WO2004048379A1 - Xanthine compound - Google Patents

Abstract

A xanthine compound represented by the following formula (I), which has high DPP-IV inhibitory activity or is improved in safety, nontoxicity, etc.; a prodrug of the compound; or a pharmaceutically acceptable salt of either.

Description

 Xanthine compounds Technical field

 The present invention relates to a novel xanthine compound useful as a medicament. More specifically, it relates to a novel xanthine compound effective as a dipeptidyl peptidase-IV (DPP-IV) inhibitor. Furthermore, the present invention relates to a therapeutic agent for diabetes mellitus 1 containing a novel xanthine compound which is effective as a dipeptidyl peptidylase-IV (DPP-IV) inhibitor as an active ingredient. Background art

 DPP-IV is a serine protease that exists widely in the body, is a type of dipeptidylaminopeptidase that hydrolyzes the N-terminal peptide, and a peptide in which the second amino acid from the N-terminal is proline. It is also known as prolyl endopeptidase because it acts particularly strongly on steroids. It is known that DPP-IV uses various biological peptides involved in endocrine system, neuroendocrine system, immune function and the like as substrates. Pancreatic polypeptides such as punk creatic polypeptide (PP) and neuropeptide Y (PY), bathoactive intestinal polypeptide petit K (VIP), glucagon-like peptides— 1 ( GLP-1), glucose-dependent insulin pick-up polypeptide (GIP), glucagon ζνιρ-family represented by growth honolemon secretagogue (GRF), etc., and many physiologically active peptides such as the chemokine family are DPP-IV. Is known to be affected by activation / inactivation and promotion of metabolism. S known (edited by J. Langner and S. Ansorge, Cellular Peptidases in Immune Functions and Disease 2 ", Advances in Experimental Medicine and Biology Vo 1. 477).

DPP-IV cleaves two amino acids (His-Ala) from the N-terminus of GLP-1. Although the cleaved peptide binds weakly to the GLP-1 receptor, it is known to have no receptor-activating action and to act as an antagoist (LB Knudsen et al., European Journal of P. harraacology, Vol. 318, p429-435, 1996). It is known that the metabolism of GLP-1 in blood by DPP-IV is very rapid, and the inhibition of DPP-IV increases the concentration of active GLP-1 in blood (TJ Kieffer et al., Endocrinology , Vol. 136, p3585- 3596, 1995). GLP-1 is a peptide secreted from the intestinal tract by sugar intake and is a major stimulator of glucose-responsive secretion of insulin in the knee. It is known that GLP-1 has an action of promoting insulin synthesis in knee cells and an action of promoting cell proliferation. Furthermore, it is known that the GLP-1 receptor is expressed in the gastrointestinal tract, liver, muscle, adipose tissue, etc., and GLP-1 is expressed in these tissues by gastrointestinal activity, gastric acid secretion, and glycogen production. It is known to act on synthesis and degradation, insulin-dependent glucose uptake, and the like. Therefore, by increasing blood GLP-1 concentration, blood glucose-dependent promotion of insulin secretion, improvement of spirulinum storage function, improvement of postprandial hyperglycemia, improvement of glucose intolerance, improvement of insulin resistance, etc. Therefore, development of a DPP-IV inhibitor effective for type 2 diabetes (non-insulin-dependent diabetes) is expected (RA Pederson et al., Diabetes Vol. 47, pl253-1258, 1998). Various DPP-IV inhibitors have been reported. For example, in WO 02/0260, a panflate (WQ 02/02560), a xanthine compound having a piperazine ring or the like inhibits DPP-IV inhibition. It is reported to be effective as an agent. In WO 02/684420 pamphlet (TO 02/68420), one of the characteristics of the compound of the present invention is a 3-aminopyridine ring or 1,2-cycloalkanediamine, etc., of xanthine. It is disclosed that the xanthin derivative at position 8 is effective as a DPP-IV inhibitor. Compounds having a benzyl group in which the 5-position on the benzene ring is a fluorine atom and the 2-position is substituted as the 7-benzyl group of the compound disclosed in the literature, such as the compound of the present invention, are as follows: Not listed at all.

In addition, WO02 / 24698 pamphlet (W002 / 24698) reports that xanthine compounds are effective as phosphodiesterase V inhibitors. Ming disclosure An object of the present invention is to provide a compound having a high DPP-IV inhibitory activity and having an antidiabetic action. The present inventors have conducted intensive studies to solve the above-mentioned problems, and as a result, have a benzyl group having a fluorine atom at the 5-position and a specific substituent at the 2-position at the 7-position of xanthine; and (1) 3_ Aminopiperidine-1-yl, 3-aminopyrrolidine-1-yl or 3-amino-hexahydroazepin-1-yl, or (2) (2-aminocycloalkyl) amino For the first time, a xanthine derivative characterized by a chemical structure having a group at the 8-position of xanthin is synthesized, and the compound or a prodrug thereof or a pharmaceutically acceptable salt thereof (hereinafter abbreviated as the compound of the present invention as necessary) Has an excellent DPP-IV inhibitory action and further has an antidiabetic action, and completed the present invention. That is, the present invention relates to the following.

[1] A xanthine compound represented by the following formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof.

[Wherein, R ¹ represents a (1) hydrogen atom, or (2) a C w alkyl group optionally substituted with one or more groups independently selected from A r 1 or A ¹ Represents

A r ¹ represents an optionally substituted aryl group, an optionally substituted aromatic heterocyclic group, or an optionally substituted, aliphatic heterocyclic group;

 X represents a single bond, an oxygen atom, one C (= 0) —, one S (O) m—, or one S (O) ra_ NH—,

 m represents 0, 1, or 2,

A ¹ is a halogen atom (1 to 3 carbon atoms may be substituted on the same carbon atom), hydroxyl group An oxo group, a cyano group, a carboxy group, a carbamoyl group optionally substituted by one or two same or different alkyl groups, an alkoxy group, an amino group,

₆ alkylamino group, dialkylamino group, hydroxyimino group, alkoxyimino group, acylamino group, C w alkoxycarbonylamino group, CH anoalkylthio group, CH alkylsulfyl group, C ^ 6 It represents ₆ cycloalkyl group or an alkyl carbonylation group, - alkylsulfonyl group, C 1-6 Anore Kokishi force Rupoeru group, § reel sulfonyl group, C ₃

R ² represents a hydrogen atom, a C _{1 H3} alkoxycarbonylmethyl group, or an alkyl group,

R ³ is a chlorine atom, a bromine atom, an iodine atom, a cyano group, a carboxy group, an optionally substituted amino group, an optionally substituted CH alkyl group, an optionally substituted C w alkylthio group, optionally substituted CH alkylsulfinyl group, optionally substituted CH alkylsulfonyl group, C ₂ - ₆ Arukeeru group, C ₂ -6 alkynyl group, an optionally substituted C w alkylcarboxy - group, Represents an optionally substituted CH alkoxy group or an optionally substituted radical group;

One Y—NH ₂ has the following formula (A)

(In the formula, n represents 0, 1, or 2, and R ⁴ is present one or two times, and independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, an oxo group, or an optionally substituted Represents a mino group, an optionally substituted alkoxy group, an optionally substituted alkyl group, an optionally substituted phenyl group, or an optionally substituted benzyl group, or R ⁴ is 2 If they are present together, they together represent methylene or ethylene, and can combine with the two carbon atoms of the ring to form a bridged ring.) Or a group represented by the following formula (B)

(In the formula, q represents 0, 1, or 2, and R ⁵ is one or two and independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, an oxo group, or a substituent. Good amino group, optionally substituted CH alkoxy group, optionally substituted ₆ alkynole group, optionally substituted alkoxycarbonyl group, optionally substituted rubamoyl group, substituted Represents a phenyl group which may be substituted or a benzyl group which may be substituted, or, when two R ⁵ are present, represents methylene or ethylene together and is bonded to two carbon atoms constituting a ring And can form a bridged ring.) ]

[2] _Y—NH ₂ is a group represented by the formula (A), and n is 1 or 2 \ or one Y—NH ₂ is a group represented by the formula (B), q [1] or a prodrug thereof, or a pharmaceutically acceptable salt thereof.

[3] —Y—NH ₂ is a group represented by the formula (A) and n is 1 or one Y—NH ₂ is a group represented by the formula (B) and q is 1 Item 1. The xanthine compound or prodrug thereof according to item [1], or a pharmaceutically acceptable salt thereof.

[4] The xanthine compound or prodrug thereof according to any one of [1] to [3], wherein R ² is a methyl group, or a pharmaceutically acceptable salt thereof.

[5] R ⁴ or R ⁵ is a hydrogen atom, a halogen atom, an optionally substituted ₆ Al kill group, or, optionally which may be substituted Ci-6 alkoxy group claim [1] to [4] The xanthine compound or prodrug thereof according to any of the above, or a pharmaceutically acceptable salt thereof.

[6] The term in which R ³ is a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, a cyano group, a trifluoromethyl group, a methoxy group, a trifluoromethoxy group, or a difluoromethoxy group [1] to The xanthine compound according to any of [5] or A prodrug thereof, or a pharmaceutically acceptable salt thereof.

[7] R ¹ is, A r ¹ - X- in a substituted alkyl group; Ar ¹ has not been also been good Ariru or substituted optionally substituted also to aromatic be heterocyclic group; A term in which X is a single bond, an oxygen atom, one C (= θ) one or one S (O) m— [1;] to

 The xanthine compound or prodrug thereof according to any of [6], or a pharmaceutically acceptable salt thereof.

[8] R ¹ is a C ^ ₂ alkyl group substituted with Ar—X—; Ar ¹ is an optionally substituted aryl group or an optionally substituted aromatic heterocyclic group; X Wherein x is a single bond or 1 C (= 0) —, the xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of the items [1] to [6].

[9] R ¹ is an ethyl group substituted at the 2-position with Ar—X—; Ar ¹ is optionally substituted phenyl, optionally substituted pyridyl, optionally substituted A xanthine compound or a prodrug thereof according to any one of [1] to [6], wherein X is a single bond, or a pharmaceutically acceptable salt thereof. Salt.

[10] R ¹ is a methyl group substituted by Ar 丄 X—; Ar ¹ is a phenyl group which may be substituted, a pyridyl group which may be substituted, and a quinolyl group which may be substituted Or the xanthine compound or prodrug thereof according to any one of [1] to [6], wherein X is one C (= o)-, or a pharmaceutically acceptable salt thereof. Acceptable salt.

[1 1] A r ¹ is section [1] is a phenyl group which may be substituted to [10] Noi deviation or the xanthine compound or a prodrug thereof or their pharmaceutically acceptable salts.

[12] The xanthine compound or prodrug thereof according to any one of [1] to [10], wherein Ar ¹ is an optionally substituted pyridyl group, or a pharmaceutically acceptable salt thereof.

[13] The xanthine compound or prodrug thereof according to any one of [1] to [6], wherein R ¹ is a hydrogen atom or a methyl group, or a pharmaceutically acceptable salt thereof. [14] The xanthine compound or prodrug thereof according to any one of [1] to [6], wherein R ¹ is a methyl group, or a pharmaceutically acceptable salt thereof.

[15] — The xanthine compound or a prodrug thereof according to any of items [1] to [14], wherein Y_NH ₂ is represented by the following formula (C), or a pharmaceutically acceptable salt thereof:

4s

[16] _Y—The xanthine compound or prodrug thereof according to any of items [1] to [14], wherein NH ₂ is represented by the following formula (D), or a pharmaceutically acceptable salt thereof:

[17] The xanthine according to item [1], which is represented by the following formula (II), (111), (IV), (V), (VI), (VII), (VIII), or (IX): A compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof.

 [18] A dipeptidyl peptidase-IV inhibitor comprising the xanthine compound according to any one of [1] to [17], a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.

 [19] A therapeutic agent for diabetes comprising the xanthine compound according to any one of [1] to [17], a prodrug thereof or a pharmaceutically acceptable salt thereof as an active ingredient.

 [20] The agent for treating diabetes according to item [19], which is used in combination with another agent for treating diabetes.

BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the terms used in the present specification will be described in detail.

 The “halogen atom” includes a fluorine atom, a chlorine atom, a bromine atom or an iodine atom.

Examples of the “alkyl group” include methyl, ethyl, propyl, isopropyl, A straight or branched chain with 1 to 6 carbon atoms, such as butinore, isobutinole, sec-butinole, tert-butinole, pentyl, 1-methinolebutyl, 2-methylbutyl, 3-methylinobutynole, 1-ethynolepropynole, hexinole, etc. Examples include a branched alkyl group. Preferred alkyl groups include linear or branched alkyl groups having 1 to 4 carbon atoms. More preferred alkyl groups include methyl or ethyl.

The "Ji ₃ alkyl group", for example methyl, Echiru, propyl, straight or branched alkyl group having 1 to 3 carbon atoms such as isopropyl.

 The “rc ^ alkyl group” includes methyl or ethyl.

The - "c _{2 6} alkenyl group", for example Bininore, propenyl, Mechirupuro Bae Interview le, linear or branched carbon atom number 2 6 having at least one double bond such as Puteyuru or Mechirubuteyuru And a branched alkenyl group. Preferred alkenyl groups include linear or branched alkenyl groups having 3 to 4 carbon atoms.

The "C ₂ _ ₆ alkynyl group", for example Echuru, Purobyuru, Mechirupuropie Honoré, Buchuru or Mechirupuchiniru, at least one straight-chain or branched alkynyl group having 2 to 6 carbon atoms having a triple bond such as Is mentioned. Preferred alkynyl groups include linear or branched alkynyl groups having 3 to 4 carbon atoms.

The - "C _{3 6} consequent opening alkyl group", cyclopropyl, cyclobutyl, Shikurobe pentyl, etc. hexyl and the like to the consequent opening.

The "Ji ^ alkoxy group", for example, Cw Arukiruokishi group, C ₃ - ₆ cycloalk Kiruokishi group. Preferred alkoxy groups include linear or branched alkoxy groups having 1 to 4 carbon atoms.

Examples of the “dialkoxy group” include a C ₃ alkyloxy group and a cyclopropyloxy group.

". ^ Alkylthio group", "C _M alkyl sulfide El group", - the alkyl in "C _L _ ₆ Arukirusunore ho le group", "Ji ^ alkylcarbonyl group", the

A C w alkyl group. Examples of the CH alkyl in the “pot ₆ alkylamino group” and the “di C w alkylamino group” include the aforementioned C _M alkyl group.

"〇_Ita alkoxy Cal Poni Le group", "C _{1 -6} alkoxycarbonyl methyl group,""

Examples of the alkoxy in the “C ₁₅ alkoxycarbonyloxy group”, the “C ₆ alkoxycarbonylamino group” and the “dialkoxyimino group” include the aforementioned CM alkoxy group.

Examples of the alkoxy in the “C ₃ alkoxycarbonyl group”, the “C ₃ -anolekoxycanolevonyloxy group”, the r C -s alkoxyl propylonylamino group, and the “C ₃ alkoxyimino group” include the C ^ alkoxy Groups.

The C ₃ _ ₆ cycloalkyl in the "C ₃ _ ₆ cycloalkyl O alkoxy group", said.

₃ - ₆ cycloalkyl group.

 Examples of the acyl in the “acylamino group” include acetyl, propioel, etc. ^

_ ₆ alkylcarbonyl group, Benzoiru, Ru is like Aroiru groups such naphthoyl.

 Examples of the “aryl group” include a phenyl group, a 1-naphthyl group, a 2-naphthyl group, an indanyl group and the like. Of these, a phenyl group is preferred.

 Examples of the “aroyl group” include arylcarbonyl groups having 11 or less carbon atoms, such as benzoyl and naphthoyl.

 Examples of the aryl in the "aryloxy group", the "arylsulfonyl group", the "arylsulfonyloxy group" and the "arylsulfonylamino group" include the above aryl groups. Examples of the arylsulfonyl group and arylsulfonyloxy group include a toluenesulfonyl group and a toluenesulfonyloxy group.

The "aromatic heterocyclic group" includes 0 to 3 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom (the sulfur atom may be oxidized by 1 or 2 oxygen atoms. ) A 5- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from the above. In the aromatic heterocyclic group in the aromatic heterocyclic group, a part of the ring system may be hydrogenated as long as it has aromaticity. Also, the aromatic heterocyclic group In the aromatic hetero ring of the above, one or more carbon atoms on the ring may be substituted with an oxo group as long as a stable structure is obtained. Here, the bonding position of the aromatic ring group is not particularly limited, and the aromatic ring group may be bonded on any nitrogen atom or carbon atom on the bondable ring.

 Specific examples of the aromatic hetero ring in the aromatic hetero ring group include furan, thiophene, pyronole, pyridine, indonele, isoindole, purine, phthalazine, 4-oxo-13,4- Dihydrophthalazine, quinoline, 1,2-dihydroquinoline, tetrahydroquinoline, isoquinoline, 2oxo_1,2-dihydroquinoline, tetrahydroisoquinoline, quinazoline, quinoxaline, naphthyridine, virazol, imidazole, triazole, pyrazole, pyrazole, pyrazole Pyrazine, pyridazine, thiazole, oxazole, isoxazole, indolizine, chroman, isochroman, 4-oxo-4H-chromene, indazonole, imidazo pyridine, imidazopyrimidine, benzimidazole 1,2-oxo-1,2,3-dihydro 1H-benzimidazono, benzothiazono, benzoisothiazo / no, benzoxoazono, 2-oxo-1,2,3-dihydro 1H-benzoxa Zonore, benzoisoxazonole, benzofuran, 2,3-dihydrobenzofuran, benzothiophene, benzo [1,3] dioxonole, 2-oxo_2,3-dihydrobenzo [1,4] dioxin, or 3-oxoone 3,4-dihydro-1 2H-benzo [1,4] oxazine and the like. In addition, a ring in which part of these rings is hydrogenated, or a ring in which one or more carbon atoms on the ring are substituted with an oxo group can also be mentioned.

 Of these, pyridine, quinoline, and isoquinoline are preferable, and pyridine is more preferable.

 Examples of the pyridyl group include a 2-pyridyl group, a 3-pyridyl group, and a 4-pyridyl group.

