in Example 200 was performed using the corresponding reagent to give the title compound.
MS ESI / APCI Dual (+): 594.4 [M + H] ⁺ .
Reaction substantially similar to Example 570 was implemented using the corresponding reagent, and the compound of Examples 571-580 was obtained.
Example 571: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (4-ethylphenyl) -6- (4-methylphenyl) Pyridin-4-yl] carbonyl} piperazine
MS ESI / APCI Dual (+): 622.5 [M + H] ⁺ , 644.4 [M + Na] ⁺ .
Example 572: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (4-methoxyphenyl) -6- (4-methylphenyl) Pyridin-4-yl] carbonyl} piperazine
MS ESI / APCI Dual (+): 624.4 [M + H] ⁺ , 646.5 [M + Na] ⁺ .
MS ESI / APCI Dual (−): 658.5 [M + Cl] ^- .
Example 573: 4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methylphenyl)- 2,4'-bipyridine
MS ESI / APCI Dual (+): 595.4 [M + H] ⁺ .
Example 574: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (3-fluorophenyl) -6- (4-methylphenyl) Pyridin-4-yl] carbonyl} piperazine
MS ESI / APCI Dual (+): 612.4 [M + H] ⁺ .

Example 575: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (4-fluorophenyl) -6- (4-methylphenyl) Pyridin-4-yl] carbonyl} piperazine
MS ESI / APCI Dual (+): 612.4 [M + H] ⁺ .
Example 576: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4-{[2- (1-methyl-1H-pyrazol-4-yl) -6 -(4-Methylphenyl) pyridin-4-yl] carbonyl} piperazine
MS ESI / APCI Dual (+): 598.4 [M + H] ⁺ .
Example 577: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -1- (phenylsulfonyl) -1H-indole
MS ESI / APCI Dual (+): 773.4 [M + H] ⁺ .
Example 578: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} benzonitrile
MS ESI / APCI Dual (+): 619.4 [M + H] ⁺ .
Example 579: 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} benzaldehyde
MS ESI / APCI Dual (+): 622.3 [M + H] ⁺ .

Example 580: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} quinoline
MS ESI / APCI Dual (+): 645.5 [M + H] ⁺ .
Example 581: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-cyclopent-1- 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2) obtained in En-1-ylpyridin-2-yl} -1H-indole Reference Example 41 Using -chloro-6- (1H-indol-5-yl) isonicotinoyl) piperazine as a starting material, substantially the same reaction as in Example 200 was carried out using the corresponding reagent to give the title compound.
MS ESI / APCI Dual (+): 609.4 [M + H] ⁺ , 631.3 [M + Na] ⁺ .
Reaction substantially similar to Example 581 was implemented using the corresponding reagent, and the compound of Examples 582-600 was obtained.
Example 582: 4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (1H-indole-5- Yl) -2,4'-bipyridine
MS ESI / APCI Dual (+): 620.4 [M + H] ⁺ , 642.4 [M + Na] ⁺ .
Example 583: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-cyclohex-1- En-1-ylpyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 623.4 [M + H] ⁺ .
Example 584: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (1H-pyrrole -2-yl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 608.4 [M + H] ⁺ , 630.5 [M + Na] ⁺ .
Example 585: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-fluoro Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 637.4 [M + H] ⁺ .

Example 586: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-chlorophenyl ) Pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 653.3 [M + H] ⁺ .
Example 587: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-chlorophenyl ) Pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 653.3 [M + H] ⁺ .
Example 588: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-fluoro Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 637.3 [M + H] ⁺ .
Example 589: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 633.4 [M + H] ⁺ .
Example 590: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methoxy Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 649.4 [M + H] ⁺ .

Example 591: 1- (3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- ( 1H-Indol-5-yl) pyridin-2-yl} phenyl) ethanone
MS ESI / APCI Dual (+): 661.4 [M + H] ⁺ .
Example 592: 1- (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- ( 1H-Indol-5-yl) pyridin-2-yl} phenyl) ethanone
MS ESI / APCI Dual (+): 661.4 [M + H] ⁺ .
Example 593: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- [3- ( Trifluoromethyl) phenyl] pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 687.3 [M + H] ⁺ .

Example 594: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- [4- ( Trifluoromethyl) phenyl] pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 687.2 [M + H] ⁺ .
Example 595: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- [3- ( Trifluoromethoxy) phenyl] pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 703.3 [M + H] ⁺ .
Example 596: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- [4- ( Trifluoromethoxy) phenyl] pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 703.3 [M + H] ⁺ .
Example 597: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-fluoro -4-methoxyphenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 667.3 [M + H] ⁺ .
Example 598: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3,5 -Difluorophenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 655.2 [M + H] ⁺ .

Example 599: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3,4 -Dimethoxyphenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 679.3 [M + H] ⁺ .
Example 600: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-fluoro -4-methylphenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 651.3 [M + H] ⁺ .
Example 601: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-fluoro Phenyl) pyridin-2-yl} -2,3-dimethyl-1H-indole
1- {1-[(1-acetylpiperidine-4) obtained in the same manner as in Reference Example 41 using 2-chloro-6- (2,3-dimethyl-1H-indol-5-yl) isonicotinic acid. -Yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6- (2,3-dimethyl-1H-indol-5-yl) isonicotinoyl) piperazine as a starting material, substantially the same as Example 200 A similar reaction was carried out using the corresponding reagents to give the title compound.
MS ESI / APCI Dual (+): 655.5 [M + H] ⁺ .

A reaction substantially similar to that of Example 601 was carried out using the corresponding reagents to give the compounds of Examples 602 to 605.
Example 602: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-methyl Phenyl) pyridin-2-yl} -2,3-dimethyl-1H-indole
MS ESI / APCI Dual (+): 661.3 [M + H] ⁺ .
Example 603: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-chlorophenyl ) Pyridin-2-yl} -2,3-dimethyl-1H-indole
MS ESI / APCI Dual (+): 681.3 [M + H] ⁺ .
Example 604: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -2,3-dimethyl-1H-indole
MS ESI / APCI Dual (+): 661.4 [M + H] ⁺ .

Example 605: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-fluoro -4-methylphenyl) pyridin-2-yl} -2,3-dimethyl-1H-indole
MS ESI / APCI Dual (+): 679.2 [M + H] ⁺ , 701.4 [M + Na] ⁺ .
MS ESI / APCI Dual (−): 677.3 [M + Cl] ^- .
Example 606: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -1H-indole
1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidine obtained in the same manner as in Reference Example 41 using 2-chloro-6- (1H-indol-6-yl) isonicotinic acid -4-yl} -4- (2-chloro-6- (1H-indol-6-yl) isonicotinoyl) piperazine was used as a raw material, and a reaction substantially similar to that in Example 200 was performed using the corresponding reagents. Performed to give the title compound.
MS ESI / APCI Dual (+): 633.3 [M + H] ⁺ .
Reaction substantially similar to Example 606 was implemented using the corresponding reagent, and the compounds of Examples 607 to 609 were obtained.
Example 607: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methoxy Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 649.3 [M + H] ⁺ .

Example 608: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-ethyl Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 647.3 [M + H] ⁺ .
Example 609: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-ethoxy Phenyl) pyridin-2-yl} -1H-indole
MS ESI / APCI Dual (+): 663.3 [M + H] ⁺ .
Example 610: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2,3-Dimethyl-1H-indole
1- {1-[(1-acetylpiperidine-4) obtained in the same manner as in Reference Example 41 using 2-chloro-6- (2,3-dimethyl-1H-indol-6-yl) isonicotinic acid. -Yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6- (2,3-dimethyl-1H-indol-6-yl) isonicotinoyl) piperazine as a starting material, substantially the same as Example 200 A similar reaction was carried out using the corresponding reagents to give the title compound.
MS ESI / APCI Dual (+): 647.2 [M + H] ⁺ .

Example 611 4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (1-methyl-1H- Indol-5-yl) -2,4'-bipyridine
1- {1-[(1-acetylpiperidin-4-yl) obtained in the same manner as in Reference Example 41 using 2-chloro-6- (1-methyl-1H-indol-5-yl) isonicotinic acid ) Carbonyl] piperidin-4-yl} -4- (2-chloro-6- (1-methyl-1H-indol-5-yl) isonicotinoyl) piperazine as a starting material, substantially the same reaction as in Example 200 Was performed using the corresponding reagents to give the title compound.
MS ESI / APCI Dual (+): 634.4 [M + H] ⁺ .
Reaction substantially similar to Example 611 was implemented using the corresponding reagent, and the compound of Examples 612-616 was obtained.
Example 612: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-fluoro Phenyl) pyridin-2-yl} -1-methyl-1H-indole
MS ESI / APCI Dual (+): 651.4 [M + H] ⁺ .
Example 613: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-fluoro Phenyl) pyridin-2-yl} -1-methyl-1H-indole
MS ESI / APCI Dual (+): 651.4 [M + H] ⁺ .
MS ESI / APCI Dual (−): 685.5 [M + Cl] ^- .
Example 614: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-chlorophenyl ) Pyridin-2-yl} -1-methyl-1H-indole
MS ESI / APCI Dual (+): 667.4 [M + H] ⁺ .

Example 615: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-chlorophenyl ) Pyridin-2-yl} -1-methyl-1H-indole
MS ESI / APCI Dual (+): 667.4 [M + H] ⁺ .
Example 616: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (3-methyl Phenyl) pyridin-2-yl} -1-methyl-1H-indole
MS ESI / APCI Dual (+): 647.4 [M + H] ⁺ , 669.0 [M + Na] ⁺ .
Example 617: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -2-Methyl-1H-indole
1- {1-[(1-acetylpiperidin-4-yl) obtained in the same manner as in Reference Example 41 using 2-chloro-6- (2-methyl-1H-indol-5-yl) isonicotinic acid ) Carbonyl] piperidin-4-yl} -4- (2-chloro-6- (2-methyl-1H-indol-5-yl) isonicotinoyl) piperazine as a starting material, substantially the same reaction as in Example 200 Was performed using the corresponding reagents to give the title compound.
MS ESI / APCI Dual (+): 633.3 [M + H] ⁺ .
Example 618: 6- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1H-indazole
1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidine obtained in the same manner as in Reference Example 41 using 2-chloro-6- (1H-indazol-6-yl) isonicotinic acid -4-yl} -4- (2-chloro-6- (1H-indazol-6-yl) isonicotinoyl) piperazine was used as a raw material, and a reaction substantially similar to that in Example 200 was performed using the corresponding reagents. Performed to give the title compound.
MS ESI / APCI Dual (+): 620.4 [M + H] ⁺ .

Example 619: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-pyrrolidine-1- 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6) obtained in Reference Example 41 of ylpyridin-2-yl} -1H-indole A solution of-(1H-indol-5-yl) isonicotinoyl) piperazine (100 mg, 0.173 mmol) in pyrrolidine (4.0 ml) was heated to reflux for 7 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (methanol / chloroform) to obtain the title compound (84 mg, 0.137 mmol, 79%) as a light brown amorphous.
MS ESI / APCI Dual (+): 612.5 [M + H] ⁺ , 634.4 [M + Na] ⁺ .
Example 620: 2-methyl-5- [6-phenyl-4-({4- [1- (phenylcarbonyl) piperidin-4-yl] piperazin-1-yl} carbonyl) pyridin-2-yl] -1H -Indole-3-carbonitrile 1- (1-benzoylpiperidin-4-yl) piperazine (77 mg, 0.282 mmol), 2- (3-cyano-2-methyl-1H-indole-5 obtained in Reference Example 8 EDC · HCl (81 mg, 0.424 mmol) was added to a chloroform (2 mL) solution of -yl) -6-phenylpyridine-4-carboxylic acid (100 mg, 0.282 mmol) and HOBt · H 2 O (57 mg, 0.424 mmol) at room temperature. Stir overnight. The reaction solution was washed with saturated brine and dried over anhydrous magnesium sulfate. The desiccant was filtered off and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol / chloroform), NH-type silica gel column chromatography (methanol / chloroform), and silica gel column chromatography (ethyl acetate) to give the title compound. (100 mg, 0.164 mmol, 58%) was obtained as a colorless powder.
MS ESI / APCI Dual (+): 609.5 [M + H] ⁺ .

Reaction substantially similar to Example 620 was implemented using the corresponding reagent, and the compounds of Examples 621 to 622 were obtained.
Example 621 5- [4-({4- [1- (cyclopentylcarbonyl) piperidin-4-yl] piperazin-1-yl} carbonyl) -6-phenylpyridin-2-yl] -2-methyl-1H -Indole-3-carbonitrile
MS ESI / APCI Dual (+): 601.4 [M + H] ⁺ .
Example 622: 4- (4-{[2- (3-cyano-2-methyl-1H-indol-5-yl) -6-phenylpyridin-4-yl] carbonyl} piperazin-1-yl) piperidine- 1-carboxylic acid 1-methylethyl
MS ESI / APCI Dual (+): 591.4 [M + H] ⁺ .
Example 623: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-cyclopentylpyridine-2 -Il} -1H-indole 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl obtained in Example 581 ) Carbonyl] -6-cyclopent-1-en-1-ylpyridin-2-yl} -1H-indole (137 mg, 0.225 mmol) in methanol (5.0 ml) was added palladium-carbon (10%) (15 mg) The system was replaced with hydrogen and stirred at room temperature for 20 hours. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure and purified by NH silica gel column chromatography (methanol / chloroform) to give the title compound (96 mg, 0.157 mmol, 70%) as a pale yellow amorphous product.
MS ESI / APCI Dual (+): 611.4 [M + H] ⁺ , 633.5 [M + Na] ⁺ .