Examples of the aliphatic heterocyclic group include 0 to 3 nitrogen atoms, 0 to 1 oxygen atom, and 0 to 1 sulfur atom (the sulfur atom may be oxidized by 1 or 2 oxygen atoms). Examples thereof include a 5- to 10-membered monocyclic or bicyclic heterocyclic group containing 1 to 3 heteroatoms selected from the group consisting of the following. The aliphatic heterocyclic group may have a partially unsaturated bond. Good. Further, in the aliphatic heterocyclic group, one or more carbon atoms on the ring may be substituted with an oxo group as long as a stable structure is obtained. Here, the bonding position of the aliphatic heterocyclic group is not particularly limited, and it may be bonded on any nitrogen or carbon atom on the bondable ring.

 Specific examples of the aliphatic hetero ring in the aliphatic hetero ring group include pyrrolidine, 2-oxopyrrolidine, pyrroline, piperidine, piperazine (the nitrogen atom of the piperazine is substituted with methyl or ethyl. ), 2-oxoimidazolidine, 2,4-dioxoimidazolidine, monoreforin, thiomonoreforin, thiomorpholine-l-oxide, or aliphatic heterocycle such as thiomorpholine-l, l-dioxide. And the like.

Optionally substituted alkyl groups, optionally substituted C ₂ - ₆ alkenyl group

, Optionally substituted C ₃ - ₆ cycloalkyl group, an optionally substituted alkoxy group, an optionally substituted C ^ alkyl Cal Poni group, an optionally substituted C w alkylthio group, substituted Examples of the substituent in the optionally substituted alkylsulfier group, the optionally substituted alkylsulfonyl group, the optionally substituted phenyl group and the optionally substituted benzyl group include the halogeno described above. emissions atoms (which may have 1 to 3 substituent on the same carbon atom), a hydroxyl group, Shiano group, forces Rubokishi group, c ₂ _ ₆ alkenyl, c ₂ _ ₆ alkynyl group, c ₃ _ ₆ cycloalkyl group , 〇

₆ alkoxy group, alkylcarbonyl El group, C ₆ alkoxy force Lupo - group, optionally substituted force Rubamoiru group, an amino group, C _i-6 alkylamino group, di C w alkyl Ruamino group, the aliphatic heterocyclic group, Ashiruamino group, 〇 ₆ alkyl sulfonyl Ruamino group; § reel sulfonyl § amino group, Ji Bok ₆ alkoxy force Ruponiruamino group, C _i-6 Al Kiruchio group, an alkyl sulfide El group, an alkylsulfonyl - group, Ariru Examples thereof include a sulfo group, and one or more of these substituents may be present. Further, examples of the substituent in the optionally substituted phenyl group and the optionally substituted benzyl group include the above-mentioned optionally substituted alkyl group.

The substituent in the optionally substituted amino group, for example, the above optionally substituted alkyl groups, optionally substituted C ₃ - ₆ cycloalkyl group, C ^ Examples thereof include an alkylcarbonyl group, an aryloyl group, a C w alkoxycarboyl group, a _6- alkylsulfol group, and an arylsulfonyl group. One or two of these substituents may be present.

 Specific examples of the substituted amino group include, for example, a methylamino group, an ethylamino group, a dimethylamino group, an acetylamino group, a propionylamino group, a benzoylamino group, a naphthoinoleamino group, a methoxycarbonylamino group, an ethoxycarbonylamino group and a tert-carbonyl group. -Ptoxycanolepoenolenamino group, methinolesnolephoenolamino group, etinolesnolehonylamino group and the like.

The substituent in the optionally substituted force Rubamoiru group, for example an optionally substituted alkyl group, C ₃ _ ₆ cycloalkyl group, C ₃ - ₆ cycloalkyl substituted by a C Bok ₃ alkyl group, the alkyl Examples thereof include a carbonyl group and an arylo group, and one or two of these substituents may be present.

 Further, two substituents of the carbamoyl group are bonded to form pyrrolidine, piperidine, monoreforin, thiomorpholine, thiomonorephorin oxide, thiomonorephorin dioxide, or piperazine (of the piperazine). The nitrogen atom may be substituted with methyl or ethyl), and the like, to form an aliphatic heterocyclic ring which may contain carbon, nitrogen, oxygen or sulfur.

 Specific examples of the substituent rubamoyl group include, for example, monomethylcarbamoyl, dimethylenorecanolebamoinole, echinorecanolebamoinole, jetinorecanolebamoinole, N-propinolecanole vamoyl, N-isopropyl rubamoinole, N— Ethyl-N-methylcarbamoyl,

N-Methinole-N-propynolecanolebamoinole, N-cyclopropinolecanolebamoinole, N-cyclopropinolemethanolebanoinole, acetinole force / rebamoinole, benzoinolecanolebamoyl, pylori Dinocarbonyl, piperidinocarbonyl, morpholinocarbonyl and the like.

Examples of the substituent in the aryl group which may be substituted or the aromatic heterocyclic group which may be substituted include a halogen atom, a hydroxyl group, a carboxy group, a cyano group, an amino group, a nitro group and a substituted group. (the substituent here, a halogen atom, an alkyl group, an alkoxycarbonyl group, C 3 alkoxy force Ruponiruokishi group or the like carboxyl group) is also an alkyl group, C ₂ - ₆ Aruke - group, C ₂ _ ₆ alkynyl, C ₃ _ ₆ cycloalkyl group, an optionally substituted Cw alkoxy group, C ₃ _ ₆ cycloalkyl O alkoxy group, an alkylcarbonyl group, C w alkylthio group, an alkyl sulfide El group, Cw alkylsulfonyl El group, 1-2 same or properly are different alkyl groups optionally substituted amino group, CH alkylcarbonyl two Ruamino group, C ₆ alkoxycarbonyl § amino group, CH alkylsulfonyl § amino group, a force Rubamoiru Group, sulfamoyl group, ureido group, thioureido group, aminocalponyloxy group, aminosnolephoninoleamino group (here, carbamoyl group, sulfamoyl group, ureido group, thioureido group, aminocarboxyloxy group, aminosulfonylamino group , Substituted by one or two identical or different alkyl groups May be), C _{1 -6} § Roh record alkoxycarbonylmethyl § amino group, an alkyl Cal Bamo Ino les methylcarbamoyl Honoré amino group, C i - ₆ § Bruno record alkoxycarbonyl § iminocarbonyl § amino group, carboxymethyl butoxy group, A cyanomethoxy group, a CH alkoxycarbonylmethyloxy group, a cyanomethylamino group, an N-methyl-N-cyanomethylamino group, an aryl group, an aryloxy group, and an arylsulfonyloxy group, 2-oxoimidazolinyl group, 3-methyl-2-oxoimidazolinyl group, 3-methyl-1,2,4-dioxoimidazolidinyl group, 2-oxotetrahydropyrimidinyl group, or 3-methyl-2-oxo Examples thereof include a tetrahydropyrimidyl group, and one or more of these substituents may be substituted. The substitution position of the substituent is not particularly limited, and the substituent may be substituted on any nitrogen atom or carbon atom on the bondable ring.

Examples of substituents in substituted optionally heterocyclic group to an aliphatic, hydroxyl, Karupokishi group, ₃ alkyl group, d_ ₃ alkoxy groups, C Bok ₃ alkylcarbonyl § Mi amino group, an alkylsulfonyl § amino group, It may be mentioned 1 or 2 identical or different 〇 preparative ₃ alkyl group an amino group which may be substituted, and 1 or 2 identical or different ₃ alkyl optionally force Rubamoinore group optionally substituted with a group, these May have one or more substituents. The substitution position of the substituent is not particularly limited, and the substituent may be substituted on any nitrogen atom or carbon atom on the bondable ring.

In Ar ¹ , an optionally substituted phenyl group, an optionally substituted pyridyl group, an optionally substituted quinolyl group, and an optionally substituted isoquinolyl group The substituent in the aryl group may be the same as the substituent in the aromatic heterocyclic group which may be substituted or may be substituted, and these substituents may be 1 or A plurality may be substituted. Substitution positions on A r ¹ substituent, and the bonding position of A r ¹ that bind to X is not particularly limited, substituted or bound on any nitrogen atom or carbon atom bondable on the ring May be.

In Ar ¹ , the optionally substituted phenyl group preferably has an ortho position or a meta position.

In Ar ¹ , the substituent of the optionally substituted phenyl group is preferably a fluorine atom, a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, a cyano group, a trifluoromethyl group, a methoxy group. Group, trifluoromethyoxy group, difluoromethoxy group, amino group, methylthio group, methylsulfinyl group, or methylsulfoninole group.

As “prodrugs”, those which can be easily hydrolyzed in vivo to regenerate the xanthine compound of the present invention, specifically, for example, the amino group of the xanthine compound: 1 NH ₂ (1) Compounds derived from NHQ. Here, Q has the following significance.

(2) One COR ¹⁷

(3) — COO_CR ¹⁸ (R ¹⁹ ) _OCOR ²⁰

(4) -COOR ²¹

[In the formula, R ¹⁷ represents a hydrogen atom, an alkyl group, or an optionally substituted phenyl group or an aryl group such as a naphthyl group. R ¹⁸ and R ¹⁹ independently represent a hydrogen atom or an alkyl group. R ² ° represents a hydrogen atom, ₆ alkyl, the above-mentioned aryl group or benzyl group. R ²¹ represents an alkyl group or a benzyl group. ] Preferred Q includes the group (1) and the group (3). Preferred examples of the group (3) include those in which R ¹⁸ is a hydrogen atom, R ¹⁹ is a hydrogen atom, methyl or ethyl, and R ²⁰ is a hydrogen atom, methyl or ethyl. These compounds can be produced according to a conventional method (J. Med. Chem. 35, 4727 (1992), WO 01/40180, etc.). In addition, prodrugs can be produced under physiological conditions as described in Hirokawa Shoten, 1990, “Development of Drugs, Vol. 7, Molecular Design,” pp. 163 to 198. May be changed.

“Pharmaceutically acceptable salts” include, for example, inorganic salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, or acetate, propionate, succinate, lactate, Organic acid salts such as malate, tartrate, citrate, maleate, fumarate, methanesulfonate, p-toluenesulfonate, and ascorbate are exemplified. The present invention also includes solvates such as hydrates and ethanol solvates of a xanthine compound, a prodrug thereof, or a pharmaceutically acceptable salt thereof. Furthermore, the present invention includes all tautomers of the xanthine compound, all existing stereoisomers, and all forms of crystalline forms. Preferred examples of the xanthine compound of the present invention include the following 3-aminobiperidine compounds.

 (1) 1- (methoxycarbonylmethinole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (2) 1- (Ethoxycarbonylmethyl) -3_methyl-7- (2-co-mouth-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (3) 1-methyl 3- (methoxycarbonylmethyl) -7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidine-1-yl) -xanthine

(4) 1-Methyl-3- (ethoxycarbonylmethyl) -7- (2-chloro-5-fluorobenzyl) -8- (3-Aminopiperidine-1-yl) -xanthine (5) 1- (benzyl) -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidin-1-yl) -xanthine

 (6) 1- (3-Phenylpropyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

 (7) 1- (2-Hydroxyethyl) -3-methyl-7_ (2-methynole-5_fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (8) 1- (2-Methoxyxetyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (9) 1- [2- (Dimethylamino) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (10) 1- [2- (2,4,6-trimethylphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (1 1) 1- [2- (2,4-dichlorophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) _8_ (3-aminopyridin-1-yl) -Xanthine

 (1 2) 1- (2-thiophen-2-yl) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl)-8- (3-aminopyridin-1-yl)- Xanthine

 (1 3) 1- (2-thiophen-3-inole) -3-methyl-7- (2-methyl-5-fluoromouth benzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (14) 1_ [2- (4_tert_butylphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (1 5) 1- [2- (2-Fluoropheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine_1-inole) -Xanthine

 (1 6) 1- [2- (2-methylpheninole) ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzene) -8- (3-aminopyridin-1-yl) Le) -xanthine

 (1 7) 1- [2_ (3_methylphenyl) ethyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (1 8) 1- [2- (1-naphthyl) ethyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl) _8- (3-aminopyridin-1-yl) -xanthine

(1 9) 1- [2- (2-Naphthyl) ethynole] -3-methyl-7- (2-methyl-5-benzyl at phnoleo) -8 -(3-Aminobiperidine-1-inole) -xanthine

 (20) 1- (4-Phenylbutyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) _8- (3-aminopiperidine-1-inole) -xanthine

 (21) 1_ [2_ (3-Trifluoromethylpheninole) ethyl] -3-methyl-7- (2-methyl-5-benzyl phenol) -8- (3-aminopyridin-1-yl Le) -xanthine

 (22) 1- [2- (Pyridin-2-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -Xanthine

 (23) 1- [2- (Pyro-inole-1-yl) ethyl] -3-methinole-7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl ) -Xanthine

 (24) 1- [2-([1,2,3] triazol_1-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

 (25) 1- [2- (Pyridin-4-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1_yl) -Xanthine

 (26) 1- (3-butene-1-yl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminobiperidine-1-inole) -xanthine

 (27) 1- (4-Pentin-1-inole) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8- (3-Aminopiperidine-1-yl) -xanthine

 (28) 1- [2- (4-Methynolethiazolone-5-yl) ethynole] -3-methynole-7- (2-methyl-5-funolebenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

 (29) 1- [2- (3-Promophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobendinole)-8- (3-aminopiperidine-1-yl / xanthine)

 (30) 1- [2- (3-c-mouth pheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) Le) -xanthine

 (31) 1-((E) -2-Fenylvinyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl)- Xanthine

 (32) 1- [2- (2-chloropheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzene) -8- (3-aminopyridinidine-1-) Yl) -xanthine

(33) 1- [2- (2-Trifluoromethylpheninole) ethyl] -3-methinole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine (34) 1_ [2- (2-Promophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-inole) -xanthine

 (35) 1- [2- (3-Fluoromethyl) ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzene)-8_ (3-aminopiperidine-1-y Le) -xanthine

 (36) 1- [2- (3-N-Fetinole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopyrrolidin-1-y Le) -xanthine

 (37) 1- [2- (4-Methylphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) _8_ (3-aminopyridin-1-yl) -xanthine

 (38) 1- [2- (4-Hydroxyphenyl) ethyl] _3-methyl_7- (2-methyl-5-fluorobenzinole) -8- (3-aminopyridin-1-yl) -xanthine

 (39) 1 [2- (3-Hydroxypheninole) ethynole] _3-methyl-7- (2-methynole-5-phenylole-benzyl) -8- (3-aminopyridin-1-yl)- Xanthine

 (40) 1-[(Methoxycarbonyl) methyl] _3-methyl-7- (2-methyl_5_fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (41) 1- [2- (Methoxycarbinole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -Xanthine

 (42) 1-phenyl-3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (43) 1- [2- (3,5-Difluoropheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl Le) -xanthine

 (44) 1- [2- (2,6-Difluoropheninole) ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl) -xanthine

 (45) 1- [2- (thiophen-3-yl) -2-oxoxethyl] -3-methyl-7- (2-methyl-5-phenolylbenzinole)-8- (3-aminopyridino) Lysine-1-yl) -xanthine

 (46) 1- [2- (3-Cyanometooxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) _8- (3-aminopyridin-1-y Le) -xanthine

 (47) 1- [2- (3-benzyloxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1- Inole) -xanthine

(48) 1- [2- (3-Phenylsulfonyloxyphenyl) -2-oxoethyl] -3-methynole- 7- (2-Methyl-5-fluoromethyl) -8- (3-aminopyridin-1_yl) -xanthine

(49) 1- [2- (3-Hydroxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1- Le) -xanthine

 (5 0) 1- [2- (3,5-Dimethoxyphenyl) ethyl] -3-Methinole-7- (2-Methyl-5-fluoro mouth benzyl) -8- (3-Aminopiperidine-1-y Le) -xanthine

 (5 1) 1- [3- (Methoxycarbonyl) propyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (5 2) 1- {2- [4- (ethoxycarbonyl) phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-y Le) -xanthine

 (5 3) 1- (Phenylsulfonylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-yl) -xanthine

 (54) 1- (Fuelsulfinylmethinole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (5 5) 1_ (2-Methoxycarbonyl-2-pentopen-1-yl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

 (5 6) 1-[(Pyridin-2-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidin-1-yl)- Xanthine

 (5 7) 1-C2- (3-Pheninoleoxy-pheninole) -2-oxo-ethynole] -3-Methyl-7- (2-methyl-5_fluorobenzyl) -8- (3-aminopiぺ Lysine-1-inole) -xanthine '

 (5 8) 1- [2- (3-amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-yl) -xanthine

 (5 9) 1- (2- {3- [bis (methanesulfonyl) -amino] -phenyl} -2-oxo-ethynole) -3-methyl-7- (2-methyl-5-fluorobenzyl ) -8- (3-Aminopiperidine-1-inole) -xanthin

 (6 0) 1- [2- (2-bromo-5-dimethylamino-pheninole) -2-oxo-ethyl] -3-methinole -7- (2-methyl-5-fluorobenzenole) -8 -(3-aminopiperidine-1-yl) -xanthine

(61) 1- [2- (3-Nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

(62) 1- [2- (3-Methoxycarbonylamino-phenyl) -2-oxo-ethyl] -3-methyl -7- (2-Methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

(63) 1- [2- (3-acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-amino Piperidine-1-inole) -xanthine

 (64) 1- [2- (3-{[(ethoxycarbonylcarbonyl) amino] amino-2-amino) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5 -Fluoro mouth benzyl) -8- (3-Aminopiperidin-1-yl) -xanthine,

 (65) 1- [2- (3-cyanomethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- ( 3-aminopiperidine-1-yl) -xanthine

 (66) 1-[(thiazol-2-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopyridin-1-yl) -xanthine

 (67) 1-[(isoquinolin-1-yl) methyl] -3-methynole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (68) 1-[(isoquinoline-4-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (69) 1-[(Benzo [d] isothiazole-3-yl) methyl] -3-methyl_7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -Xanthine

 (70) 1_ [(Benzo [d] isoxazolyl-3-inole) methyl]-3-methyl _7_ (2_methyl _5_fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (71) 1-[(pyridine-3-yl) methyl] -3-methinole-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopyridin-1-yl) ) -Xanthin