Example 624: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-cyclohexylpyridine-2 -Il} -1H-indole 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl obtained in Example 583 ) Carbonyl] -6-cyclohex-1-en-1-ylpyridin-2-yl} -1H-indole was used to give the title compound in the same manner as in Example 623.
MS ESI / APCI Dual (+): 625.4 [M + H] ⁺ .
MS ESI / APCI Dual (−): 623.3 [MH] ^- .
Example 625: 1- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2-chloro-6-phenyl) obtained in Reference Example 39 Isonicotinoyl) piperazine (150 mg, 0.279 mmol), 2-pyrrolidinone (10 mg, 0.12 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (20 mg, 0.033 mmol), cesium carbonate (127 mg) , 0.4 mmol) of 1,4-dioxane (1 ml) was stirred at 100 ° C. for 12 hours under an argon atmosphere. The reaction solution was filtered through Celite, and the resulting residue was purified by NH silica gel column chromatography (methanol / chloroform) to obtain the title compound (79 mg, 0.135 mmol, 48%) as a colorless amorphous.
MS ESI / APCI Dual (+): 587.4 [M + H] ⁺ .
A reaction substantially similar to that of Example 625 was carried out using the corresponding reagents to give the compounds of Examples 626 to 629.
Example 626: 1- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} azetidin-2-one
MS ESI / APCI Dual (+): 573.4 [M + H] ⁺ .

Example 627: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1,3-oxazolidine-2-one
MS ESI / APCI Dual (+): 589.4 [M + H] ⁺ .
Example 628: 1- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -3-Methylimidazolidin-2-one
MS ESI / APCI Dual (+): 602.4 [M + H] ⁺ .
Example 629: N- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} acetamide
MS ESI / APCI Dual (+): 561.4 [M + H] ⁺ , 583.4 [M + Na] ⁺ .
MS ESI / APCI Dual (−): 559.5 [MH] ^- .

Example 630: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -1-methyl-1H-indole
5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] obtained in Example 589 was suspended in 60% sodium hydride oily (13 mg) dimethylformamide (3 mL) suspension. ] Piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methylphenyl) pyridin-2-yl} -1H-indole (180 mg, 0.284 mmol) in dimethylformamide (2 mL) was added, After stirring at room temperature for 10 minutes, methyl iodide (0.019 mL, 0.313 mmol) was added, and the mixture was stirred at room temperature for 1 hour. The reaction solution was diluted with chloroform, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered off and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol / chloroform) to give the title compound (37 mg, 0.057 mmol, 20%) as a pale yellow amorphous product.
MS ESI / APCI Dual (+): 647.3 [M + H] ⁺ .
Reaction substantially similar to Example 630 was implemented using the corresponding reagent, and the compound of Examples 631-634 was obtained.
Example 631: 4- (4-{[2- (3-cyano-1,2-dimethyl-1H-indol-5-yl) -6-phenylpyridin-4-yl] carbonyl} piperazin-1-yl) Piperidine-1-carboxylic acid 1-methylethyl
MS ESI / APCI Dual (+): 605.4 [M + H] ⁺ .

Example 632: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1-Methyl-1H-indole
MS ESI / APCI Dual (+): 633.4 [M + H] ⁺ .
Example 633: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -1-methyl-1H-indole
MS ESI / APCI Dual (+): 647.5 [M + H] ⁺ .
Example 634: 5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1-ethyl-1H-indole
MS ESI / APCI Dual (+): 647.5 [M + H] ⁺ .

Example 635: 1- (4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- ( 4-Methylphenyl) pyridin-2-yl} phenyl) -N, N-dimethylmethanamine 4- {4-[(4- {1-[(1-acetylpiperidin-4-yl) obtained in Example 579 ) Carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methylphenyl) pyridin-2-yl} benzaldehyde (187 mg, 0.30 mmol) in chloroform (5 mL) in 33% dimethylamine -An ethanol solution (0.054 mL) and sodium triacetoxyborohydride (127 mg, 0.60 mmol) were added, and the mixture was stirred overnight at room temperature. To the reaction system was added 1M aqueous sodium hydroxide solution, and the mixture was extracted with chloroform. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The desiccant was filtered off and concentrated under reduced pressure. The residue was purified by NH silica gel chromatography (chloroform) to obtain the title compound (98 mg, 0.15 mmol, 50%) as a colorless amorphous.
MS ESI / APCI Dual (+): 651.5 [M + H] ⁺ .
Example 636: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6- (4-methyl Phenyl) pyridin-2-yl} -1H-indole 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} obtained in Example 577 Piperazin-1-yl) carbonyl] -6- (4-methylphenyl) pyridin-2-yl} -1- (phenylsulfonyl) -1H-indole (492 mg, 0.636 mmol) in tetrahydrofuran (15 mL) was added 1M tetrabutyl. Ammonium fluoride-tetrahydrofuran solution (0.64 mL) was added, and the mixture was heated to reflux for 3 hours. Further, 1M tetrabutylammonium fluoride-tetrahydrofuran solution (0.64 mL) was added, and the mixture was heated to reflux for 1.5 hours. After allowing to cool, the solvent was distilled off, and the residue was poured into water and extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and the desiccant was filtered off and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (methanol / chloroform) and NH silica gel column chromatography (methanol / chloroform) to obtain the title compound (156 mg, 0.247 mmol, 39%) as a yellow powder.
MS ESI / APCI Dual (+): 633.4 [M + H] ⁺ .
Reaction substantially similar to Example 636 was implemented using the corresponding reagent, and the compound of Examples 637-638 was obtained.
Example 637: 3- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridine-2 -Il} -1H-Indole
MS ESI / APCI Dual (+): 619.4 [M + H] ⁺ .
Example 638: 1- (5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl Pyridin-2-yl} -3-methyl-1H-indol-2-yl) -N, N-dimethylmethanamine
MS ESI / APCI Dual (+): 690.5 [M + H] ⁺ .