 (72) 1-[(pyridine-4-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopyridin-1-yl) -xanthine

 (73) 1-[(Isoxazole-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopyridin-1-ynole) -xanthine

 (74) 1-[(1-Naphthyl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (75) 1-[(Aminocarbonyl) methyl] -3-methyl_7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

(76) 1- [2- (3-Methanesulfonylamino-phenyl) -2-oxo-ethyl] -3-methylinole- 7- (2-Methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl) -xanthine (77) 1_ [2- (2-ditro-phenyl) -2-oxo- -Ethyl] -3-Methyl-7- (2-methyl-5-fluorobenzinole)-8- (3-Aminopiperidine-1-yl) -xanthine

 (78) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-phenololobenzinole) -8- (3-a Minopiperidine-1-inole) -xanthine

 (79) 1- [2- {3-[(Methylamino) thiocarbonylamino] -phenyl} -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl )-8- (3-Aminopiperidine-toyl

) -Xanthine

 (80) 1_ [2- (2-Acetylamino-phenyl) -2-oxo-ethyl]-3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-amino Piperidine-1-yl) -xanthine

 (81) 1-[(6-Methyl-pyridin-2-yl) methyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8- (3-aminopyridinidine-1- (Inole) -xanthine

 (82) 1-[(1-Methyl-1 I-toindazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- Tyl)-Xanthine

 (83) 1- (2- {3-[(Methoxycarbonyl) methylamino] -phenyl} -2_oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl ) -8- (3-Aminopiperidine-1-inole) -xanthine

 (84) 1-cyanomethyl-3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

 (85) 1_ [2- (2-hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Inore) -Xanthine

 (86) 1- [2- (2-Methanesulfonyl-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluoromouth benzyl) -8- (3-α Minopiperidine-1-yl) -xanthine

 (87) [2- {2-[(Methoxycarbonyl) methoxy] -phenyl} -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 -(3-aminopyridin-1-yl) -xanthin

 (88) 1- [2- (2-Cyanometooxy-phenyl) -2_oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-amino Piperidine-1-yl) -xanthine

(89) 1- (2-{3-[(Methylaminocarboyl) methoxy] -phenyl 2-oxo-ethy Nore) -3--Methinole-7- (2-Methyl-5-fluorobenzinole)-8- (3-Aminopiperidine-1-inole) -Xanthine

 (90) 1_ (2- {3-[(aminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (91) 1_ (2- {3_ [(dimethylaminopropyl) amino] -phenyl} -2-oxo-ethynole) -3-methyl-7- (2-methyl-5-fluorobenzyl ) -8- (3-Aminopiperidine-1 1-inole)-Xanthine

 (92) 1- (4-oxo-4H-chromen-3-yl) -3-methyl-7- (2-methinole-5_fluorobenzyl) -8- (3-aminopyridin-1-yl ) -Xanthine

 (93) [[3-Methyl-pyridin-2-yl) methyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) ) -Xanthine

 (94) 1-[(5-Methyl-pyridin-2-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine-1- Yl) -xanthine

 (95) 1-[(4-Methyl-pyridin-2-ynole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridinidine-1-y Le) -xanthine

 (96) 1-[(quinolin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl) -xanthine

 (97) 1-[(quinolin-8-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminobiperidin-1-yl) -xanthine

 (98) 1-[(5-Nitro-isoquinolin-1-yl) methyl] _3-methyl-7- (2-methyl-5-fluorobenzinole) -8_ (3-aminopiperidine-1 -Inore) -Xanthine

 (99) 1-[(2-oxo-1,2-dihydro-quinoline-4-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopi Lysine-1-yl) -xanthine

 (100) 1-[(5-Amino-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-Aminopiperidine_1- Inole) -xanthine

 (101) 1- [2- (3-Aminosulfonyl-phenyl) -2-oxo-ethyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl) _8- (3-aminopiperidine-1 -Yill) -Xanthine

(102) 1- (2-Phenoxy-ethyl) -3-methinole-7- (2-methinole _5 -fluorobenzil ) -8- (3-Aminobiperidine-1_yl) -xanthine

 (103) 1-carboxymethyl-3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminobiperidine-1-yl) -xanthine

 (104) 1- (3-propoxy-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (105) 1- [2- (4-Carboxy-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fuesulobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (106) 1- (2-phenyl-ethynole) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidine-1-yl) -xanthine

 (107) 1- [2- (3-Amino-phenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-Aminopiperidine-1-inole ) -Xanthin

 (108) 1- [2- (Pyrrolidin-1-yl) ethyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -Xanthine

 (109) 1— [2- (piperidine-1-inole) ethyl ']-3-methyl-7- (2-methinole-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (1 10) 1- [2- (morpholin-4-ynole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8_ (3-aminopiperidin-1-yl ) -Xanthine

 (1 1 1) 1- [2- (Piperazin-1-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1 -Yill) -Xanthine

 (1 12) 1- [2- (4-Methyl-piperazine-1-inole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-inole) -xanthine

 (1 13) 1- (3-Hydroxypropynole) -3-methyl_7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (1 14) 1_ (3-Methoxypropyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

 (1 15) 1- (3-ethoxypropyl) -3-methyl-7- (2-methinole-5-fluorobenzyl) -8- (3-aminobiperidine-1-yl) -xanthine

(1 16) 1- [3- (Dimethylamino) propyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8- (3-aminopyridin-1-yl) -xanthine (1 17) 1- [3_ (pyrrolidine-1-yl) propyl] -3_methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl) -Xanthine

 (1 18) 1_ [3- (morpholin-4-yl) propyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -Xanthine

 (1 19) 1- [3- (Piperazin-1-inole) pu pill] -3-Methyl-7- (2-methyl-5-fluoro benzyl) -8- (3-Aminopiperidine-1- Yl)-xanthine

 (120) 1- [3- (4-Methyl-piperazine-1-yl) propyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-Inole) -Xanthine

 (121) tri (pyrrolidine-1-yl-carbonylmethyl) -3-methyl-7- (2-methyl-5-phenol) -8- (3-aminopiperidine-1-yl)- Xanthine

 (122) 1- (Pyridin-1-yl-carbonylcarbonyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidine-1 -Isle) -Xanthine

 (1 23) 1- (morpholin-4-yl-carbonylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8_ (3-aminopiperidine-1-inole) -Xanthine

 (124) 1- [2- (3-Fluoro mouth-4-hydroxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

 (125) 1- [2- (4-Methoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluoromethyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (126) 1- [2- (4-Ethoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidine-1 -y Le) -xanthine

 (127) 1- (2- {4-[(carboxymethyl) oxy] -phenyl} -ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-amino Piperidine-1-yl) -xanthine

 (128) 1- [2- (2-Fluoro-5-hydroxy-phenyl) -ethyl] _3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl)-xanthine

 (129) 1- [2- (3-Methoxy-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluoro-benzyl) -8- (3-aminopyridin-1 -Inole) -Xanthine

 (130) 1- {2_ [3- (carboxymethyloxy) -phenyl] -ethyl 3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl)-xanthine

(131) 1- (2- {3_ [(ethoxycarbonyl) methyloxy] -fuel} -ethyl) -3- Methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopyridin-1-y / le) -xanthine

 (132) 1- [2- (2-Hydroxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (133) 1- [2- (2-Methoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluoromouth benzyl) -8- (3-aminopyridin-1-y Le) -xanthine

 (134) 1- {2- [2- (carboxymethyloxy) -phenyl] -ethyl} -3-methyl-7_ (2-methyl-5-fluorobenzinole) -8- (3- Aminopiperidine-1-inole) -xanthine

 (135) 1- (2- {2 _ [(methoxycarbonyl) methyloxy] -phenyl} -ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiぺ lysin-1-inole) -xanthine

 (136) 1- [2- (4-Hydroxymethyl-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (137) 1- {2- [4- (Methoxycarbonyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-amino Piperidine-1-yl) -xanthine

 (138) 1- {2- [4- (carboxymethyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl_5-fluorobenzyl) -8- (3-aminopyridin-1-yl ) -Xanthine

 (1 39) 1- (2- {4-[(Methoxycarbonyl) methyl] -phenyltoethyl) _3-methinole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridinyl- 1-yl) -xanthine (140) 1- {2- [4- (2-potoxy-ethyl) -furyl] -ethyl} -3-methyl-7- (2-methyl-5-fluoroben Ginole) -8- (3-Aminopiperidine-1-inole) -xanthine

 (141) 1- (2- {4-[2- (methoxycanoleponinole) -ethinole] -feninole} -ethinole) -3-methinole-7- (2-methyl-5-fluorobenzyl) -8 -(3-aminopyridin-1-yl) -xanthine

(142) 1- [2- (3-Methyl-phenyl) -ethyl]-3-methyl-7- (2-methyl-5-fluorobenzinole)-8_ (3-aminopiperidine-1-yl)- Xanthine

 (143) 1- [2- (3-carboxy-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-phenylphenol) -8- (3-aminopyridin-1-y Le) -xanthine

(144) 1_ {2- [3- (ethoxycarbonyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-inole) -xanthine (145) 1- {2- [3- (carboxymethyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-phenylphenol)-8- (3-aminopyrididine -1-yl)-xanthine

 (146) 1_ (2- {3-[(Methoxycarbo-nore) methyl] -phenyltoethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-inole) -xanthine (147) 1- {2- [3- (2-carboxy-ethyl) -phenyl] -ethyl} _3-methyl-7- (2-methyl-5-fluorobenzino Re) -8- (3-Aminopiperidine-1-y / re) -Xanthine

 (148) 1-(2- {3_ [2- (Methoxycarbonyl) -ethyl] -phenyl} _ethyl) -3-methyl-7- (2-methyl-5-benzyl at the phenol) -8 -(3-aminopyridin-1-yl) -xanthine

(149) 1- [2- (2-Methynole-phenyl) -ethynole] -3-Methyl-7_ (2-methyl-5-fluorobenzinole) _8- (3-Aminopiperidin-1-yl) -xanthine

 (1 50) 1- [2- (2-potoxy-phenyl) -ethyl] -3-methinole-7- (2-methinole-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (1 5 1) 1- {2_ [2- (Methoxycarbonyl) -phenyl] -ethyl} -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (1 52) 1- [2- (4-Fluoro-mouth) -ethyl]-3-methyl-7- (2-methyl-5-fluoro-benzyl)-8- (3-aminopiperidine -1-yl) -xanthine

 (1 5 3) 1- [2- (4-chloro-phenyl) -ethyl] _3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (1 54) 1- [2- (4-Pu-mo-pheninole) -ethyl] -3--Methinole-7- (2-Methyl-5-fluoro-benzyl)-8- (3-Aminopiperidine -1-yl) -xanthine

 (1 5 5) 1- [2- (4-cyano-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) _8- (3-aminopiperidine-1-yl ) -Xanthine

 (1 56) 1- [2- (4-Trifluoromethoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine-1-y Le) -xanthine

 (1 5 7) 1_ [2- (4-methylsulfanyl-phenyl) -ethyl] -3-methinole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl)-xanthine

 (1 58) 1- [2- (4-Methylsulfinyl-pheninole) -ethyl] -3-methyl-7- (2-methinole-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

(1 5 9) 1- [2- (4-Methylsulfonyl-pheninole) -ethyl] -3-methyl-7_ (2-methinole-5 -Fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

(160) 1- [2- (4-Trifluoromethyl-phenyl) -ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (166) 1- [2- (4-Amino-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (1 6 2) 1- (2- {4-[(methylmethyl) amino] -phenylethyl) -3-methinole-7- (2-methinole-5-fluorobenzyl) -8- (3-a Minopiperidine-1-inole) -xanthine

(1 6 3) 1- (2- {4_ [(methylsulfonyl) amino] -phenyl} -ethyl) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8- (3- Aminopyridin-1-yl) -xanthine (1 64) 1- {2_ [4- (aminopropyl) -phenyl; cenyl] -ethyl} _3-methyl-7- (2-methyl- 5-Fluorobenzyl) _8- (3-aminopyridin-1-yl) -xanthine

 (1 6 5) 1- {2- [4- (methylaminopropyl) -phenyl] -ethyl} -3-methylino-7- (2-methyl-5-phenylphenol) -8- ( 3-aminopyridin-1-yl) -xanthine

(166) 1- {2- [4- (dimethylaminocarbonyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-α Minopiperidine-1-inole) -xanthine

(1 6 7) 1- {2- [4- (aminosulfonyl) -phenyl] -ethyl} -3-methyl-7 (2-methyl-5-fluorobenzinole) -8- (3- Aminopiperidine-1-inole) -xanthine

 (1 6 8) 1- {2- [4- (methylaminosulfonyl) -phenyl] -ethyl} -3-methinole-7- (2-methinole-5-funolenobenzinole) Minopiperidine-tolyl) xanthine (1 6 9) 1- {2- [4- (dimethylaminosulfonyl) -phenyl] -ethyl} -3-methyl-7- (2_methyl-5 -Fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

(170) 1- [3- (Ethoxycarbonyl) -propyl] -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-inole) -Xanthine

 (17 1) 1- [2- (3,4-dimethyl-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-Inole) -Xanthine

 (1 7 2) 1- [2- (2-Fluoro-5-chloro-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8 -(3-Aminopiperidine-1-inole) -xanthine

(1773) 1- [2- (3,5-Dimethoxy-phenyl) -ethyl] -3-methyl_7_ (2-methyl-5-phenolo-benzyl) -8- (3-amino Piperidine-1-yl) -xanthine (1 74) 1_ [2- (naphthalen-2-yl) -ethyl] -3-methylinole-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine-1-yl ) -Xanthine

 (175) 1_ [2_ (pyridine-3-inole) -ethyl]-3-methyl-7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl)- Xanthine

 (176) 1- [4-Phenyl-butyl] -3-methyl-7- (2-methinole-5-fluorobenzyl) _8- (3-aminopiperidine-1-inole) -xanthine

 (177) 1- (2-Phenylsulfonyl-ethynole) -3-methyl-7- (2-methyl-5-fluorobenzyl) _8_ (3-aminopyridin-1-yl) -xanthine

 (178) 1- (2-Phenylsulfinyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) —8- (3-Aminopiperidin-1-yl) -xanthine

 (179) 1- (2-Phenylsulfoel-ethynole) -3-methyl-7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (180) 1- [2- (3-Fluoro-mouth) -2-oxo-ethynole] -3-Methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine -Yl)-xanthine

 (181) 1_ [2- (3-chloro-phenyl) -2-oxo-ethyl] -3- 3-methyl-7- (2-methyl_5-fluorobenzyl) -8- (3-aminopyridin-1-y Le) -xanthine

 (182) 1_ [2- (3-Promo-phenyl) -2-oxo-ethynole] _3-Methinole-7- (2-Methynole-5-fluorobenzyl) -8- (3-Aminopiperidine-1- Yl)-xanthine

 (1 83) 1- [2- (3-Methyl-phenyl) -2-oxo-ethyl]-3-methyl_7_ (2-methyl_5-fluorobenzyl) -8- (3-aminopyridin-1-yl) ) -Xanthine

 (184) 1- [2- (3-Trifluoromethyl-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methinole_5-fluorobenzyl)-8- (3-aminopiperidine -1-yl)-xanthine

(185) 1- [2- (2-Methyl-phenyl) -2_oxo-ethyl] -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1- Inole) -xanthine

 (186) 1- [2- (3-Difluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

(187) 1- [2- (3-Trifluoromethoxy-phenyl) -2_oxo-ethyl] -3- 3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl) -xanthine

(188) 1- [2- (3-ethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl- 5-Fluorobenzoyl) -8- (3-aminopyridin-1-yl) -xanthine

(189) 1- [2- (3-Isopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3- (Aminopiperidine-1-yl) -xanthine

(190) 1- [2- (3-Cyclopropyloxy-phenyl) -2-oxo-ethyl] -3-methinole-7- (2-methyl-5-phenylene-ole-benzyl) -8- (3 -Aminopiperidine-1-yl) -Xanthine

(1 91) 1- [2- (3-cyclopentyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-α Minopiperidine-1-yl) -xanthine

(192) 1- [2- (3-Cyclopropylmethoxy-phenyl) -2-oxo-ethyl] -3-methylen-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyrぺ lysine-1-yl) -xanthine (193) 1- {2- [3- (2,2,2-trifluoroethoxy) -phenyl] -2-oxo-ethyl} _3-methyl-7 -(2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthin

 (1 94) 1- [2_ (4-Hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-yl) -xanthine

 (1 95) 1- {2_ [3_ (methylcarbonylamino) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3 -Aminopiperidine-1-yl) -xanthine

 (196) 1- {2- [3- (Aminocarbonylamino) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (197) 1- {2- [3- (Methylamino propylonylamino) -phenyl] -2_oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) _8- (3-aminopiperidine -1-yl)-Ki Sanchin

 (198) 1- {2- [3- (Dimethylaminocarbonylamino) -phenyl] -2-oxo-ethyl}-3-methyl-7- (2-methinole-5-fluorobenzyl)- 8_ (3-aminopyridin-1-inole)-xanthine

(1 99) 1- {2- [3- (Methylsulfonylamino) -phenyl] -2-oxo-ethyl} -1-methylinole-7- (2-Methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine (200) 1- {2- [3- (Aminosulfonyl) -pheninole] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiぺ lysin-1-yl) -xanthine

(201) 1- {2- [3- (methylaminosulfonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- ( 3-aminopyridin-1-yl) -xanthine

 (202) 1- {2- [3- (Dimethylaminosulfonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3- Aminopiperidine-1-yl) -xanthine

 (203) 1_ [2- (3-Ethyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5_fluorobenzyl) -8- (3-aminopiperidine-1 -Inole) -Xanthine

 (204) 1- [2- (3-Cyano-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-benzyl phenol) -8- (3-aminopyridinyl) Lysine-1-yl) -xanthine

 (205) 1- {2- [3- (aminol-propionyl) -pheninole] -2-oxo-ethyl} _3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiぺ lysin-1-inole) -xanthine (206) 1- {2- [3- (methylaminocarbonyl) -phenyl] -2-oxo-ethyl 3- 3-methyl-7- (2-methyl-5- Fluoro mouth benzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (207) 1- {2- [3- (Dimethylaminocarbonyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (208) 1- {2- [3- (methylsulfonyl) -pheninole] -2-oxo-ethyl} -3-methyl-7- (2-methinole-5-phenylene)-8 -(3-Aminopiperidine-1_yl) -Xanthine

(209) 1- {2- [3- (methylsulfinyl) -phenyl] -2-oxo-ethyl} -3-methyl-7— (2-methylinole 5_funoleo benzyl) -8- (3 -Aminopiperidine-1-yl) -Xanthine (210) 1_ {2-[3- (Methinoresnorehoeel) -Feninole]-2-oxo-ethyl}-3-Methinole-7- (2 -Methinole-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

(21 1) 1- [2- (3,5-dimethyl-phenyl) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopi Lysine-1-yl) -xanthine

(212) 1- [2- (3-Fluoro-5-methyl-phenyl) -2-oxo-ethyl] -3-methyl-7- ( 2-Methyl-5-fugleo benzoinole)-8- (3-aminopiperidine-1-yl) -xanthine

(213) 1- [2- (Pyridine-3-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole)-8- (3-α Minopiperidine-1-inole) -xanthine

 (214) 1- [2- (furan-2-inole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1 -Yill) -Xanthine

 (215) 1- [2- (thiophen-2-yl) -2-oxo-ethyl]-3-methyl-7- (2-methyl_5_fluorobenzyl) _8_ (3-aminopyridin-1-yl) -Xanthine

 (216) 1- [2- (Thiazol-2-inole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine-1- Inole) -xanthine

 (217) 1- [2- (thiazol-5-yl) -1-2-oxo-ethyl] -3-methinole-7- (2-methinole-5-fluorobenzyl) -8- (3-aminopyridin-1 -Yill) -Xanthine

 (218) 1- [2- (Thiazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (219) 1_ (2-phenyl-2-hydroxyimino-ethyl) -3-methyl-7- (2-methyl-5_fluorobenzizole) _8- (3-aminopiperidine-1-y Le) -xanthine

 (220) 1- (2-Phenyl-2- methoxyimino-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl ) -Xanthine

 (221) 1- (2-oxo-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) _8_ (3-aminopyridin-1-yl) -xanthine

 (222) 1- (2-oxo-butyl) -3-methinole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-ynole) -xanthine

 (223) 1- (3-methyl-2-oxo-butyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (224) 1- (2-cyclopropyl-2-oxo-ethynole) -3-methyl-7- (2-methynole-5-fluorobenzinole) -8- (3-aminopiperidine-1-inole) ) -Xanthin

 (225) 1- (2-cyclohexyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl ) -Xanthine

(226) 1- (3-dimethylamino-2,3-dioxo-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl)- Xanthine (227) 1- [3- (Pyridine-1-inole) -2,3-dioxo-propyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3 -Aminopiperidine-1-yl) -Xanthine

 (228) 1- (2-Pheninole-2-hydroxy-ethyl) -3-methylinole-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidine-1-yl) -Xanthine

 (229) 1- (2-Phenol-2-hydroxy-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -Xanthine

 (230) 1- (2-Phenyl-2-methoxy-ethyl) -3-methyl-7- (2-methyl_5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (231) 1-[(Quinazoline-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (232) 1-[(5-Methyl-isoxazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1- Yl)-xanthine

 (233) 1-[(oxazol-2-ynole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-(3-aminopiperidine-1-yl)- Xanthine

 (234) 1-[(1H-indazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3-aminopiperidin-1-yl ) -Xanthine

 (235) 1-[(5-fluoro-benzo [d] isothiazole-3-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine- 1-yl) -xanthine

(236) 1-[(5-Fluoro-benzo [d] isoxazole-3-inole) methinole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridinidine- 1-yl) -xanthine

(237) 1-[(5-Methyl-benzo [d] isoxazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridinidine- 1-inole) -xanthine

 (238) 1-[(5-Methyl-benzo [d] isothiazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-inole) -xanthine

 (239) 1- (2-cyclohexyl-ethyl) -3-methyl-7- (2-methynole-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -Xanthine

 (240) 1_ [2- (2-difluoromethoxy-phenyl) -ethynole] -3-methyl-7- (2-methynole-5-fluorobenzyl)-8- (3-aminopiperidine-tolyl) -xanthine

(241) 1- [2- (2-Difluoromethoxy-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-Methynole-5-phenolic benzyl)-8- (3-aminopiperidine-1-yl) -xanthine

(242) 1- [2- (2-Trifluoromethoxy-phenyl) -2-oxo-ethynole] _3-methyl-7- (2-methyl-5-fluorobenzinole) -8- (3- Aminopiperidine-1-yl) -xanthine

(243) 1- [2- (indan-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8_ (3-aminopyridin-1 -Yill) -Xanthine

 (244) 1- [2- (Benzo [1,3] dioxol_4_yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3- Amaminobiperidine-1-yl) -xanthine

(245) 1- [2- (2,2-Difluoro mouth-benzo [1,3] dioxol-4-yl)-2_oxo-ethynole] -3-methinole-7- (2-methyl-5 -Funoleo benzoinole) -8- (3-Aminopiperidine-1-yl) -Xanthine

 (246) 1- [2- (Naphth_1_yl) -2_oxo-ethyl] -3- 3-Methinole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (247) 1- [2- (2-isopropyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

 (248) 1- [2- (2-cyclopropyl-fuel) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (249) 1-[2_ (2-cyclopentyl pentinole) 3-aminopyridin-1-yl) -xanthine

 (250) 1-[2- (2-Fenyl-pheninole) -2-oxo-ethyl] -3-methinole 7- (2-methyl-5-fluorobenzyl) -8- (3-amino Piperidine-1-yl) -xanthine

 (251) 1_ [2- (2-cyclopentylmethoxy-pheninole) -2-oxo-ethynole] -3-methyl-7- (2-methinole-5-fluorobenzyl)-8- (3- Aminopiperidine-1-inole) -xanthine

(252) 1- (3-Phenyl-2-oxo-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl) -xanthine

 (253) 1- (3-Phenyl-3-oxo-propynole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (254) 1- [2- (2-Methylamino-phenyl) -2-oxo-ethyl] -3-Methyl_7- (2-Methynole-5-fluorobenzyl) -8- (3-Aminopiperidine-1- Yl) -xanthine

(255) 1- {2- [2- (N-cyanomethyl-N-methyl-amino) -phenyl] -2-oxo-ethyl } -3-Methyl-7- (2-methinole-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (2 5 6) 1 [2- (2-Cyanomethylamino-phenyl) -1-2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- ( 3-Aminopiperidine-1-inole) -xanthine (2 5 7) 1- (2- {2 _ [(methoxycarbol) methylamino] -phenyl} -2-oxo-ethyl) -3-methyl-7 -(2-Methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (25 8) 1_ [2- (2-Methylsulfonylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-(3- Aminopiperidine- 1-isle) -xanthine (25 9) 1- [2- (3-Methylamino-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5 -Fluoro mouth benzyl) -8- (3-Aminopiperidine_1-inole) -xanthine

 (260) 1- {2- [3- (N-cyanomethyl-N-methyl-amino) -phenyl] -2-oxo-ethyl} -3-methyl-7_ (2-methyl-5-fluorobenzyl)- 8_ (3-aminopyridin-1-inole) -xanthine

 (26 1) 1- (2- {3-[(dimethylamino) sulfonylamino] -phenyl} -2-oxo-ethyl) -3-methinole-7- (2-methinole-5-funoleo-benzyl ) -8- (3-Aminopiperidine-1-inole) -xanthine

 (26 2) 1- (2- {3-[(morpholine-4-inole) sulfonylamino] -phenyl} -2-oxo-ethyl) -3-methinole 7- (2-methyl-5-fluorobenzyl) ) -8-(3-Aminopiperidine-Toile)-Xanthine

 (26 3) 1- [2- (3-Aminosulfo-lamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopi Lysine-1-yl) -xanthine

(264) 1- [2- (3-Ethylsulfonylamino-phenyl) -2-oxo-ethyl] -3- 3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3 -Aminopiperidine-1 -isle) -xanthine (265) 1- [2- (3-Isopropylsulfonylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2 -Methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-yl) -Xanthin

(266) 1- {2- [3- (2-oxo-imidazoline-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl ) -8-(3-aminopyridin-1-yl) -ki Sanchin

 (267) 1- {2- [3- (3-Methyl-2-oxo-imidazolidine-1-inole) -fuel] -2-oxo-ethyl} -3-methinole-7- (2-methyl- 5-Fluorobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (268) 1- {2- [3- (3-Methyl-2,5-dioxo-imidazolidin-1-yl) -phenyl] -2-phenyl-oxo-ethyl 3-methyl-7- (2-methyl -5-Fluoro mouth benzyl) -8- (3-Aminopiperidin-1-yl) -Xanthine

 (269) 1--[3- (3-Methyl_2,4-dioxo-imidazolidine-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5 -Fluorobenzyl) -8- (3-aminopiperidin-1-yl) -xanthine

 (270) 1_ [(1-Methyl-2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methylen-7- (2-methyl-5-fluorobenzinole) -8- (3-Aminopyridine-1-yl) -xanthine (271) 1-[(2-oxo-1,2-dihydro-quinazoline-4-yl) methyl] -3-methyl-7- (2-Methyl-5-fluorobenzyl)-8- (3-aminopyridin-1-yl) -xanthine

 (272) 1-[(1-Methyl-2-oxo-1,2-dihydro-quinazoline-4-inole) methyl] -3--3-methyl-7_ (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-inole) -xanthine

 (273) 1-[(2-Cyano-naphthalene-1-yl) methinole] -3-methyl-7- (2-methyl-5-phenolobenzyl)-8- (3-aminopyridin-1-yl) Le) -xanthine

 (274) 1 _ [(6-cyano-naphthalene-1-inole) methyl] -3-methinole-7- (2-methyl-5-phenolobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

 (275) 1-[(5-cyano-naphthalene-1-ynole) methyl] -3-methyl-7- (2-methyl-5-phenololobenzinole) -8- (3-aminopiperidine- 1-Inole) -Xanthine

 (276) 1 [(8-Methyl-isoquinoline-1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl)- Xanthine

 (277) 1-[(5-cyano-isoquinoline-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- (3-aminopiperidine-1-yl ) -Xanthine

(278) 1-[(5-Aminocarbonyl-isoquino-V-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridinyl- 1-yl) -xanthine (279) 1-[(5-Aminosulfonyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (280) 1 _ [(5-Methylsulfonyl-isoquinoline-1-yl) methinole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

 (281) 1-[(5-Methylsulfo-lamino-isoquinolin-1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole)-8- (3-aminopiperidine-1 -Yill) -Xanthine

(282) 1-[(5-Methoxy-isoquinoline-1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (283) 1-[(6-Methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole ) -Xanthin

 (284) 1 _ [(7-Methylsulfonylamino-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl)-xanthine

(285) 1-[(7-cyano-isoquinoline-toyl) methyl] -3-methyl-7- (2-methyl-5-benzyl phenol) -8- (3-aminopiperidin-1-yl)- Xanthine

 (286) 1-[(7-aminoaminocarbonyl-isoquinoline-1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

 (287) G [2- (2-aryloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3 -Aminopiperidine-1-inole) -xanthine

 (288) 1- [2- (3-{[(morpholin-4-yl) carbonyl] methoxy} -phenyl) -2-oxo-ethyl] _3-methyl-7- (2-methyl- 5-Fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

 (289) 1- [2- (3-Carboxymethoxy-phenyl) -2-oxo-ethynole] -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine- 1-yl) -xanthine

(290) 1- [2- (3-Methylsulfonylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopi Perysin-1-yl) -xanthine

(291) 1- [2- (3-Methylsulfinylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3 -Aminopiperidine-1-yl) -Xanthine (292) 1- [2_ (3-Methylsulfonylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- ( 3-aminopyridin-1-yl) -xanthine

 (293) 1- [2- (2-oxo-2,3-dihydro-benzoxazol-4-yl) -2-oxo-ethyl] -3-methinole-7- (2-methyl- 5-Fluorobenzinole) -8- (3-aminopyridin-1-yl) -xanthine

 (2994) 1- [2- (2-oxo-2,3-dihydro-1H-benzoimidazonole-4-yl) -2--2-oxo-ethyl] -3-methyl- 7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine_1-inole) -xanthine

 (295) 1- [2_ (1-Methyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-inole) -2-oxo-ethynole] -3-methyl-7- ( 2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-ynole) -xanthine

 (299) 1- [2- (1,3-Dimethinole-2-oxo-2,3-dihydro-1H-benzoimidazole-4-yl) -2-oxo-ethyl] -3-methyl -7- (2-Methyl-5-fluorobenzyl) -8- (3-Aminopiperidin-1-yl) -xanthine

 (2 9 7) 1_ [2- (1H-Benzimidazol-4_yl)-2-oxo-ethyl]-3-Methynole-7- (2-Methynole-5-fluorobenzyl)-8- (3- Aminopiperidine-1-yl) -xanthine

 (2998) 1- [2- (2-Methyl-1H-benzoimidazole-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-inole) -xanthine

 (299) 1- [2- (Benzoxazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-α Minopiperidine-1-yl) -xanthine

 (300) 1- [2- (2-Methinole-benzoxazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-yl) -xanthine (301) 1- [2- (3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine-5- 2- (2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

(3 0 2) 1-[2- (Benzo [1,3] dioxole-4-inole) -2-oxo-ethyl] -3-methyl-7-(2-methyl-5-fluorobenzyl) -8 -(3-aminopiperidine-1-yl) -xanthine (303) 1- (1-Methoxycarbonyl-1-phenyl-2-methyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-y Le) -xanthine

 (304) 1- (1-carboxy-1-phenyl-methyl) -3-methyl-7- (2-methyl-5-fluoromouth benzyl) -8- (3-aminopyridin-1-yl ) -Xanthine

 (305) 1- (1-Aminocarbonyl-1-phenyl-methyl) -3-methylinole-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) -Xanthin '

 (306) 1- (1-Methoxycarbonyl-2-phenyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole)- Xanthine

 (307) 1- (1_carbonyl-2-phenyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1-yl)- Xanthine

 (308) 1_ (1-aminocarbonyl-2-phenyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl) -xanthine

 (309) 1-[(Benzofuran-2-yl) methyl] _3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1-inole) -xanthine

 (310) 1-[(2,3-Dihydro-benzofuran-2_yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridinidine-1 -Yill) -Xanthine

 (31 1) 1- [2- (2-Amino-3-3-cyano-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3 -Aminopiperidine-1-inole) -Xanthine

 (312) 1- [2- (2-Amino-3-fluoro-pheninole) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- ( 3-Aminopiperidine-1-yl) -xanthine

 (313) 1- (1-Methynole-2-phenyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl)-xanthine

 (314) 1- [2-oxo-2- (3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine-8-yl) -ethyl] -3-methylinole-7_ (2- Methinole-5-fluorobenzyl) -8- (3-aminopiperidin-1-yl) -xanthine

 (315) 1- [2-oxo-2- (4-methyl-3-oxo-3,4-dihydro-2H-benzo [1,4] oxazin_8-yl) -ethyl] -3-methyl -7- (2-Methyl-5-fluorobenzyl) -8- (3-Aminopiperidin-1-yl) -Xanthine

(316) 1-[(2-oxo-2H-couphenyl-4-yl) methyl] -3-methyl-7- (2-methyl-5-f Fluorobenzyl) -8- (3-aminopiperidine-1-yl) -xanthine

(317) 1-[(1-Oxo_1,2-dihydro-isoquinolin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine -1-yl) -xanthine (318) 1-[(2-Methyl_1-oxo-1,2, -dihydro-isoquinolin-4-yl) methyl] _-3 -methyl_7_ (2-methyl-5-fluorobenzyl) ) -8- (3-Aminopiperidine-1-inole) -xanthine

 (319) 1-[(4-oxo-3,4-dihydro-phthalazine-1-ynole) methyl] -3_methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine- 1-yl) -xanthine

 (320) 1-[(3-Methyl-4-oxo-3,4-dihydro-phthalazine-1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- ( 3-Aminopiperidine-1-yl) -xanthine

 (321) 1-[([1,5] naphthyridin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole)-8- (3-aminopiperidine-1- Inore)-xanthine

 (322) 1-[([1,7] Naphthyridin-8-yl) methyl] _3-methyl_7- (2-methyl-5-fluorobenzyl) -8- (3-aminopiperidine-1 -Yill) -Xanthine

 (323) 1-[(quinolin-2-inole) methyl] -3-methinole-7- (2-methinole-5-fluorobenzyl) -8- (3-aminopyridin-1-yl)- Xanthine

 (324) 1-[(Isoquinoline-3-inole) methinole] -3-methyl-7- (2-methyl_5-fluorobenzene) -8- (3-aminopyridin-1-yl) -xanthine

 (325) 1- {2-oxo-2_ [3- (2-oxo-tetrahydro-pyrimidine-1-yl) -phenyl] -ethyl} -3-methyl-7- (2-methyl_5-fluorobenzyl ) -8- (3-Aminopiperidine-1-yl)-xanthine

 (326) 1- {2-oxo-2- [3- (3-methyl-2-oxo-tetrahydro-pyrimidine-1-yl) -pheninole] -ethyl} -3-methyl-7- (2 -Methyl-5-fluorobenzinole) -8- (3-Aminopiperidine-1-yl) -xanthine

 (327) 1- (2-Phenyl-2-oxoethyl) -3-methyl-7- (2-chloro-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) xanthine

(328) 1- (2-Phenyl-2-oxoxenole) -3-methyl-7- (2-promo-5-phenylene-benzoyl)-8- (3-aminopyridin-1-yl) xanthine (32 9) 1-[(Isoquinoline-1-yl) methyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8- (3-aminopyridin-1-yl Le) -xanthine

 (330) 1-[(Isoquinolin-1-yl) methyl] -3-methyl-7- (2-bromo-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) ) -Xanthine