Example 639: 2- (5- {4-[(4- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenyl 1- {1-[(1-Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- obtained in Reference Example 38 of pyridin-2-yl} -1H-indol-1-yl) ethanol (2-Chloro-6-phenylisonicotinoyl) piperazine (100 mg, 0.186 mmol) and 1- (2-{[tert-butyl (dimethyl) silyl] oxy} ethyl) -5- (4,4,5,5 5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-indole (236 mg, 0.588 mmol) in the same manner as in Example 200, 5- {4-[(4- {1-[(1- Acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} piperazin-1-yl) carbonyl] -6-phenylpyridin-2-yl} -1- (2-{[tert-butyl (dimethyl) silyl] oxy } Ethyl) -1H-indole (95 mg) was obtained. A 1M tetrabutylammonium fluoride-tetrahydrofuran solution (0.35 mL) was added to a tetrahydrofuran solution (3 mL) of the obtained silyl compound (90 mg), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with chloroform, washed with water and saturated brine, and dried over anhydrous magnesium sulfate. The desiccant was filtered off, concentrated under reduced pressure, and purified by silica gel column chromatography (methanol / chloroform) to give the title compound (45 mg, 0.068 mmol, 37%, 2 steps) as a colorless amorphous.
MS ESI / APCI Dual (+): 663.4 [M + H] ⁺ .
Example 640 4- [4-({2-[(ethylcarbamoyl) amino] quinolin-4-yl} carbonyl) piperazin-1-yl] piperidine-1-carboxylic acid 1-methylethyl
4- {4-[(2-chloroquinolin-4-yl) carbonyl] piperazin-1-yl} piperidine-1-carboxylic acid 1-methylethyl (140 mg, 0.40 mmol), ethylurea (35 mg, 0.40 mmol), acetic acid Palladium (3 mg, 0.012 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (14 mg, 0.024 mmol), sodium t-butoxy (54 mg, 0.56 mmol), water (0.01 mL, 0.56 mmol) ) Was stirred at 100 ° C. for 5 hours under a nitrogen atmosphere. After allowing to cool, the mixture was concentrated under reduced pressure, and the residue was purified by NH silica gel column chromatography (ethyl acetate) to give the title compound (47 mg, 0.095 mmol, 24%) as a pale yellow amorphous product.
MS ESI / APCI Dual (+): 497.3 [M + H] ⁺ .

Example 641: 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine hydrochloride obtained in Example 2 1- {1-[(1-acetylpiperidin-4-yl) carbonyl] piperidin-4-yl} -4- (2,6-diphenylisonicotinoyl) piperazine (5.21 g, 8.99 mmol) in ethyl acetate ( 90 ml), 4M hydrochloric acid-ethyl acetate (2.2 ml, 8.8 mmol) was added dropwise at room temperature and stirred for 3 days. Ether (30 ml) was added to the reaction mixture, and suction filtration was performed to obtain the title compound (4.56 g, 7.4 mmol, 84%) as a colorless solid.
¹ H-NMR (600 MHz, DMSO-d ₆ ) δ 1.20-1.36 (m, 1 H), 1.39-1.53 (m, 2 H), 1.54-1.66 (m, 3 H), 1.95 (s, 3 H ), 2.06-2.23 (m, 2 H), 2.44-2.62 (m, 2 H), 2.83-2.92 (m, 1 H), 2.95-3.24 (m, 4 H), 3.27-3.38 (m, 2 H ), 3.39-3.50 (m, 2 H), 3.52-3.62 (m, 1 H), 3.66-3.81 (m, 2 H), 4.09-4.21 (m, 1 H), 4.26-4.35 (m, 1 H ), 4.46-4.56 (m, 1 H), 4.57-4.67 (m, 1 H), 7.44-7.57 (m, 6 H), 7.96 (s, 2 H), 8.18-8.26 (m, 4 H), 11.52-11.70 (m, 1 H).
Example 642: 1-acetyl-4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperazine maleate Obtained in Example 55 1-acetyl-4-({4- [4- (2,6-diphenylisonicotinoyl) piperazin-1-yl] piperidin-1-yl} carbonyl) piperazine (900 mg, 1.55 mmol) in ethyl acetate ( 20 ml), 0.1M maleic acid ethyl acetate solution (15 ml) was added dropwise at room temperature and stirred overnight. The reaction solution was subjected to suction filtration to obtain the title compound (950 mg, 1.36 mmol, 88%) as a colorless solid.
¹ H-NMR (600 MHz, DMSO-d ₆ ) δ 1.44-1.55 (m, 2 H), 1.87-1.95 (m, 2 H), 1.97 (s, 3 H), 2.70-2.79 (m, 2 H ), 2.95-3.27 (m, 11H), 3.34-3.43 (m, 4 H), 3.47-3.59 (m, 2 H), 3.62-3.70 (m, 2 H), 6.06 (s, 2 H), 7.45 -7.56 (m, 6 H), 7.93 (s, 2 H), 8.17-8.26 (m, 4 H).

The compounds of the present invention obtained in the above examples are shown in Table 1.

Test example 1
The ACC inhibitory action of the compound of the present invention or a salt thereof was measured by the following method.

(1) Preparation of human ACC enzyme Human ACC was purified from human liver cytosol (KAC Corporation). After 9.5 mL of cryopreserved human liver cytosol was thawed on ice, 1.67 g of ammonium sulfate was added and stirred overnight at 4 ° C. The ammonium sulfate solution was centrifuged at 18,000 × g for 15 minutes, and the resulting precipitate was dissolved in 5 mL of buffer A (50 mM MOPS (pH 7.5), 250 mM sucrose, 2 mM EDTA, 2 mM DTT, 5% glycerol). . The obtained lysate was desalted using a PD-10 column (GE Healthcare Bioscience) and flowed at a flow rate of 2 mL onto a Resource Q column (GE Healthcare Bioscience) previously equilibrated with 60 mL of Buffer A. / Min. Passed through. After washing with 10 mL of buffer A, buffer B (50 mM MOPS (pH 7.5), 500 mM sodium chloride, 2 mM EDTA, 2 mM DTT, 5% glycerol) was added to buffer A at 20%, 50%, and 100%. The human ACC enzyme was obtained from the 50% concentration eluate. The obtained human ACC enzyme was stored frozen at -80 ° C.