 (3 3 1) 1- [2- (Pyridin-2-ynole) ethyl] -3-Methynole-7- (2-methyl-5-fluorobenzyl) -8- (3-Aminopiperidine-1-yl) -Xanthine

 (3 3 2) 1- [2- (Pyridin-2-inole) ethyl] -3-Methinole-7- (2-chloro-5-fluorobenzyl) -8- (3-Aminopiperidine-1-y Le) -xanthine

 (3 3 3) 1- [2- (pyridin-2-yl) ethyl] -3-methyl-7- (2-bromo-5_fluoromethylbenzyl) -8- (3-aminopiperidine-1 -Yl) -Xanthine

 (334) 1- [2- (2-naphthyl) ethyl] -3-methyl-7- (2-c-mouth-5-fluorobenzyl)-8- (3-aminopyridin-1-yl)- Xanthine

 (3 3 5) 1- [2- (2-Naphthinole) ethyl] -3-methyl-7- (2-promo-5-fluorobenzinole) -8- (3-Aminopiperidine-1-yl) -Xanthine

 (3 3 6) 1- (2-phenyl-2-oxoethyl) -3-methyl-7- (2-chloro-5-funenole-benzizole) -8- (3-aminopiperidine-1- (Inole) -xanthine

 (3 3 7) 1- (2-Pheninole-2-oxoethyl) -3-methinole-7- (2-Bromo-5-Fenoleo-benzyl) -8- (3-Aminopyridine-1-yl) -Xanthine

 (3 38) 1- [2- (2-Methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-oct-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl)-xanthine

 (33 9) 1_ [2- (2-methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-promo-5-fluorobenzyl) -8- (3-aminopiperidine-tolyl)- Xanthine

 (340) 1- [2- (3-Methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-kuguchi-5-fluorobenzyl) -8- (3-aminopyridin-1 -Inole) -Xanthine

 (34 1) 1- [2- (3-Methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-promo-5-fluorobenzyl) -8- (3-aminopiperidine-1- Yl)-xanthine

 (342) 1- [2- (2-Chlorophenyl) -2-oxotinole] -3-methinole-7- (2-coulo-5-fluorobenzyl) -8- (3-aminopiperidine-1-y Le) -xanthine

(343) 1- [2- (2-Chlorohexyl) -2-oxoethyl] -3-Methyl-7- (2-Bumo-5-f Norobenzyl) -8- (3-aminopyridin-1-yl) -xanthine

 (344) 1- [2- (3-Chlorophenyl) -2-oxo-ethyl] -3-methyl-7- (2-co-mouth_5 -fluoro-benzinole) -8- (3-Aminopiperidine-1 -Yill) -Xanthine

 (345) 1- [2- (3-Chlorophenyl) -2_oxoethyl] -3-methynole-7- (2-bromo-5-fluorobenzyl) -8- (3-aminopyridin-1-y Le) -xanthine

 (346) 1- (2-phenylethyl) -3-methyl-7- (2-chloro-5-fluorobenzyl) -8- (

3-Aminopiperidine-1-inole) xanthine

 (347) 1- (2-phenylethyl) -3-methinole-7_ (2-bromo_5_fluorobenzinole) -8- (3-aminopiperidine-1-inole) xanthine

 (348) 1- [2- (2-Promopheninole) -2-oxoethyl] -3--Methinole-7- (2-Methinole-5-fluorobenzyl)-8- (3-Aminopiperidine-1-y Le) xanthine

 (349) 1- [2- (2-Cyanophenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) — 8- (3-Aminopiperidine- 1-inole) xanthine

 (350) 1- [2- (2-Methoxyphenyl) -2-oxoxethyl] -3-methyl-7_ (2-methyl-5-fluoromethylbenzyl) -8- (3-aminopyridin-1- Inole) Xanthine

 (35 1) 1_ [2- (3-Methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- (3-aminopyridin-1_y X) Xanthine In the above compounds (1) to (351), a piperidine compound in which the 3-amino group of 3-aminobiperidine has an absolute configuration represented by the following formula (C) is more preferable.

また、 本発明のキサンチン化合物の好ましい例として、 下記のシクロアルカンジ ァミン化合物も例示出来る。

Preferred examples of the xanthine compound of the present invention include the following cycloalkanediamine compounds.

(352) 1,3-dimethyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine (353) 1,3-Dimethyl_7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (354) 1,3-dimethyl-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (355) 1- [2- (phenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexynole) amino] xanthine

 (356) 1- [2- (2-fluorophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (357) 1- [2- (2-Chlorophenyl) ethyl] _3_methyl_7_ (2-Methyl-5-fluorobenzyl) -8-[(2-Aminocyclohexyl) amino] xanthine

 (358) 1- [2- (2-Bromophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (359) 1- [2- (2-Cyanophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminoaminohexyl) amino] xanthine

 (360) 1- [2- (2-Methoxyphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexanol) amino] xanthine

 (36 1) 1- [2- (3-fluorophenyl) ethyl] -3-methyl-7- (2-methinole-5-fluorobenzinole) -8-[(2_aminocyclohexynole) amino] Xanthine

 (362) 1- [2- (3-Chlorophenethyl) ethyl] -3-methyl-7- (2-methyl-5-phenylol benzyl)-8-[(2-aminohexylhexamino) amino ] Xanthine

 (363) 1- [2- (3-Bromophenyl) ethynole] -3-methyl-7- (2-methyl-5-phenolic benzyl) -8-[(2-aminocyclyl hexinole) amino] Xanthine

 (364) 1- [2- (3-Cyanophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (365) 1- [2- (3-Methoxyphenyl) ethyl] -3-methyl_7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (366) 1- [2- (Phenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2_aminocyclohexyl) amino] xanthine

(367) 1_ [2- (2-fluorophenyl) 2 2-oxoethyl] -3-methyl-7- (2-methynole-5- Fluoro mouth benzyl) -8-[(2-aminocyclohexyl) amino] xanthine

(368) 1- [2- (2-Chlorophenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexamino) amino ] Xanthine

 (369) 1- [2- (2-Bromophen-nore) -2-oxo-cinnole] -3-Methinole-7- (2-Methinole-5-phenylolbenzyl) -8-[(2_aminocyclohexyl) amino ] Xanthine

 (370) 1- [2- (2-Cyanophenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminohexanol) amino] xanthine

 (371) 1_ [2_ (2-methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methynole-5-benzoyl benzyl)-8-[(2-aminocyclyl hexinole) amino] Xanthine

 (372) 1-[2- (3-Fluorinole) -2- oxoechinole] -3 -Methinole-7- (2-Methinole-5-fluorobenzyl) -8-[(2-aminohexylhexyl) Amino] xanthine

 (373) 1- [2- (3- (3-octaphenyl) -2-oxoethyl] -3-methyl-7- (2-methynole-5-phenol-benzinole)-8- [(2-aminocycloto Xinole) amino] xanthine

 (374) 1- [2- (3-Bromophenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminohexyl) amino] xanthine

 (375) 1- [2- (3-Cyanophenyl) -2-methyl--3-methyl-7- (2-methyl-5-phenolobenzyl) -8-[(2-aminohexanol) amino ] Xanthine

 (376) 1- [2- (3-Methoxyphenyl) -2-oxo-ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] Xanthine

 (377) 1- (Methoxycarbonylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexinole) amino] xanthine

 (378) 1- (ethoxycarboeylmethyl) -3-methyl-7- (2-coguchi-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (379) 1-Methyl-3- (methoxycarbolmethyl) -7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclohexyl) amino] xanthine

 (380) 1-methyl-3- (ethoxycarbonylmethyl) -7- (2-chloro-5-fluorobenzyl) _8-[(2-aminocyclohexyl) amino] xanthine

(381) 1- (3-Phenylpropynole) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclohexynole) amino] xanthine (38 2) 1- (2-hydroxyethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexyl) amino] xanthine

 (3 83) 1- (2-Methoxyethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (384) 1- [2- (Dimethylamino) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (38 5) 1- [2- (2,4,6-trimethylphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl ) Amino] xanthine

 (3 8 6) 1- [2- (2,4-Dichrophenyl) ethyl] _3-Methinole-7- (2-methyl-5-fluorobenzyl) _8-[(2-Aminocyclohexyl) amino ] Xanthine

 (38 7) 1- (2-thiophen-2-ynole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (388) 1- (2-Thiophene-3-inole) -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminohexanol) amino] xanthine

 (38 9) 1- [2- (4-tert-butylphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluoro-benzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

 (3 90) 1- [2- (2-fluorophenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzy / le) -8-[(2-aminocyclohexyl) Amino] xanthine

 (3 9 1) 1- [2- (2-methylphenyl) ethyl] _3-methyl-7_ (2-methyl-5-fluorobenzene)-8-[(2-aminocyclylhexyl) amino] xanthine

 (3 92) 1_ [2- (3-methylphenyl) ethyl] _3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] xanthine

 (3 9 3) 1- [2- (1-naphthyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (3 94) 1- [2- (2-Naphthinole) ethyl] _3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (3 95) 1- (4-Phenylbutyl) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclylhexynole) amino] xanthine

(3 96) 1_ [2- (3-trifluoromethylphenyl) ethyl] -3-methyl-7— (2-methyl-5 -Fluorobenzyl)-8-[(2-aminocyclohexyl) amino] xanthine

 (397) 1- [2- (Pyridin-2-inole) ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -1-8-[(2-aminocyclohexyl) amino] Xanthine

 (398) 1- [2- (Pyrrol-1-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobendinole) -8-[(2-aminocyclohexanol) amino ] Xanthine

 (399) 1- [2-([1,2,3] triazol-1-inole) ethyl] -3-methinole-7- (2-methyl-5-fluorobenzyl) -8 _ [(2-aminocyclohexanol ) Amino] xanthine

 (400) 1- [2- (pyridine-4-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobendinole) -8-[(2-aminocyclohexyl) amino] xanthine

 (401) 1- (3-Butene-1-inole) -3-methyl-7- (2-methinole-5-fluorobenzyl) -8-[(2-aminohexylhexanol) amino] xanthine

 (402) 1- (4-Pentin-1-yl) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (403) 1- [2- (4-Methinolethiazole-5-yl) ethyl] -3-methinole-7- (2-methyl-5-phenolobenzyl) -8-[(2_aminocyclohexyl ) Amino] xanthine

 (404) 1- [2- (3-Promophenyl) ethynole] -3-Methynole-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclylhexyl) amino] xanthine

 (405) 1- [2_ (3-Mouth-phenyl) ethyl] -3-methinole-7- (2-methyl-5-phenyl-henylo) -8-[(2-aminocyclohexynole) amino] Xanthine

 (406) 1-((E) -2-Fenylvinyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 _ [(2_aminocyclohexyl) amino] xanthine

 (407) 1 [2— (2-c-mouth feninole) etino-le] —3-methino- 7- (2-methyl-5-benzole benzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

 (408) 1- [2- (2-Trifluoromethylphenyl) ethyl] -3--3-methinole-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (409) 1- [2- (2-bromophen-ethyl) ethyl] -3-methynole-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexynole) amino] Xanthine

(410) 1- [2- (3-Fluorophenole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine (4 1 1) 1_ [2- (3-nitrophenyl) ethyl]-3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclohexyl) amino ] Xanthine

 (4 1 2) 1- [2- (4-Methylphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole)-8-[(2-aminocyclohexynole) amino] xanthine

 (4 13) 1- [2- (4-Hydroxypheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexinole ) Amino] xanthine

 (4 14) 1- [2- (3-hydroxypheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino ] Xanthine

 (4 15) 1_ [(Methoxycarbonyl) methyl] -3-Methynole-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexyl / re) amino] xanthine

 (4 16) 1- [2- (Methoxycarbinole) ethyl] -3-methinole-7- (2-methyl-5_fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (4 17) triphenyl-3_methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexyl) amino] xanthine

 (4 1 8) 1- [2- (3,5-diphenylenoethyl) ethyl] -3-methinole-7- (2-methyl-5-phenolyl benzyl) -8-[(2-aminocyclyl Mouth hexinole) amino] xanthine

 (4 1 9) 1- [2- (2,6-difluoropheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzizole) -8-[(2-aminocyclohexyl) Amino] xanthine

 (420) 1- [2- (thiophen-3-yl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclohexyl) amino ] Xanthine

 (42 1) 1- [2- (3-Cyanometooxyphenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino ] Xanthine

 (422) 1- [2- (3-benzyloxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl ) Amino] xanthine

 (423) 1- [2- (3-Phenylsulfo-phenyloxy) -2--2-oxoethyl] _3-methyl-7- (2-methyl-5-fluoro benzyl) -8- [(2-aminosic Xyl) amino] xanthine

(424) 1- [2- (3-hydroxyphenyl) -2-oxoethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino ] Xanthine (425) 1_ [2- (3,5-dimethoxyphenyl) ethyl] -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

 (426) 1_ [3- (Methoxycarbol) propyl] _3-Methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-Aminocyclohexanol) amino] xanthine

 (427) 1- {2- [4- (ethoxycarbonyl) phenyl] ethyl} -3-methyl-7_ (2-methyl-5-fluorobenzyl) -8-[(2-aminohexanol) amino] xanthine

 (428) 1- (phenylsulfanylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzene / re)-8-[(2-aminocyclohexyl) amino] xanthine

 (429) 1- (phenylsulfiermethyl) -3-methinole-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (430) 1- (2-Methoxycarbonyl-2-propene_1-yl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (431) 1-[(Pyridin-2-yl) methinole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (432) 1- [2- (3-Fenyloxy-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-phenylphenol) -8-[(2 -Aminoxyhexyl) amino] xanthin

(433) 1- [2- (3-Amino-phenyl) -2-oxo-ethyl] -3-Methyl-7- (2-methyl_5-fluorobenzinole)-8-[(2-aminocyclyl Hexyl) amino] xanthine

 (434) 1- (2- {3- [bis (methanesulfonyl) -amino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 -[(2-aminohexyl)] xanthine

 (435) 1- [2- (2-Promo-5-dimethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8- [(2-aminocyclylhexyl) amino] xanthine

 (436) 1- [2- (3-Nitro-phenyl) -2-oxo-ethynole] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclyl Mouth hexinole) amino] xanthine

(437) 1- [2- (3-Methoxycarbonylamino-phenyl) -2_oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2- Hexamino) amino] xanthin (438) 1- [2- (3-Acetylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 _ [(2-aminocyclohexyl) amino ] Xanthine

(439) 1- [2- (3-{[(Ethoxycarbonylamino) carbonyl] amino} -phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluoro Mouth benzinole) -8-[(2-aminocycline hexinole) amino] xanthin

 (440) 1- [2- (3-cyanomethylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Hexyl) amino] xanthin

(441) 1-[(thiazonole-2-yl) methinole] -3- 3-methinole-7- (2-methinole-5-benolene benzole) -8 _ [(2-aminocyclohexyl) amino] xanthin

 (442) 1_ [(isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexynole) amino] xanthine

 (443) 1-[(Isoquinolin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexynole) amino] xanthine

 (444) 1-[(Benzo [d] isothiazole-3-yl) methyl] -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2-aminoaminohexyl) amino] xanthine

 (445) 1-[(Benzo [d] isoxazoinole-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) Amino] xanthine

 (446) 1-[(Pyridin-3-yl) methyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (447) 1-[(Pyridin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (448) 1-[(isoxazole-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] xanthine

 (449) 1-[(1-Naphthyl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (450) 1-[(Aminocarboyl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminohexamino) amino] xanthine

(451) 1-[2_ (3-Methanesulfonylamino-phenyl) -2-oxo-ethyl] -3-methylen-7- (2-methyl-5-fluorobenzyl)-8-[(2- Aminosic hexinole) amino] xane Chin

 (452) 1— [2- (2-Nitro-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) _8- [(to the 2-aminocyclide Xyl) amino] xanthine

 (453) 1- [2- (2-Amino-phenyl) -2-oxo-ethyl] -3- 3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclyl Hexyl) amino] xanthin

 (454) 1- [2- {3_ [(methylamino) thiocarbonylamino] -phenyl} -2_oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminocyclohexanol) amino] xanthine

 (455) 1_ [2- (2-Acetylamino-phenyl)-2-oxo-ethyl]-3_methyl _7_ (2-methyl-5-fluoro-benzyl)-8- [(2-aminocyclohexyl) ) Amino] xanthine

(456) 1-[(6-Methyl-pyridine-2-inole) methyl] -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (457) 1 _ [(1-Methyl-1 H-indazol-3-yl) methyl] -3-methyl-7- (2-methyl_5_fluorobenzyl)-8-[(2-aminosic Xyl) amino] xanthine

 (458) 1- (2- {3-[(Methoxycarbonyl) methylamino] -phenyl} _2-oxo-chinole) -3-methinole-7- (2-methinole-5-fluorobenzyl)- 8- [(2-aminohexanol) amino] xanthine

 (459) 1-cyanomethyl-3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexanol) amino] xanthine

 (460) 1- [2- (2-Hydroxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl hexinole ) Amino] xanthine

 (461) 1- [2- (2-Methanesnorphoenole-Feninore) -2-oxo-ethyl] -3-Methyl-7- (2-Methyl-5-fluorobenzyl)-8-[(2- Aminocyclohexamino) amino] xanthine (462) 1- [2- {2-[(Methoxycarbol) methoxy] -phenyl} -2-oxo-ethyl] -3-methyl-7- (2 -Methyl-5-fluorobenzyl) -8-[(2-aminohexyl) amino] xanthine

(463) 1- [2- (2-cyanomethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl)-8-[(2-aminohexylhexyl) Amino] xanthine (464) 1- (2- {3-[(Methylaminocarbo-nore) methoxy] -phenyl} -2-oxo-e Tyl) -3-Methyl-7- (2-methynole-5-fluorobenzinole)-8-[(2-aminohexylhexyl) amino] xanthine

 (465) 1- (2- {3-[(Aminocarbonyl) methoxy] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 -[(2-aminohexanol) amino] xanthine

 (466) 1- (2- {3-[(Dimethylaminocarbonyl) amino] -phenyl} -2-oxo-ethyl) -3-methyl-7_ (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminohexyl) amino] xanthine

 (467) 1- (4-oxo-4H-coucum-3-yl) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(to the 2-amino amino acid mouth Xinole) amino] xanthine

 (468) 1-[(3-Methyl-pyridine-2-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino ] Xanthine

 (469) 1-[(5-Methyl-pyridin-2-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminohexanol) amino ] Xanthine

 (470) 1-[(4-Methyl-pyridin-2-yl) methyl] -3-methyl_7_ (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (471) 1-[(quinolin-4-yl) methyl] _3_methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexanol) amino] xanthine

 (472) 1-[(quinolin-8-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzoyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (473) 1-[(5-Nitro-isoquinoline_1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (474) 1-[(2-oxo-1,2-dihydro-quinolin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-amino Cyclohexyl) amino] xanthine (475) 1-[(5-Amino-isoquinoline-1-yl) methyl] -3-methyl-7- (2-methyl_5_fluorobenzinole) -8-[( 2-aminoaminohexyl) amino] xanthine

 (476) 1- [2- (3-Aminosulfoninole-phenyl) -2-oxo-ethyl] -3--methinole-7- (2-methyl-5-fluorobenzyl) -8-[(2- Aminocyclohexyl) amino] xanthin

(477) 1- (2-phenoxy-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole ) -8-[(2-Aminohexylhexamino) amino] xanthine

 (478) 1-potoxymethyl-3-methinole-7- (2-methyl_5_fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (479) 1- (3-Carboxy-propyl pill) -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (480) 1- [2- (4-Carboxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8 _ [(2-aminocyclohexyl) amino] xanthine

 (481) 1- (2-Phenyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (482) 1- [2- (3-Amino-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexinole) Amino] xanthine

 (483) 1- [2- (Pyrrolidine-1-1-inole) ethynole] -3- 3-Methinole-7- (2-methyl-5-phenylphenol) -8-[(2-aminohexylhexamino) amino ] Xanthine

 (484) 1- [2- (Piperidin-1-yl) ethyl] -3-methinole-7- (2-methyl-5-fluorobenzinole)-8-[(2-aminocyclohexinole) amino ] Xanthine

 (485) 1-[2- (Morpholine-4-inole) ethyl]-3-Methyl-7- (2-methyl-5-fluorobenzinole)-8-[(2-aminocyclohexinole) amino] Xanthine

 (486) 1- [2- (Pyrazine-1-inole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole)-8-[(2-aminocyclylhexyl) Amino] xanthine

 (487) 1- [2- (4-Methyl-piperazine-1-yl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) _8 _ [(2-aminocyclohexanol) amino] Xanthine

 (488) 1- (3-Hydroxypropyl) -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (489) 1- (3-Methoxypropynole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (490) 1- (3-ethoxypropyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

(491) 1- [3- (Dimethylamino) propyl] _3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexinole) amino] xanthine (492) 1- [3- (pyrrolidine-1-yl) propyl] -3-methinole-7- (2-methinole-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] xanthine

 (493) 1- [3- (morpholin-4-ynole) propyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (494) 1- [3- (Piperazin_1-yl) propyl]-3-methyl-7- (2-methyl-5-fluorobenzene)-8-[(2-aminoaminohexyl) amino] xanthine

 (495) 1- [3- (4-Methyl-pyrazine-1-inole) propyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) _8-[(2-aminocyclyl Xyl) amino] xanthine

 (496) 1- (Pyrrolidine-1-yl-propanolmethyl) -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (497) 1- (Pyridin-1-yl-carbonylamino) -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclylhexyl / re) amino ] Xanthine

 (498) 1- (Morpholine-4-yl-carbonylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8 _ [(2-aminocyclylhexyl) amino] xanthine

 (499) 1- [2- (3-Fluoro-4-hydroxy-phenyl) -ethyl] _3-methyl-7- (2-methyl-5-fluorobenzyl) _8_ [(2-aminohexylhexamino) amino ] Xanthine

 (500) 1- [2- (4 methoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (501) 1- [2- (4-ethoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluoro-benzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

 (502) 1- (2- {4-[(carboxymethyl) oxy] -phenyl} -ethyl) -3-methyl-7 (2-methyl-5-fluorobenzyl) -8- [(2-aminocyclyl Hexyl) amino] xanthine

(503) 1- [2- (2-Fluoro-5-hydroxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2- Aminoc mouth hexinole) amino] xanthine

 (504) 1- [2- (3-Methoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluoro benzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

 (505) 1- {2- [3- (carboxymethyloxy) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoamino Hexyl) amino] xanthine

(506) 1_ (2-{3-[(ethoxycarbonyl) methyloxy] -phenyl} -ethyl) -3- Methyl _7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthin

 (507) 1- [2- (2-Hydroxy-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) _8-[(2-aminocyclohexinole) ) Amino] xanthine

 (508) 1- [2- (2-Methoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminohexylhexamino) amino ] Xanthine

 (509) 1_ {2- [2- (carboxymethyloxy) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Methylhexyl) amino] xanthine (510) 1- (2- {2 _ [(Methoxycarbonyl) methyloxy] -phenyl} -ethyl) -3-methyl-7- (2-methyl-5-fluoro Benzyl) -8-[(2-aminocyclylhexyl) amino] xanthin

 (51 1) 1_ [2- (4-hydroxymethyl-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl ) Amino] xanthine

 (512) 1- {2- [4- (Methoxycarbonyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- [(2-aminocyclyl Hexinole) amino] xanthin

 (513) 1- {2- [4- (carboxymethyl) -pheninole] -ethyl} -3-methyl-7- (2-methinole-5-fluorobenzinole) -8-[(2- Aminohexylhexyl) amino] xanthine

 (514) 1- (2- {4-[(Methoxycarbonyl) methyl] -fuyl} -ethyl) -3_methyl-7- (2-methyl-5-fluorobenzyl) -8-[( 2-Aminocyclohexyl) amino] xanthine (515) 1- {2- [4- (2-carboxy-ethyl) -phenyl] -ethyl} -3_methyl-7- (2-methyl-5- Fluorobenzyl) -8- [(2_aminocyclylhexyl) amino] xanthine

 (516) 1_ (2- {4- [2- (Methoxycarbonyl) -ethyl] -phenyl} -ethyl) -3-methylino-7- (2-methyl-5-fluorobenzyl)-8- [ (2-aminocyclylhexyl) amino] xanthin

 (517) 1- [2- (3-Methyl-furyl) -ethyl] -3-methylinole-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (518) 1- [2- (3-Feboxyl-phenyl) -ethyl] -3-Methyl-7- (2-methyl-5-phenol) Hexyl) amino] xanthine

(519) 1_ {2- [3- (ethoxycarbonyl) -phenyl] -ethyl} -3_methyl-7- (2-methyl Le-5-Fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (5 20) 1- {2- [3- (potoxymethyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminoamino Xyl) amino] xanthine

 (5 2 1) 1- (2- {3-[(Methoxycarbonyl) methyl] -f; π-el} -ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [ (2-aminoaminohexyl) amino] xanthine

(5 22) 1- {2- [3- (2-carboxy-ethyl) -furyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Hexyl) amino] xanthin

 (5 23) 1- (2_ {3- [2- (methoxycanolepo-noreth) -ethynole] -pheninole} -ethynole) -3-Methyl-7- (2-methyl-5-phenylphenol) -8-[(2-aminocyclohexanol) amino] xanthine

 (5 24) 1- [2- (2-Methyl-phenyl) -ethyl] -3-Methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexanol) amino] Xanthine

 (5 25) 1- [2- (2-Canololepoxy-Feninole) -Ethynole] -3-Methyl-7- (2-Methinole-5-Fenolerobenzyl) -8-[(2-aminocyclylhexyl) amino ] Xanthine

 (525) 1- {2- [2- (methoxycarbonyl) -phenyl] -ethyl} -3-methyl_7_ (2-methyl-5-fluorobenzyl) -8-[(2-aminohexyl hexinole) Amino] xanthine

 (5 27) 1- [2- (4-Fluoro-phenyl) -ethyl] -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Hexyl) amino] xanthine

 (5 28) 1- [2- (4-Chloro-phenyl) -ethyl] -3-methyl-7- (2-methyl_5_fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (5 29) 1- [2- (4-Bromo-pheninole) -ethyl] -3-methinole-7- (2-methinole-5-funoleno-benzinole)-8-[(2-aminocyclohexeneole) ) Amino] xanthine

 (5 30) 1- [2- (4-cyano-fuel) -ethyl] -3-methyl-7- (2-methyl_5_fluorobenzyl)-8-[(2-aminocyclohexyl) amino] xanthine

 (5 3 1) 1- [2- (4-Trifluoromethoxy-phenyl) -ethynole] -3-methynole-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl hexinole) Amino] xanthine

 (5 3 2) 1- [2- (4-Methylsulferyl-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminocyclyl Mouthhexyl) amino] xanthin

(5 3 3) 1- [2- (4-methylsulfinyl-phenyl) -ethyl チ ル -3-methyl-7- (2-methinole -5-Fluorobenzyl)-8 _ [(2-aminocyclylhexyl) amino] xanthine

 (534) 1- [2- (4-Methylsulfonyl-pheninole) -ethyl] -3-methyl-7- (2-methinole-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino ] Xanthine

 (53 5) 1- [2- (4-Trifluoromethyl-phenyl) -ethyl] -3-methyl_7_ (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) Amino] xanthine

 (5 36) 1— [2- (4-Amino-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) _8-[(2-aminocyclohexinole) Amino] xanthine

 (53 7) 1- (2- {4-[(methylcarbonyl) amino] -phenyltoethenole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminocyclyl Xinole) amino] xanthine (5 38) 1- (2- {4-[(methylsulfonyl) amino] -phenyl} _ethyl) _3_methyl-7- (2-methyl-5-fluoromethylbenzyl)- 8-[(2-aminocyclylhexyl) amino] xanthine

(5 3 9) 1- {2- [4- (aminocarbonyl) -phenyl] -ethyl} -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminocyclyl Xinole) amino] xanthin

 (540) 1- {2- [4- (methylaminocarbonyl) -phenyl] -ethyl 3-methinole-7- (2-methyl-5-fluorobenzinole)-8- [(2-aminosic Xinole) amino] xanthine

(54 1) 1- {2- [4- (Dimethylaminopropyl) -phenyl] -ethyl} -3-methyl-7- (2-methynole-5-fluoro-mouth benzyl) -8-[(2-aminoamino-mouth Hexyl) amino] xanthine

(542) 1- {2- [4- (Aminosulfonyl) -feninole] -ethyl} -3-methyl-7- (2-methinole_5_fluorobenzinole) -8 _ [(2-aminocycl Hexyl) amino] xanthin

 (543) 1- {2- [4- (Methylaminosulfonyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Xyl) amino] xanthine

(544) 1- {2- [4- (Dimethylaminosulfonyl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminoaminohexanol) ) Amino] xanthine

(545) 1- [3- (Ethoxycarbonyl) -propyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (546) 1- [2- (3,4-Dimethyl-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-phenolylbenzyl)-8-[(2-aminocyclylhexyl ) Amino] xanthine

(547) 1- [2- (2-Fluo-5-chloro-pheninole) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclyl Hexyl) amino] xanthin (548) 1- [2- (3,5-Dimethoxy-phenyl) -ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) Amino] xanthine

 (549) 1- [2- (Naphthalene-2-yl) -ethynole] -3-methinole-7- (2-methyl-5-phenylene benzyl) -8-[(2-aminohexylhexyl) amino ] Xanthine

 (550) 1- [2- (Pyridine-3_yl) -ethynole] -3-Methinole_7- (2-Methyl-5-funolethiol benzyl) -8-[(2-Aminoxyhexyl) Amino] xanthine

 (5 5 1) 1- [4-Phenyl-butyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl / re) amino] xanthine

 (5 5 2) 1_ (2-phenylsulfaninole-ethyl) -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (5 5 3) 1- (2-phenylsulfinyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (5 54) 1- (2-Phenylsulfonyl-ethynole) -3-Methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexinole) amino] xanthine

 (5 5 5) 1- [2- (3-Fluoro mouth-Feninole) -2-oxo-ethynole] -3-Methyl-7- (2-methyl-5_fluorobenzyl) -8 _ [(2_amino Cyclohexyl) amino] xanthin

 (5 56) 1- [2- (3-chloro-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-amino Cyclohexyl) amino] xanthin

 (5 5 7) 1- [2- (3-bromo-pheninole) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 _ [(2-aminocyclo Hexyl) amino] xanthine

 (5 58) 1- [2- (3-Methyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl ) Amino] xanthine

 (5 5 9) 1- [2- (3-trifluoromethyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl)-8-[(2_ Aminocyclohexyl) amino] xanthine (560) 1— [2- (2-methyl-phenyl) —2-oxo-ethyl] —3-methyl-7_ (2-methynole-5-fluorobenzyl) -8- [ (2-aminocyclohexyl) amino] xanthine

(56 1) 1- [2- (3-Difluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- '(2-methyl-5-fluorobenzyl)-8- [(2- Aminocyclylhexyl) amino] xanthine (5 62) 1- [2- (3-trifluoromethoxy-phenyl) -2-oxo-ethyl] -3-methyl- 7- (2-Methyl-5-fluorobenzyl) -8-[(2-aminohexyl) amino] xanthine

 (5 6 3) 1- [2_ (3-ethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methynole-5-fluoromethylbenzyl) -8 _ [(2-amino Cyclohexyl) amino] xanthin

 (5 64) 1- [2- (3-Isopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2- Aminohexylhexyl) amino] xanthine

(5 6 5) 1- [2- (3-cyclopropyloxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- [( 2-aminocyclohexyl) amino] xanthine

 (5 66) 1- [2- (3-cyclopentyloxy-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[( 2-aminoaminohexyl) amino] xanthine

 (5 6 7) 1- [2- (3-Cyclopropylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [ (2-aminocyclohexyl) amino] xanthine

 (5 6 8) 1- {2_ [3- (2,2,2-trifluoroethoxy) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexyl) hexamino] xanthine

 (5 6 9) 1- [2- (4-hydroxy-phen-ole) -2-oxo-ethyl] -3--3-methinole-7_ (2-methyl-5-fluorobenzyl)-8-[(2_ Aminohexylhexyl) amino] xanthine

 (570) 1- {2- [3- (Methylcarbonylamino) -phenyl] -2-oxo-ethyl} -3-methyl-6- (2-methyl-5_fluorobenzyl) -8- [(2-Aminocyclohexyl) amino] xanthine (5 7 1) 1- {2- [3- (aminocarbonylcarbonylamino) -fuunyl] -2-oxo-ethyl} -3-methyl-7 -(2-Methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthin

(5 72) 1- {2- [3- (Methylamino carbonylamino) -pheninole] -2-oxo-ethyl} -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2 -Aminoxy mouth hexyl) amino ] Xanthine

 (573) 1- {2- [3- (Dimethylaminopropyl-phenyl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methynole-5-fluorobenzyl) -8- [ (2-aminohexyl) amino] xanthine

 (574) 1- {2- [3- (methylsulfonylamino) -phenyl] -2-oxo-ethyl} -3-methylin-7- (2-methyl-5-fluorobenzyl) -8- [(2 -Aminoxyhexyl) amino] xanthin

 (575) 1- {2- [3- (aminosulfonyl) -phenyl] -2-oxo-ethyl} _3_methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Xyl) amino] xanthine (576) 1- {2- [3- (methylaminosulfoninole) -phenyl] -2-oxo-ethyl} -3-methylinole-7- (2-methyl-5-phenoleobenzyl )-8-[(2-aminoaminohexyl) amino] xanthin

 (577) 1- {2- [3- (dimethylaminosulfol) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2 -Aminosic hexyl) amino] kisanthin

 (578) 1- [2- (3-ethyninole-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclyl Xyl) amino] xanthine

 (579) 1- [2- (3-Cyan-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Xinole) amino] xanthin

 (580) 1-{2- [3- (Aminocarbonyl) -pheninole] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzinole)-8-[ (2-aminocyclohexanol) amino] xanthine

(581) 1- {2- [3- (methylaminocarbonyl) -fuel] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- [ (2-aminocyclohexanol) amino] xanthin

 (582) 1- {2- [3- (Dimethylaminocarboel) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [ (2-aminohexylhexamino) amino] kisantin

(583) 1- {2- [3- (methylsulfonyl) -pheninole] -2-oxo-ethyl} -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[(2 -Aminoxyhexyl) amino] xanthi N

 (584) 1- {2- [3- (Methylsulfiel) -phenyl]-2-oxo-ethyl}-3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminocyclohexyl) amino] xanthine

 (58 5) 1- {2- [3- (methylsulfonyl) -phenyl] -2-oxo-ethyl} -3-methinole-7- (2-methyl-5_fluoromethylbenzyl) -8- [ (2-aminoaminohexyl) amino] xanthine

(586) 1- [2- (3,5-dimethyl-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-phenylene-benzyl)-8-[( 2-aminohexyl) amino] xanthine

 (58 7) 1- [2_ (3-fluoro-5-methyl-phenyl) -2-oxo-ethyl] -3-methyl _7_ (2-methyl-5-fluorobenzyl)-8-[(2-aminoaminocyclyl Hexyl) amino] xanthin

(5 88) 1- [2- (Pyridin-3-yl) -2_oxo-ethyl] -3-Methyl-7_ (2-Methyl-5-fluorobenzyl) -8 _ [(2-Aminoxyhexyl ) Amino] xanthine

 (5 8 9) 1- [2- (furan-2-inole) -2-oxo-ethyl ']-3-methyl-7- (2-methyl-5-funenolate)-8-[( 2-aminocyclohexyl) amino] xanthine

 (5 90) 1— [2- (thiophen-2-yl) -2-oxo-ethynole] -3-methyl-7— (2-methinole-5-fluorobenzyl) -8-[(2-aminosic Xyl) amino] xanthine

 (5 9 1) 1- [2- (thiazol-2-yl) _2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Xinole) amino] xanthine

 (5 92) 1_ [2- (thiazol-5-yl) _2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclylhexyl) Amino] xanthine

 (5 9 3) 1- [2- (thiazol-4-yl) -2-oxo-ethyl] _3_methyl _7_ (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexyl) Amino] xanthine

 (5 94) 1- (2-Fen-2-yl-hydroxyimino-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] Xanthine