(2) Measurement of ACC inhibitory activity The test compound (the test compound was used as a free form or a free form made into a salt according to the method of Examples 535 and 536) was adjusted to 500 μg / mL with 10% dimethyl sulfoxide. It was dissolved in. Ten dilution series with an initial concentration of 500 μg / mL were prepared at a common ratio of 3, and 3 μL of each solution was added to each well of a 384-well assay plate (Matrix). Next, the ACC obtained in (1) above was converted into an enzyme reaction buffer (90.9 mM Tris-acetic acid (pH 7.5), 1.98 μM β-mercaptoethanol, 7.5 mM magnesium acetate, 12 mM magnesium sulfate, 15 mM citric acid. After diluting sodium (1.5 mg / mL Fatty acid free BSA) to a concentration of 30 μg / mL, 20 μL was added to each well and allowed to react at 37 ° C. for 30 minutes. Next, 7 μL of a substrate solution (9.09 mM ATP, 78 mM NaHCO 3, 35.1 μM [14C] -acetyl-CoA (110 mCi / mmol), 70.2 μM acetyl-CoA) was added to each well at 37 ° C. for 60 minutes. Reacted. Immediately after that, 20 μL each of carnitine reaction solution (25 mM carnitine, 0.47 mU / mL carnitine acetyltransferase (Sigma)) was added to each well, reacted at 37 ° C. for 45 minutes, and the remaining substrate ([14C] − Acetyl-CoA and acetyl-CoA) were fully converted to acetylcarnitine. 40 μL of the reaction solution thus obtained was transferred to a 96-well multiscreen DV (Millipore), mixed with 90 μL of 50% / vol cation exchange resin (Nippon Bio-Rad Laboratories), reacted at room temperature for 30 minutes, and acetylcarnitine was added. Adsorbed sufficiently on the cation exchange resin. Thereafter, the reaction solution is sucked with a multi-screen vacuum manifold (Millipore), [14C] -malonyl-CoA and malonyl-CoA that are not adsorbed on the cation exchange resin are transferred to an isoplate (Corning), and 120 μL of scintillator is added. After mixing well, the radioactivity was measured with MicroBeta TRILUX (Perkin Elmer) (test compound addition group). In addition, 3 μL of a solution obtained by diluting only dimethyl sulfoxide with distilled water without adding the test compound was added to each well, and the same reaction as described above was performed (test compound non-added group). Further, 3 μL of 1 mg / mL avidin was added to each well without adding the test compound, and a reaction similar to the above was performed (control group). The ACC inhibitory activity of each compound was calculated from the following formula, and the concentration at which 50% inhibition was obtained (IC50 value) was determined.
Inhibition rate (%) = {1− (radioactivity of test compound added group−radioactivity of control group) ÷
(Radioactivity of test substance non-added group-radioactivity of control group)} × 100
It was confirmed that some of the compounds of the present invention have an inhibitory activity with an IC50 value of 1 μM or less.

  The compounds of the present invention are effective in the treatment and prevention of obesity, hyperlipidemia, diabetes, diabetic complications, hypertension, heart failure, diabetic cardiomyopathy, metabolic syndrome and atherosclerosis.

Claims (4)

Formula (I)

[Where
Y represents CH or N;
R1 and R4 are the same or different,
(1) Aryl which may be substituted (Here, the aryl which may be substituted is
A halogen atom,
・ Hydroxy,
-C2-C7 alkoxycarbonyl which may be substituted with a halogen atom, hydroxy, C1-C6 alkoxy, carboxy, dimethylamino, aryl, and -CONR5R6 (wherein R5 and R6 are the same or different, a hydrogen atom, "halogen C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl, or aryl which may be substituted with a halogen atom or hydroxy, or R5 and R6 are Together with the adjacent nitrogen atom, a “nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” may be formed. C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of:
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Formyl cyano,
A C2-C6 alkanoyl optionally substituted with a halogen atom or hydroxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR7R8 (wherein R7 and R8 are the same or different and are a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl", Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R7 and R8 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted with aryl, -CONR9R10 (wherein R9 and R10 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or aryl which may be substituted with hydroxy, or R9 and R10 are adjacent nitrogen atoms and Together, they may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” and C1-. Amino optionally substituted by one or more groups selected from the group consisting of C6 alkylsulfonyl, and C1-C6 alkyl Aryl optionally substituted with one or more groups selected from the group consisting of rusulfonyl. ),
(2) Formula (II)