 (5 95) 1- (2-Phenyl-2-methoxyimino-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (5 96) 1- (2-oxo-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexyl) amino] xanthine

(5 9 7) 1- (2-oxo-butyl) -3_methyl-7- (2-methyl-5-fluorobenzyl) -8-[( 2-aminocycline hexinole) amino] xanthin

 (598) 1- (3-Methyl-2-oxo-butyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (599) 1- (2-Cyclopropyl-2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexanol) amino] xanthine

 (600) 1- (2-Cyclohexyl-2-oxo-ethynole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (601) 1- (3-Dimethylamino-2,3-dioxo-propyl) -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2-aminoaminohexyl) amino] xanthine

 (602) 1- [3- (Piperidin-1-yl) -2,3-dioxo-propyl] -3-methyl-7- (2-methinole-5_fluorobenzyl)-8-[(2 -Aminoxy mouth hexyl) amino] xanthine

 (603) 1- (2-Phenyl-2-hydroxy-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzenole) -8-[(2-aminohexylhexyl) amino] Xanthine

 (604) 1- (2-Phenyl-2-hydroxy-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexyl) amino] xanthine

 (605) 1- (2-Feninole_2-methoxy-ethyl) _3-methinole-7- (2-methyl-5-fluorobenzinole)-8-[(2-aminocycline hexinole) amino] xanthine

 (606) 1-[(quinazoline-4-yl) methyl] -3_methyl-7_ (2-methinole-5-fluorobenzene / le) -8-[(2-aminocyclohexynole) amino] xanthine

 (607) 1-[(5-Methyl-isoxazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexinole ) Amino] xanthine

 (608) 1-[(oxazono-2-ene) methyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexyl) amino] Xanthine

 (609) 1-[(1H-Indazole-3-isle) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (610) 1-[(5-Fluoro mouth-benzo [d] isothiazole-3-inole) methyl] -3-methyl-7- (2-methinole-5-fluorobenzyl)-8-[(2-aminocide Hexinole) Rino] xanthine

(61 1) 1-[(5-Fluoro-benzo [d] isoxazole-3-inole) methyl] -3-methinole-7- (2-methyl-5-fluoromethyl) -8-[(2-aminocyclyl Mouthhexyl) amino] xanthin (612) 1-[(5-Methyl-benzo [d] isoxazol-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminocyclyl Hexyl) amino] xanthin

(613) 1-[(5-Methyl-benzo [d] isothiazonole-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclyl Methylhexyl) amino] xanthine (614) 1- (2-Cyclohexyl-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclylhexyl) Amino] xanthine

 (615) 1- [2- (2-Difluoromethoxy-phenyl) -ethynole] -3-methynole-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexoxyhexamino) amino] xanthine

 (616) 1- [2- (2-Difluoromethoxy-phenyl)-2-oxo-ethyl] -3- 3-methyl-7_ (2-methyl-5-fluorobenzyl) -8-[(2-amino- Xinole) amino] xanthin (617) 1- [2- (2-Trifluoromethoxy-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [ (2-aminocyclylhexyl) amino] xanthine

 (618) 1- [2- (Indane-4-inole) _2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocycloto Xyl) amino] xanthine

 (619) 1- [2- (Benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminoaminohexyl) amino] xanthine

(620) 1- [2- (2,2-Difluo-benzo- [1,3] dioxol-4-yl) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5 _Fluoro mouth benzyl)-8-[(2-aminohexyl) hexamino] xanthine

 (621) 1- [2- (Naphth-1-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzene)-8- [(2- Aminocycline hexinole) amino] xanthin

 (622) 1- [2- (2-Isopropyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Hexyl) amino] xanthine

 (623) 1- [2- (2-Cyclopropyl-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2- Aminocycline hexinole) amino] xanthin

(624) 1- [2- (2-Cyclopentyl-phenyl) -2-oxo-ethyl]-3-methyl-7- (2-methyl-5-fluorobenzinole)-8-[(2-aminoaminocyclyl Hexyl) amino] xanthin

(625) 1_ [2- (2-phenynofuryl) —2-oxo-ethyl] -1-methyl-7— (2-methyl— 5-Fluorobenzyl) -8-[(2_aminocyclylhexyl) amino] xanthine

 (626) 1- [2- (2-Cyclopentylmethoxy-phenyl) -2-oxo-ethyl] -3- 3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [ (2-aminocyclylhexyl) amino] xanthin

 (6 27) 1- (3-phenyl-2-oxo-propynole) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-[(2-aminocyclohexynole) amino] Xanthine

 (628) 1- (3-phenyl-3-oxo-propyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminohexyl) amino] Xanthine

 (6 29) 1- [2- (2-Methylamino-phenyl) -2-oxo-ethyl] -3-Methynole-7_ (2-Methyl-5-fluorobenzyl)-8-[(2-aminoamino Hexinole) amino] xanthin

 (6 30) 1- {2- [2- (N-cyanomethyl-N-methyl-amino) -phenyl] -2-oxo-ethyl} -3--3-methynole-7- (2-methyl-5-funoleo Mouth benzinole) -8-[(2-aminocyclylhexyl) amino] xanthine

 (63 1) 1- [2- (2-Cyanomethylamino-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 -[(2-aminohexylhexyl) amino] xanthine

(6 3 2) 1_ (2- {2-[(Methoxycarbonyl) methylamino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-methynole-5-fluorobenzyl ) -8- [(2-aminohexanol) amino] xanthine

 (63 3) 1- [2- (2-Methylsulfonylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8- [ (2-aminocyclylhexyl) amino] xanthin

 (634) 1- [2- (3-Methylamino-pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclyl Hexyl) amino] xanthin

 (63 5) 1- {2- [3- (N-cyanomethyl-N-methyl-amino) -phenyl] -2-oxo-ethyl} -3-methynole-7- (2-methyl- 5-Fluorobenzyl) -8 _ [(2-aminocyclylhexyl) amino] xanthine

(636) 1- (2- {3-[(dimethylamino) sulfonylamino] -phenyl} -2-oxo-ethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl)- 8-[(2-aminohexanol) amino] xanthine (6 3 7) 1- (2- {3-[(morpholin-4-yl) sulfonylamino] -pheninole) -2-oxo-ethyl) -3-methyl-7- (2-methyl- 5-Fluorobenzyl) -8-[(2-aminohexanol) amino] xanthine ''

 (638) 1- [2_ (3-Aminosulfo-lamino-phenyl) _2_oxo-ethyl] -3-Methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol ) Amino] xanthin

 (63 9) 1- [2- (3-Ethylsulfonylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) _8- [ (2-aminocyclylhexyl) amino] xanthin

 (640) 1_ [2- (3-isopropylsulfonylamino-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminocyclyl Mouth hexinole) amino] Xanthine

 (64 1) 1- {2- [3- (2-oxo-imidazoline-1-yl) -phenyl] -2-oxo-ethyl} -3-methinole 7- (2-methinole-5-fluoro Robenzinole) -8- [(2-aminosuccinic hexinole) amino] xanthine

 (642) 1- {2- [3- (3-Methyl-2-oxo-imidazolidin-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2- Methyl-5_fluoro mouth benzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (643) 1- {2- [3- (3-Methyl-2,5-dioxo-imidazolidine-1_yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2- Methyl-5-fluorobenzyl) -8-[(2-aminoaminohexinole) amino] xanthine

 (644) 1- {2- [3- (3-Methyl-2,4-dioxo-imidazolidine-1-yl) -phenyl] -2-oxo-ethyl} -3-methyl-7- (2 -Methyl-5-fluoro benzyl) -8-[(2-aminoaminohexyl) amino] xanthine

 (645) 1-[(1-Methyl-2-oxo-1,2-dihydro-quinoline-4-inole) methinole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[( 2-aminoaminohexyl) amino] xanthine

(646) 1-[(2-oxo-1,2-dihydro-quinazoline-4-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocinnacle Hexinole) amino] xanthin (647) 1-[(1-Methyl-2-oxo-1,2-dihydro-quinazoline-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)- 8-[(2-aminohexyl) amino] xanthin

 (648) 1-[(2-Cyano-naphthalene-1-ynole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] Xanthine

 (649) 1-[(6-cyano-naphthalene-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino ] Xanthine

 (650) 1-[(5-Cyano-naphthalene-1-ynole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclohexyl) amino ] Xanthine

 (65 1) 1-[(8-Methyl-isoquinoline-1-inole) methyl] -3-methyl-7_ (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine

 (65 2) 1-[(5-cyano-isoquinoline-1-inole) methinole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexamino) amino] Xanthine

 (65 3) 1- [(5-Aminocarbonyl-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl)-8- [(2-aminocyclyl Mouth hexinole) amino] xanthine

(654) 1-[(5-Aminosulfonyl-isoquinoline-1-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) Amino] xanthine

(6 5 5) 1-[(5-Methylsulfenoeno-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2-aminocyclyl Xyl) amino] xanthine (6 5 6) 1_ [(5-methylsulfo-lamino-isoquinoline_1 yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminocyclyl Mouth hexinole) amino] xanthine

 (65 7) 1-[(5-Methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminocyclylhexyl) Amino] xanthine

 (6 5 8) 1-[(6-Methoxy-isoquinolin-1-yl) methyl] -3-methyl-7- (2-methyl_5-fluorobenzyl) -8-[(2-aminocyclo Xyl) amino] xanthine

(6 5 9) 1_ [(7-methylsulfonylamino-isoquinoline-1-inole) methyl] -3-methinole-7- (2-methyl-5-fluorobenzyl)-8-[(2-aminohexyl hexyl ) Amino] xanthine (660) 1-[(7-cyano-isoquinoline-1-yl) methinole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] Xanthine

 (661) 1-[(7-Aminocarbyl-isoquinolin-1-yl) methyl] _3-methyl-7- (2-methyl_5-5-fluorobenzinole) -8-[(2-aminohexylhexyl) Amino] xanthine (662) 1- [2- (2-phenyloxy-phenyl) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-Aminocyclohexynole) amino] xanthine

 (663) 1_ [2_ (3 _ {[(morpholine-4-yl) canoleboninole] methoxy} -pheninole) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5- Fluorobenzyl) -8- [(2-aminocyclohexyl) amino] xanthine

 (664) 1- [2_ (3_potoxymethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminohexylhexyl) ) Amino] xanthine

(665) 1- [2- (3-Methylsulfanylmethoxy-pheninole) -2-oxo-ethynole] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2- Amino-six hexinole) amino] kisantin

 (666) 1- [2- (3-Methylsulfinylmethoxy-phenyl) -2-oxo-ethyl] -3--3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8- [( 2-aminoaminohexyl) amino] kisantin

 (667) 1- [2- (3-Methylsulfonylmethoxy-phenyl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminocyclyl Hexyl) amino] xanthin

 (668) 1_ [2- (2-oxo-2,3-dihydro-benzoxazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluoro Mouth Benzinole) -8-[(2-aminohexanol) amino] xanthine

 (669) 1- [2- (2-Oxo-2,3-dihydro-1H-benzoimidazole-4-yl) -2-oxo-ethyl] -3-methyl-7- (2- Methyl-5-fluoro mouth benzinole)-8-[(2-aminocyclohexyl) amino] xanthine

(670) 1_ [2- (1-Methyl-2-oxo-2,3-dihydro-1H-benzoimidazonole-4-yl) -2-oxo-ethyl] -3-methyl-7- ( 2-Methyl-5-fluorobenzyl)-8-[(2-aminohexanol) amino] xanthine (67 1) 1- [2- (1,3-Dimethyl-2-oxo-2,3-dihydro-1H-benzimidazole-4-inole) -2-oxo-ethyl] -3-methinole-7- (2-Methynole-5_funoleo benzyl)-8-[(2-Aminocyclohexynole) amino] xanthine

 (672) 1- [2_ (1H-benzimidazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-benzyl at the phenolic)-8- [ (2-aminosuccinic hexinole) amino] xanthine

(673) 1- [2- (2-Methyl-1H-benzimidazol-4-yl) _2_oxo-ethyl] -3- 3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminoaminohexyl) amino] kisantin

 (674) 1- [2- (Benzoxazol-4-yl) _2_oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocink Mouth hexinole) amino] xanthine

 (6 75) 1- [2- (2-Methyl-benzoxazol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8 -[(2-aminoaminohexyl) amino] xanthine

 (676) 1- [2- (3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine-5-inole-2-oxo-ethynole] -3-methyl-7- ( 2-methyl-5-fluorobenzinole) -8-[(2-Aminocyclohexynole) amino] xanthine

 (6 77) 1- [2- (Benzo [1,3] dioxol-4-yl) -2-oxo-ethyl] -3-methyl-7- (2-methinole-5-fluorobenzinole) -8-[(2-aminocyclylhexyl) amino] xanthine

(6 78) 1- (1-Methoxycarbonyl-1 -pheninole-methyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (6 79) 1- (1-Felpoxy-1-phenyl-methyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] Xanthine

 (680) 1- (1-Aminocarbonyl-1-phenyl-methyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (68 1) 1- (1-Methoxycarbonyl-2-phenyl-ethynole) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (68 2) 1- (1-Carbonyl-2-phenyl-2-ethyl) -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

(68 3) 1- (1-aminocarbonyl-2-phenyl-ethyl) -3-methyl-7- (2-methyl-5- Fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

(684) 1-[(Benzofuran-2-inole) methyl] -3-methyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

 (685) 1-[(2,3-dihydro-benzofuran-2-yl) methyl] -3-methyl-7- (2-methyl-5-funolenobenzinole) -8-[(2-aminocycline Hexi / re) amino] xanthine

 (686) 1 [2— (2-Amino-3-cyano-pheninole) -2 -oxoxethyl] -3-Methyl-7-(2-Methyl_5 -Fluorobenzyl)-8-[(2 Hexinole) amino] xanthin

(687) 1 [2- (2-Amino-3-fluo-mouth-fuel) -2-oxo-ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2- Aminocyclohexinole) amino] xanthin (688) 1_ (1-methyl-2-phenyl-2-oxo-ethyl) -3-methinole-7_ (2-methinole-5-fluorobenzyl) -8-[( 2-aminocyclohexyl) amino] xanthin

 (689) 1- [2-oxo-2,3- (3-oxo-3,4-dihydro-2H-benzo [1,4] oxazine-8-inole) -ethynole] -3-methyl-7- (2- Methyl-5-fluorobenzyl)-8-[(2-aminoxinolexamino) amino] xanthine

 (690) 1- [2-oxo-2- (4-methinole-3-oxo-3,4-dihydro-2H-benzo [1,4] oxosin-8-yl) -ethyl] -3 -Methinole-7- (2-Methinole-5-fluorobenzyl) -8-[(2-aminohexyl) amino] xanthine

 (691) 1-[(2-oxo-2H-couphene-4-inole) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2- Aminocycline hexinole) amino] xanthin

 (692) 1-[(1-oxo-1,2-dihydro-isoquinolin-4-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminoaminocyclyl Mouth hexinole) amino] xanthine

(693) 1-[(2-Methyl-1-oxo-1,2-dihydro-isoquinoline-4-inole) methyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8-[( 2-Aminoxyhexyl) amino] kisantin

 (694) 1- [(4-Oxo-3,4-dihydro-phthalazine-1-ynole) methyl] -3-methyl-7- (2-monomethyl-5-fluorobenzyl) -8-[(2- Aminocyclohexyl) amino] xanthine

(695) 1-[(3-Methyl-4-oxo-3,4-dihydro-phthalazin-1-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- [(2-aminocyclylhexyl) amino] xanthin (696) 1-[([1,5] naphthyridin-4-yl) methyl] -3-methyl-7- (2-methyl-5-phenolylbenzyl) -8-[(2-aminocyclyl hexinole) Amino] xanthine

 (697) 1-[([1,7] naphthyridin-8-yl) methyl] -3-methyl-7_ (2-methyl-5_fluorobenzyl)-8-[(2-aminocyclohexanol) amino ] Xanthine

 (698) 1-[(quinolin-2-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] xanthine

 (699) 1-[(Isoquinolin-3-yl) methyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] xanthine

 (700) 1_ {2-oxo-2- [3- (2-oxo-tetrahydro-pyrimidine-1-yl) -phenyl] -ethyl} -3-methyl-7- (2-methyl-5- Fluorobenzyl) -8-[(2-aminohexyl) amino] xanthine

 (701) 1- {2-oxo-2- [3- (3-methyl-2-oxo-tetrahydro-pyrimidine-1-yl) -phenyl] -ethyl} -3-methyl-7- (2 -Methyl-5-fluorobenzyl) _8 _ [(2-aminohexyl) amino] xanthine

 (702) 1- (2-Phenyl-2-oxoethyl) -3-methyl-7- (2-c-mouth-5-fluorobendinole)-8-[(2-aminocyclohexyl) amino] xanthine

 (703) 1- (2-Phenyl-2-oxoethynole) -3-methyl-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (704) 1 [(Isoquino-Vin-1-yl) methyl] -3-methyl-7- (2-cyclo-5-fluorobenzyl) -8-[(2-aminoaminohexyl ) Amino] xanthine

 (705) g [(isoquinoline-1-inole) methyl] -3-methyl-7- (2-bromo-5-fluorobenzinole) -8-[(2-aminocyclohexyl) amino] xanthine

 (706) 1- [2- (Pyridin-2-yl) ethyl] -3-methyl-7- (2-cyclo-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino ] Xanthine

 (707) 1- [2- (Pyridin-2-yl) ethyl] _3_methyl-7- (2-bromo-5_fluorobenzyl) -8-[(2-aminocyclylhexyl) amino] xanthine

 (708) 1- [2- (2-Naphthinole) ethyl] -3-methyl-7- (2-c-mouth-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine

(709) 1_ [2_ (2-naphthyl) ethyl] _3-methyl-7- (2-promo-5_fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (710) 1- [2- (2-Methoxyethoxy) -2-oxoethyl] -3-methyl-7- (2-co- mouth-5-fluoro-benzyl) -8-[(2-aminoschico mouth Hexyl) amino] xanthine

 (71 1) 1-[2- (2-Methoxyphenyl) -2-oxoethyl] -3-methyl-7- (2-bromo-5-fluorobenzyl) _8-[(2-aminocyclohexyl) amino ] Xanthine