(In the formula, CycB is a 4- to 8-membered ring structure formed with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and sulfur atom. And the CycB is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom, hydroxy, C1-C6 alkoxy, or amino substituted with C1-C6 alkyl,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR11R12 (wherein R11 and R12 are the same or different and are a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl", Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R11 and R12 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR13R14 (wherein R13 and R14 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl Or a C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or an aryl which may be substituted with hydroxy, or R13 and R14 are an adjacent nitrogen atom and Together, they may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” and C1-. Amino optionally substituted with one or more groups selected from the group consisting of C6 alkylsulfonyl, and C1-C6 A saturated hydrocarbon ring, an unsaturated hydrocarbon ring, a saturated heterocyclic ring or an unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of alkylsulfonyl and arylsulfonyl. A condensed ring represented by
(3) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
-C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy; and-It may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy Heteroaryl which may be substituted with one or more groups selected from the group consisting of C2-C6 alkanoyl. ),
(4) C1-C6 alkyl, or saturated or partially unsaturated heterocycle optionally substituted with oxo (5) C1-C6 alkyl optionally substituted with hydroxy (6) C5-C6 cycloalkenyl or C5- C1-C6 alkyl optionally substituted with C6 cycloalkyl (7) C1-C6 alkoxy (8) oxo and -CONR13R14 (wherein R13 and R14 are the same or different and each represents a hydrogen atom or C1-C6 alkyl). An amino optionally substituted with one or more groups selected from the group consisting of:
R2 and R3 are
R 1 and R 2 may form a benzene ring together with adjacent carbon atoms, and R 3 and R 4 may form a benzene ring together with adjacent carbon atoms. ,
m and n each represent 1 or 2,
X represents CO or SO ₂ ;
A is
(1) C1-C10 alkyl which may be substituted (Here, C1-C10 alkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkoxy optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and aryl,
A C3-C15 cycloalkyl optionally substituted with one or more groups selected from the group consisting of hydroxy, oxo, C1-C6 alkyl and C1-C6 alkoxy;
C5-C6 cycloalkenyl,
・ Carboxy,
・ Cyano,
・ Oxo,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR15R16 (wherein R15 and R16 are the same or different and are each a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents an aryl optionally substituted with a halogen atom or hydroxy, or R15 and R16 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR17R18 (wherein R17 and R18 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl Or a C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or an aryl which may be substituted with hydroxy, or R17 and R18 are adjacent nitrogen atoms and Together, it may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”), C1-. Selected from the group consisting of C6 alkylsulfonyl, aryl, arylcarbonyl and heteroarylcarbonyl Amino, optionally substituted with one or more groups,
C1-C6 alkylsulfonyl,
An aryl optionally substituted with one or more groups selected from the group consisting of C1-C6 alkoxy optionally substituted with a halogen atom, hydroxy and aryl,
A heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo,
A C8-C10 partially unsaturated hydrocarbon condensed ring, and an aryloxy optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkanoyl,
C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of ),
(2) C2-C10 alkenyl,
(3) C3-C15 cycloalkyl which may be substituted (Here, C3-C15 cycloalkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
C1-C6 alkoxy,
・ Carboxy,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-C3-C15 cycloalkyl which may be substituted with one or more groups selected from the group consisting of arylcarbonyl and aryl which may be substituted with a halogen atom. ),
(4) A saturated or partially unsaturated heterocyclic ring that may be substituted (here, a saturated or partially unsaturated heterocyclic ring that may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
・ Aryl,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of formyl, halogen atoms and oxo,
Hydroxy, C1-C6 alkoxy and “C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted with aryl, —CONR19R20 (wherein R19 and R20 are the same or different, a hydrogen atom , “C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl”, or aryl optionally substituted with a halogen atom or hydroxy, or R19 and R20 together with the adjacent nitrogen atom forms "a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo". And one or more groups selected from the group consisting of C1-C6 alkylsulfonyl. C1-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of “amino optionally substituted”,
C4-C16 cycloalkylcarbonyl,
An arylcarbonyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
A heteroarylcarbonyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR21R22 (wherein R21 and R22 are the same or different and each is a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R21 and R22 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
A saturated or partially unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl which may be substituted with a halogen atom, and C1-C6 alkylaminosulfonyl. ),
(5) aryl which may be substituted (here, aryl which may be substituted is a halogen atom,
・ Hydroxy,
A C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
A C1-C6 alkoxy which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
・ Carboxy,
・ Cyano,
-C2-C6 alkanoyl optionally substituted with formyl-halogen atom,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of hydroxy, C1-C6 alkoxy and C1-C6 alkanoyloxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR23R24 (wherein R23 and R24 are the same or different and are a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R23 and R24 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR25R26 (wherein R25 and R26 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl Or a C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or a halogen atom or an aryl which may be substituted with hydroxy, or R25 and R26 each represents an adjacent nitrogen atom; Together, they may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo” and C1-. An amino optionally substituted with one or more groups selected from the group consisting of C6 alkylsulfonyl,
・ Nitro,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
Arylcarbonyl,
・ Aryloxy,
Heteroaryl,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo, and at least one selected from the group consisting of C1-C6 alkylsulfonyl Aryl optionally substituted with a group is shown. ),
(6) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and saturated heterocycles,
A C1-C6 alkoxy optionally substituted with a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Nitro,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR27R28 (wherein R27 and R28 are the same or different and are each a hydrogen atom, "C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl"; Alternatively, it represents aryl optionally substituted with a halogen atom or hydroxy, or R27 and R28 together with the adjacent nitrogen atom are selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” A nitrogen-containing saturated heterocycle "which may be substituted with two or more groups".
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR29R30 (wherein R29 and R30 are the same or different and represent a hydrogen atom, a "halogen atom, hydroxy and aryl C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of, or aryl which may be substituted with a halogen atom or hydroxy, or R29 and R30 are adjacent nitrogen atoms and Together, it may form “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”), C1-. C6 alkylsulfonyl, substituted with one or more groups selected from the group consisting of “halogen atom, hydroxy and nitro” An aryl optionally substituted with one or more groups selected from the group consisting of aryl, a saturated heterocyclic ring, and aryloxy optionally substituted with a halogen atom,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups,
-Aryloxy which may be substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups; and-may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl Heteroaryl is shown. ),
(7) a C8-C10 partially unsaturated hydrocarbon condensed ring optionally substituted with one or more groups selected from the group consisting of a halogen atom and oxo;
(8) C1-C6 alkoxy which may be substituted (Here, C1-C6 alkoxy which may be substituted is
-Aryl, or C1-C6 alkoxy which may be substituted with C1-C6 alkoxy which may be substituted with aryl. ),
(9) Aryloxy which may be substituted (Here, aryloxy which may be substituted is
-C1-C6 alkyl which may be substituted with a halogen atom, or aryloxy which may be substituted with C2-C7 alkoxycarbonyl which may be substituted with aryl. ), Or (10) optionally substituted amino (wherein optionally substituted amino is
C1-C6 alkyl which may be substituted with a halogen atom or hydroxy, and amino which may be substituted with one or more groups selected from the group consisting of aryl which may be substituted with halogen atom or hydroxy. )
Indicates. Or a pharmaceutically acceptable salt thereof or a hydrate thereof. Formula (I ′)

[Where
Y ′ represents CH or N;
R1 ′ and R4 ′ are the same or different,
(1) Aryl which may be substituted (Here, the aryl which may be substituted is
A halogen atom,
・ Hydroxy,
A halogen atom, hydroxy, C1-C6 alkoxy, carboxy, C2-C7 alkoxycarbonyl optionally substituted by aryl and -CONR5'R6 '(wherein R5' and R6 'are the same or different, a hydrogen atom, “C1-C6 alkyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl”, or aryl optionally substituted with halogen atoms or hydroxy, or R 5 ′ and R6 ′ together with the adjacent nitrogen atom forms “a nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. A C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of:
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
A C2-C6 alkanoyl optionally substituted with a halogen atom or hydroxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR7'R8 '(wherein R7' and R8 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”, or aryl optionally substituted with a halogen atom or hydroxy, or R7 ′ and R8 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR9'R10 '(wherein R9' and R10 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl "which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl", or aryl which may be substituted with halogen atom or hydroxy, or R9 'and R10' Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. And amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl, and C1-C6 An aryl which may be substituted with one or more groups selected from the group consisting of alkylsulfonyl is shown. ),
(2) Formula (II ′)

(In the formula, CycB ′ is a 4- to 8-membered ring formed together with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and sulfur atom. Shows the structure, and CycB ′ is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted by a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted with a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR11'R12 '(wherein R11' and R12 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R11 ′ and R12 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, —CONR13′R14 ′ (wherein R13 ′ and R14 ′ are the same or different, a hydrogen atom, “halogen” C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of an atom, hydroxy and aryl, or aryl which may be substituted with a halogen atom or hydroxy, or R13 ′ and R14 ′ Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. And amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl, and C1-C6 A saturated hydrocarbon ring, an unsaturated hydrocarbon ring, a saturated heterocyclic ring or an unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of alkylsulfonyl. A condensed ring represented by
(3) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
-C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy; and-It may be substituted with one or more groups selected from the group consisting of halogen atoms and hydroxy Heteroaryl which may be substituted with one or more groups selected from the group consisting of C2-C6 alkanoyl. ),
(4) C1-C6 alkyl optionally substituted with hydroxy, or (5) C1-C6 alkoxy,
R2 ′ and R3 ′ are
Hydrogen atoms provided that R1 ′ and R2 ′ may form a benzene ring together with adjacent carbon atoms, and R3 ′ and R4 ′ form a benzene ring together with adjacent carbon atoms. You can,
m ′ and n ′ each represent 1 or 2,
X ′ represents CO or SO ₂ ,
A '
(1) C1-C10 alkyl which may be substituted (Here, C1-C10 alkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkoxy optionally substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and aryl,
A C3-C15 cycloalkyl optionally substituted with one or more groups selected from the group consisting of hydroxy, oxo, C1-C6 alkyl and C1-C6 alkoxy;
C5-C6 cycloalkenyl,
・ Carboxy,
・ Cyano,
・ Oxo,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR15'R16 '(wherein R15' and R16 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R15 ′ and R16 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR17'R18 '(wherein R17' and R18 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of an atom, hydroxy and aryl, or aryl which may be substituted with a halogen atom or hydroxy, or R17 ′ and R18 ′ Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. Selected from the group consisting of C1-C6 alkylsulfonyl, aryl, arylcarbonyl and heteroarylcarbonyl. An amino optionally substituted with one or more groups
C1-C6 alkylsulfonyl,
An aryl optionally substituted with one or more groups selected from the group consisting of C1-C6 alkoxy optionally substituted with a halogen atom, hydroxy and aryl,
A heteroaryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo,
A C8-C10 partially unsaturated hydrocarbon condensed ring, and an aryloxy optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkanoyl,
C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of ),
(2) C2-C10 alkenyl,
(3) C3-C15 cycloalkyl which may be substituted (Here, C3-C15 cycloalkyl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
C1-C6 alkoxy,
・ Carboxy,
・ Oxo,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-C3-C15 cycloalkyl which may be substituted with one or more groups selected from the group consisting of arylcarbonyl and aryl which may be substituted with a halogen atom. ),
(4) A saturated or partially unsaturated heterocyclic ring that may be substituted (here, a saturated or partially unsaturated heterocyclic ring that may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
・ Aryl,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of formyl, halogen atoms and oxo,
Hydroxy, C1-C6 alkoxy and “C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted with aryl, —CONR19′R20 ′ (wherein R19 ′ and R20 ′ are the same or Differently, a hydrogen atom, “C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy and aryl”, or aryl which may be substituted with a halogen atom or hydroxy Or R19 ′ and R20 ′ together with the adjacent nitrogen atom may be substituted with one or more groups selected from the group consisting of “C1-C6 alkyl, C1-C6 alkanoyl and oxo” One or more groups selected from the group consisting of C1-C6 alkylsulfonyl. C1-C6 alkanoyl which may be substituted with one or more groups selected from the group consisting of “amino optionally substituted with”,
C4-C16 cycloalkylcarbonyl,
An arylcarbonyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
A heteroarylcarbonyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR21'R22 '(wherein R21' and R22 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”, or aryl optionally substituted with a halogen atom or hydroxy, or R21 ′ and R22 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
A saturated or partially unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl which may be substituted with a halogen atom, and C1-C6 alkylaminosulfonyl. ),
(5) aryl which may be substituted (here, aryl which may be substituted is a halogen atom,
・ Hydroxy,
A C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
A C1-C6 alkoxy which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
・ Carboxy,
・ Cyano,
-C2-C6 alkanoyl optionally substituted with formyl-halogen atom,
A C1-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of hydroxy, C1-C6 alkoxy and C1-C6 alkanoyloxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR23'R24 '(wherein R23' and R24 'are the same or different and each may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") -C6 alkyl ", or aryl optionally substituted with a halogen atom or hydroxy, or R23 'and R24' together with the adjacent nitrogen atom are" C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR25'R26 '(wherein R25' and R26 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl "which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl", or aryl which may be substituted with halogen atom or hydroxy, or R25 'and R26' Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. And amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl,
・ Nitro,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and C1-C6 alkyls,
Arylcarbonyl,
・ Aryloxy,
Heteroaryl,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo, and at least one selected from the group consisting of C1-C6 alkylsulfonyl Aryl optionally substituted with a group is shown. ),
(6) Heteroaryl which may be substituted (Here, heteroaryl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and saturated heterocycles,
A C1-C6 alkoxy optionally substituted with a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Nitro,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR27'R28 '(wherein R27' and R28 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R27 ′ and R28 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
C1-C6 alkyl, C1-C6 alkanoyl, C2-C7 alkoxycarbonyl optionally substituted by aryl, -CONR29'R30 '(wherein R29' and R30 'are the same or different, a hydrogen atom, "halogen C1-C6 alkyl which may be substituted with one or more groups selected from the group consisting of atom, hydroxy and aryl ", or aryl which may be substituted with a halogen atom or hydroxy, or R29 'and R30' Together with the adjacent nitrogen atom form a “nitrogen-containing saturated heterocycle optionally substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo”. C1-C6 alkylsulfonyl, one or more groups selected from the group consisting of “halogen atom, hydroxy and nitro”. An optionally substituted aryl, a saturated heterocyclic ring, and an amino optionally substituted with one or more groups selected from the group consisting of an aryloxy optionally substituted with a halogen atom,
An aryl optionally substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups,
-Aryloxy which may be substituted with one or more groups selected from the group consisting of halogen atoms and nitro groups; and-may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl Heteroaryl is shown. ),
(7) a C8-C10 partially unsaturated hydrocarbon condensed ring optionally substituted with one or more groups selected from the group consisting of a halogen atom and oxo;
(8) C1-C6 alkoxy which may be substituted (Here, C1-C6 alkoxy which may be substituted is
-Aryl, or C1-C6 alkoxy which may be substituted with C1-C6 alkoxy which may be substituted with aryl. ),
(9) Aryloxy which may be substituted (Here, aryloxy which may be substituted is
-C1-C6 alkyl which may be substituted with a halogen atom, or aryloxy which may be substituted with C2-C7 alkoxycarbonyl which may be substituted with aryl. ), Or (10) optionally substituted amino (wherein optionally substituted amino is
C1-C6 alkyl which may be substituted with a halogen atom or hydroxy, and amino which may be substituted with one or more groups selected from the group consisting of aryl which may be substituted with halogen atom or hydroxy. )
Indicates. Or a pharmaceutically acceptable salt thereof or a hydrate thereof. In the formula (I ′),
Y ′ represents N,
R1 ′ and R4 ′ are the same or different,
(1) Aryl which may be substituted (Here, the aryl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom, hydroxy or carboxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
C2-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR5'R6 '(wherein R5' and R6 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R5 ′ and R6 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
An amino optionally substituted with one or more groups selected from the group consisting of C2-C7 alkoxycarbonyl, C1-C6 alkanoyl, C1-C6 alkylsulfonyl and C1-C6 alkyl optionally substituted with aryl, and C1 A aryl which may be substituted with one or more groups selected from the group consisting of -C6 alkylsulfonyl. ),
(2) Formula (II ′)

(In the formula, CycB ′ is a 4- to 8-membered ring formed together with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and sulfur atom. Shows the structure, and CycB ′ is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR11'R12 '(wherein R11' and R12 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R11 ′ and R12 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
An amino optionally substituted with one or more groups selected from the group consisting of C2-C7 alkoxycarbonyl, C1-C6 alkanoyl, C1-C6 alkylsulfonyl and C1-C6 alkyl optionally substituted with aryl, and C1 A saturated hydrocarbon ring, an unsaturated hydrocarbon ring, a saturated heterocyclic ring or an unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of -C6 alkylsulfonyl. ) Or (3) heteroaryl,
R2 ′ and R3 ′ represent a hydrogen atom,
The nitrogen-containing saturated heterocyclic compound according to claim 2, or a pharmaceutically acceptable salt thereof, or a hydrate thereof. In the formula (I ′),
R1 ′ and R4 ′ are the same or different,
(1) Aryl which may be substituted (Here, the aryl which may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom, hydroxy or carboxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
C2-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR5'R6 '(wherein R5' and R6 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R5 ′ and R6 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
An amino optionally substituted with one or more groups selected from the group consisting of C2-C7 alkoxycarbonyl, C1-C6 alkanoyl, C1-C6 alkylsulfonyl and C1-C6 alkyl optionally substituted with aryl, and C1 A aryl which may be substituted with one or more groups selected from the group consisting of -C6 alkylsulfonyl. Or (2) Formula (II ′)

(In the formula, CycB ′ is a 4- to 8-membered ring formed together with two carbon atoms of a benzene ring adjacent to two or more atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and sulfur atom. Shows the structure, and CycB ′ is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
C1-C6 alkanoyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR11'R12 '(wherein R11' and R12 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”or aryl optionally substituted with a halogen atom or hydroxy, or R11 ′ and R12 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
An amino optionally substituted with one or more groups selected from the group consisting of C2-C7 alkoxycarbonyl, C1-C6 alkanoyl, C1-C6 alkylsulfonyl and C1-C6 alkyl optionally substituted with aryl, and C1 A saturated hydrocarbon ring, an unsaturated hydrocarbon ring, a saturated heterocyclic ring or an unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of -C6 alkylsulfonyl. A condensed ring represented by
R2 ′ and R3 ′ represent a hydrogen atom,
m ′ and n ′ represent 1,
X ′ represents CO,
A '
(1) C3-C15 cycloalkyl which may be substituted,
(Here, the optionally substituted C3-C15 cycloalkyl is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
C1-C6 alkoxy,
・ Carboxy,
・ Oxo,
C1-C6 alkanoyl,
Arylcarbonyl,
(C2-C7 alkoxycarbonyl optionally substituted with aryl, and C3-C15 cycloalkyl optionally substituted with one or more groups selected from the group consisting of aryl optionally substituted with halogen atoms) ,
(2) A saturated or partially unsaturated heterocyclic ring that may be substituted (here, a saturated or partially unsaturated heterocyclic ring that may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C6 alkyl optionally substituted with a halogen atom or hydroxy,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
・ Oxo,
・ Aryl,
-C2-C6 alkanoyl-hydroxy, C1-C6 alkoxy optionally substituted with one or more groups selected from the group consisting of formyl-halogen atom and oxo- and substituted with "C1-C6 alkyl, C1-C6 alkanoyl, aryl" C2-C7 alkoxycarbonyl, —CONR19′R20 ′ (wherein R19 ′ and R20 ′ are the same or different and each represents one or more selected from the group consisting of a hydrogen atom, “halogen atom, hydroxy and aryl”) C1-C6 alkyl which may be substituted with a group of the above, or aryl which may be substituted with a halogen atom or hydroxy, or R19 ′ and R20 ′ together with the adjacent nitrogen atom are “C1- Or substituted with one or more groups selected from the group consisting of C6 alkyl, C1-C6 alkanoyl and oxo. One or more selected from the group consisting of “amino optionally substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl”. A C1-C6 alkanoyl optionally substituted with a group,
C4-C16 cycloalkylcarbonyl,
An arylcarbonyl optionally substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
A heteroarylcarbonyl which may be substituted with one or more groups selected from the group consisting of a halogen atom, hydroxy, C1-C6 alkoxy and C1-C6 alkyl,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR21'R22 '(wherein R21' and R22 'are the same or different and may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") —C6 alkyl ”, or aryl optionally substituted with a halogen atom or hydroxy, or R21 ′ and R22 ′ together with the adjacent nitrogen atom are“ C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
A saturated or partially unsaturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkylsulfonyl which may be substituted with a halogen atom, and C1-C6 alkylaminosulfonyl. ), Or (3) aryl that may be substituted (here, aryl that may be substituted is
A halogen atom,
・ Hydroxy,
A C1-C10 alkyl which may be substituted with one or more groups selected from the group consisting of halogen atoms, hydroxy and aryl,
A C1-C6 alkoxy optionally substituted by a halogen atom or hydroxy,
・ Carboxy,
・ Cyano,
A C2-C6 alkanoyl optionally substituted with one or more groups selected from the group consisting of formyl, halogen atoms and hydroxy,
-C2-C7 alkoxycarbonyl optionally substituted by aryl,
-CONR23'R24 '(wherein R23' and R24 'are the same or different and each may be substituted with one or more groups selected from the group consisting of a hydrogen atom, "halogen atom, hydroxy and aryl") -C6 alkyl ", or aryl optionally substituted with a halogen atom or hydroxy, or R23 'and R24' together with the adjacent nitrogen atom are" C1-C6 alkyl, C1-C6 alkanoyl and oxo A nitrogen-containing saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of:
An amino optionally substituted with one or more groups selected from the group consisting of C2-C7 alkoxycarbonyl, C1-C6 alkanoyl, C1-C6 alkylsulfonyl and C1-C6 alkyl optionally substituted with aryl,
・ Nitro,
An aryl optionally substituted with a halogen atom or C1-C6 alkyl,
Arylcarbonyl,
・ Aryloxy,
Heteroaryl,
A saturated heterocyclic ring which may be substituted with one or more groups selected from the group consisting of C1-C6 alkyl, C1-C6 alkanoyl and oxo, and at least one selected from the group consisting of C1-C6 alkylsulfonyl Aryl optionally substituted with a group is shown. The nitrogen-containing saturated heterocyclic compound according to claim 3, or a pharmaceutically acceptable salt thereof, or a hydrate thereof.