 (712) 1- [2- (3-Methoxyphenyl) -2-oxo-ethyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocyclylhexyl) Amino] xanthine

 (713) 1- [2- (3-Methoxypheninole) -2-oxoxenoline] -3-Methinole-7_ (2-promo-5-fluorobenzyl) _8-[(2-aminocyclohexyl) amino] xanthine

 (714) 1- [2- (2-Chlorophenyl) _2-oxoethyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8 _ [(2-aminocyclohexyl) amino] Xanthine

 (715) 1- [2- (2-chlorophenyl) -2-oxoethyl] -3-methyl-7- (2-promo-5-fluorobenzyl) -8-[(2-aminocyclohexanol ) Amino] xanthine

 (716) 1— [2- (3-chloro mouth) -2_oxoethyl] -3-Methyl _7_ (2-black mouth-5-fluoro benzyl) -8-[(2-amino mouth Hexyl) amino] xanthine

 (717) 1_ [2- (3-Chloroquinone) -2-oxochineno] -3-methinole-7- (2-promo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) Amino] xanthine

 (718) 1- (2-phenylethyl) -3-methinole-7- (2-chloro-5-fluorobenzinole) -1- 8-[(2-aminocyclylhexinole) amino] xanthine

 (719) 1- (2-Fenrhetinole)-3-Methinole-7- (2-Buguchimo-5-Funolebenbenole) -8-[(2-Aminocyclohexyl) amino] xanthine

 (720) 3-Methyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

 (721) 3-Methyl-7- (2-co-mouth-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine

 (722) 3-Methyl-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine

(723) 1- [2- (phenyl) ethyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8-1-[(2-aminocyclohexyl) amino] xanthine, (724) 1-[(pyridine-2-yl) methyl] -3-methyl-7- (2_chloro-5-fluorobenzyl) -8-[(2-aminocyclohexyl) mino] xanthine,

 (725) 1- [2- (2-Fluorophenylinole) ethyl] -1-3-methinole-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine ,

 (726) 1- [2 -— (2-cloth feninole) etinole] -3-methinole—7— (2-ku-guchi-5-funoleo benzyl) -8-[(2-Aminoc Xinole) amino] xanthin,

 (727) 1- [2- (2-Bromophene-noreth) ethyl] -3-methyl-7- (2-co- mouth-5-fluoro-benzyl) -8-[(2-aminocyclohexyl) Amino] xanthine,

 (728) 1- [2- (2-Cyanophenyl) ethynole] -3-Methinole-7- (2-c-mouth-5-funoleo-benzyl)-8-[(2-aminocyclohexyl) amino Xanthin,

 (729) 1- [2_ (2-methoxyphenyl) ethyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine,

 (730) 1- [2- (2-methylfe-noreth) ethyl] -3-methyl-7- (2-c-mouth-5-fluoro-benzyl) -8-[(2-amino-hexanol) Amino] xanthine,

 (731) 1- [2- (3-Fluorophenyl) ethyl] -3-methyl-7- (2-coguchi-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine,

 (732) 1_ [2- (3-Mouthphenyl) ethyl] -3-methyl-7- (2-Mouth-5-fluorobenzyl)-8-[(2-Aminochenylhexyl) Amino] xanthine,

 (733) 1- [2- (3-Promofeninole) ethyl] -3-methinole-7- (2-c-mouth-5-fluoro-benzinole) -8-[(2-aminohexyl hexyl) Rino] xanthine,

 (734) 1- [2- (3-Cyanophenyl) ethyl] -3-methyl-7- (2-chloro-5-fluoromethylbenzyl) -8-[(2-aminocyclohexynole) amino] xanthine,

 (735) 1_ [2_ (3-methoxyphenole) ethinole] _3-methinole-7- (2-chloro-5-funoleo benzyl) -8-[(2-aminocyclohexynole) amino] xanthine,

 (736) 1- [2- (3-Methylphenyl) ethynole] -3-Methynole-7- (2-chloro-5-funoleobenzyl) -8-[(2-Aminocyclohexynole) amino] xanthine ,

 (737) 1- [2- (Phenyl) -2-oxoethyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] Xanthine,

(738) 1- [2- (2-Fluorophieel) -2-oxoxethyl] -3-methyl-7- (2-chloro- mouth-5- Fluorinated benzyl) -8-[(2-aminocyclohexyl) amino] xanthine,

 (739) 1- [2- (2-Bromophenyl) -2-oxoethyl] -3-methyl-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminohexyl) amino] Xanthine,

 (740) 1- [2- (2-Cyanophenyl) -2-oxohexyl] -3-methyl-7- (2-cyclo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino Xanthin,

 (741) 1- [2- (2-Methylphenyl) -2-oxo-ethyl] -3-methyl-7_ (2-chloro-5-fluorobenzyl) -8-[(2-aminohexylhexamino) amino Xanthin,

 (742) 1- [2- (3-fluorophenyl) -2-oxoethyl] -3-methyl-7- (2-co-5-fluorobenzyl) -8-[(2-aminocyclohexyl / Re) Amino] xanthine,

 (743) 1- [2_ (3-Bromophenyl) -2-oxoethyl] -3-methyl-7- (2-chloro-5-phenolobenzyl)-8-[(2-aminocyclohexyl) amino Xanthin,

 (744) 1_ [2- (3-Cyanophenyl) -2-oxohexyl] -3-methyl-7- (2-co-mouth-5-fluorobenzyl) -8-[(2-aminocyclohexanol) Amino] xanthine,

 (745) 1- [2- (3-Methinolepheninole) -2-oxoetinole] -3-Methinole-7- (2-Mouth mouth-5-Fluoro mouth benzyl) -8- [(2-aminocyclyl Hexyl) amino] xanthin,

 (746) 1- [2- (phenyl) ethyl] -3-methyl-7- (2-bromo-5-fluorobenzinole) -8-[(2-aminocyclohexynole) amino] xanthine,

 (747) 1-[(pyridin-2-yl) methyl] _3-methyl-7- (2-bromo-5-fluorobenzinole) -8 _ [(2-aminocyclohexynole) amino] xanthine,

 (748) 1- [2- (2-fluorophenyl) ethyl] -3-methyl-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine ,

 (749) 1— [2 -— (2-chlorophenol) ethyl] -1-methyl-7_ (2_bromo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino Xanthin,

 (750) 1- [2- (2-bromophenyl) ethyl] -3-methyl-7- (2-promo-5-fluorobenzyl) -8-[(2-aminocyclohexanol) amino] xanthine,

 (751) 1- [2- (2-Cyanophenyl) ethyl] -3-methyl-7- (2-butamo-5-fluorobenzyl) -8-[(2-aminocyclohexamino) amino] Xanthine,

(752) 1- [2- (2-methoxyphenyl) ethyl] -3-methyl-7- (2-promo-5_fluoro Benzyl) -8_ [(2-aminocyclohexanol) amino] xanthine,

 (75 3) 1- [2- (2-methylpheninole) ethyl] -3-methyl-7- (2-buta-5-fluorobenzyl) -8-[(to the 2-aminocyclyl mouth Xinole) amino] xanthin,

 (754) 1- [2- (3-fluorophenyl) ethyl] -3-methinole-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine,

 (75 5) 1— [2- (3-chloropheninole) ethynole] -3-methyl-7- (2-butane-5-fluorobenzyl) -8- [ Xyl) amino] xanthine,

 (756) 1- [2- (3-Bromophenyl) ethyl] -1-3-methinole 7- (2-butaquinone-5-fluorobenzil) -8-[(2-aminohexylhexyl / re) Amino] xanthine,

 (75 7) 1_ [2- (3-Cyanophenyl) ethyl] -3-methyl-7- (2-bromo-5-fluorobenzyl)-8-[(2-aminocyclohexyl) amino Xanthin,

 (758) 1- [2_ (3-methoxyphenole) ethyl] -3-methyl-7- (2-promo-5-fluorobenzyl) -8-[(2-aminocyclohexynole) amino] xanthine,

 (75 9) 1- [2- (3-methylpheninole) ethyl] -3-methyl-7- (2-buta-5-fluorobenzyl) -8-[(2-aminocyclohexinole Amino] xanthin,

 (760) 1-[2- (Feninole) -2 -oxoethyl]-3 -Methinole-7- (2-Bumo-5-Fluoro benzyl) -8- [(2-Aminoc hexinole Amino] xanthin,

 (76 1) 1- [2- (2-fluoroethyl) -2-oxoethyl] -3-methyl-7- (2-butamo-5-fluorobenzyl) -8-[(2-aminoamino Hexinole) amino] xanthin,

 (76 2) 1- [2- (2-bromophenyl) -2-oxoethyl] -3-methyl-7- (2-butamo-5-fluorobenzyl) -8-[(2-aminoamino Hexinole) amino] xanthin,

 (76 3) 1- [2- (2-Cyanophenole) -2-oxochichinore] -3--Methinole-7- (2-butamo-5-fluorobenzyl)-8-[(2-aminocyclohexene) Amino] xanthine,

 (764) 1- [2- (2-methylphenyl) -2-oxoethyl] -3-methyl-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclylhexamino) amino Xanthin,

 (765) 1- [2- (3-Fluorophenyl) -2-oxoethyl] -3-methinole-7_ (2-bromo-5-fluorobenzyl)-8-[(2-aminocyclohexanol) amino] xanthine ,

(766) 1- [2- (3-Bromophenyl) -2-oxoethyl] -3-methinole-7- (2-butamo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino Xanthin, (767) 1- [2- (3-cyanophenol) -2-oxoethyl] _3-methyl_7_ (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine,

 (768) 1- [2- (3-Methylphenyl) -2-oxoethyl] -3-methyl-7- (2-bromo-5-fluorobenzyl) -8-[(2-aminocyclohexyl) amino] xanthine ,

 (769) 1,3-Dimethyl-7- (2-methyl-5-fluorobenzyl) _8-[(2-aminocycloheptyl) amino] xanthine

 (770) 1,3_dimethyl-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocycloheptinole) amino] xanthine

 (771) 1,3-dimethyl-7_ (2-bromo-5-fluorobenzyl) -8-[(2-aminocycloheptyl) amino] xanthine

 (772) 1,3-dimethyl-7- (2-methyl-5-fluorobenzyl) -8-[(2-aminocyclopentinole) amino] xanthine

 (773) 1,3-dimethyl-7- (2-chloro-5-fluorobenzyl) -8-[(2-aminocyclopentinole) amino] xanthine

(774) 1,3-Dimethyl-7_ (2-promo-5-fluorobenzyl) -8-[(2-aminocyclopentinole) amino] xanthine

番号 γ

Compound _γ 1 Compound _γ 1

Number γ

 Esmine

CT0 / C00Zdf / X3d contract OOZ OAV Four

Compound _v1 Compound Object number γ γ Compound Υ '

上記 No. 352〜No.817の化合物において、 ジァミノ基が下記式 （D) ま たは式 （E) で表される絶対配置を有するシクロアルカンジァミン化合物が好まし い。

In the compounds of Nos. 352 to 817, a cycloalkanediamine compound having a diamino group having an absolute configuration represented by the following formula (D) or (E) is preferable.

— H NH ₂

) q () (E)

R

(Wherein, q and R ⁵ are as defined above.)

 In the above compounds of Nos. 352 to 817, a cycloalkylamine compound having a diamino group having an absolute configuration represented by the following formula (D) is more preferable.

NH ₂ ) _q (D)

(Wherein, q and R ⁵ are as defined above.)

 In the following description, when a bond is represented by a solid line and a broken line wedge as in formulas (D) and (E), the absolute configuration of the amino group is represented, and the bond is thickened as in formula (F). When represented by a line, the relative configuration of an amino group (for example, the formula (F) represents (Sat) -cis isomer) is assumed.

(In the formula, q and R ⁵ have the same meanings as described above.) Further, as a preferred example of the xanthine compound of the present invention, the following 3_aminobiperidine compound can be exemplified.

o. R ¹ R ² R ³

818 CH ₃ CH ₃ CHF ₂ 0

819 CH ₃ CH ₃ CF ₃ CF ₂ 0

820 CH ₃ CH ₃ CF3O

821 CH ₃ CH ₃ C ₂ H ₅

822 CH ₃ CH ₃ CN

823 CH ₃ CH ₃ CH3 (CH2) 2

824 CH ₃ CH ₃ (CH ₃ ) ₂ CH

827 CH ₃ CH ₃ CH ₃ (CH ₂ ) ₂₀

828 CH ₃ CH ₃ (CH ₃ ) ₂ CHO

829 CH ₃ CH ₃ (^ CH ₂ 0

830 CH ₃ CH ₃ <^^ CH ₂ 0

831 CH ₃ CH ₃ CH ₃ S (0) ₂

832 CH ₃ CH ₃ CH ₃ S (O)

833 CH ₃ CH ₃ CH ₃ S

834 CH ₃ CH ₃ CO ₂ H

835 CH ₃ CH ₃ CONH ₂

836 CH ₃ CH ₃ CONHCH3

837 CH ₃ CH ₃ CON (CH ₃ ) ₂

838 CH ₃ CH ₃ I

839 CH ₃ CH ₃ F

840 CH ₃ CH ₃ NH ₂

841 CH ₃ CH ₃ NHCH ₃

842 CH ₃ CH ₃ N (CH ₃ ) ₂

843 CH ₃ CH ₃ CI

844 CH ₃ CH ₃ CH3O

No. R ¹ R ² R ³

845 H CH ₃ CHF ₂ 0

846 H CH ₃ CF ₃ CF ₂ 0

847 H CH ₃ CF3O

848 H CH ₃ C2H5

849 H CH ₃ CN

850 H CH ₃ CH3 (CH2) 2

851 H CH ₃ (CH ₃ ) ₂ CH

852 H CH ₃ CH3O

853 H CH ₃ CI

854 HC ₂ H ₅ CHF ₂ 0

855 H C2H5 CF3CF2O

856 H C2H5 CF3O

857 H C2H5 C2H5

858 H C2H5 CN

859 H C2H5 CH ₃ (CH ₂ ) ₂

860 H C2H5 (CH ₃ ) ₂ CH

861 HC ₂ H ₅ CH3O

862 HC ₂ H ₅ CI

863 CH ₃ CH ₃ CH ₃ C (0)

864 CH ₃ CH ₃ C ₂ H ₅ C (O)

No. R ¹ R ² R ³

865 CH ₃ CH ₃ CH ₂ = CH

866 CH ₃ CH ₃ (E) -CH ₃ CH = CH

867 CH ₃ CH ₃ (Z) -CH ₃ CH = CH

868 CH ₃ CH ₃ CH ₂ = CHCH ₂

869 CH ₃ CH ₃ HOCH ₂ CH ₂

870 CH ₃ CH ₃ NCCH ₂ CH ₂

871 CH ₃ CH ₃ HOC (0) CH ₂

872 CH ₃ CH ₃ H ₂ NC (0) CH2

873 CH ₃ CH ₃ CH ₃ C≡C

Of the compounds of No. 818 to No. 873 described above, those in which the 3-position of 3-aminobiperidine is in the R-configuration are more preferred.

93α '' a HO HO 6!

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£ l0 / £ 00idT / I3d 6. £ 8l70 / l700Z: OAV D1 to D32 mean the following substituents.

CT0/C00Zdf/X3d 請 OOZ OAV D 1〜D 3 1において、 3 -アミノビペリジンのァミノ基が下記式 （C ) で表され る立体配置と同一の立体配置を有する各置換基が、 より好ましい。 すなわち具体的 には、 D 1〜D 2 9においては 3位が R—配置、 D 3 0および D 3 1においては 3位 が S—配置である各置換基が、 より好ましい。

以下に、 本発明における式 （I) で表される化合物の製造法について、 例を挙げて 説明するが、 本発明はもとよりこれに限定されるものではない。 なお、 本明細書に おいて、 記載の簡略化のために次の略語を使用することもある。

CT0 / C00Zdf / X3d contract OOZ OAV In D 1 to D 31, each substituent in which the amino group of 3-aminobiperidine has the same configuration as the configuration represented by the following formula (C) is more preferable. That is, specifically, each substituent in which the 3-position in D1 to D29 has an R-configuration and the 3-position in D30 and D31 has an S-configuration is more preferable.

Hereinafter, the method for producing the compound represented by the formula (I) in the present invention will be described with reference to examples, but the present invention is not limited thereto. In this specification, the following abbreviations may be used for the sake of simplicity.

 B o c: tert-butoxy canoleboninole group

 The compound represented by the formula (I) can be synthesized from known compounds by combining known synthesis methods. For example, it can be synthesized by the following method. Manufacturing method 1

Among the compounds represented by the formula (I), the compound represented by the formula (8) or a salt thereof is produced by, for example, a method shown below.

9

9

[Wherein, I ¹ , R ² , R ³ , R ⁴ and n are as defined above. X ¹ and X ² represent an iodine atom, a bromine atom, a chlorine atom, methanesulfonyloxy, trifluoromethanesulfonyloxy, p-toluenesulfonyloxy, or the like. ]

1) Process 1

 Compound (2) can be produced by reacting compound (1) with bromine in an inert solvent in the presence or absence of an additive (J. Heterocycl. Chem. 37, 1033 (2000) J. Chem. Soc., Perkin Trans. 113, 1833 (1999), J. Med. Chem. 38, 3838 (1995), etc.). Examples of the additive include sodium acetate and the like, and the amount of the additive is generally selected from the range of 1 to 5 equivalents relative to compound (1). The amount of bromine to be used is generally selected from the range of 1 to 3 equivalents relative to compound (1). Examples of the inert solvent include water, alcohols (eg, ethanol, methanol, isopropanol), ether, 4-dioxane, etc.), organic acids (eg, acetic acid, propionic acid), and mixed solvents thereof. The reaction temperature can be selected from the range of about 20 ° C to about 50 ° C.

 2) Process 2

Compound (4) can be produced by reacting compound (2) with compound (3) in an inert solvent in the presence of a base (J. Heterocycl. Chem. 37, 1033 (2000), J. Chem. Soc., Perkin Trans. 113, 1833 (1999), J. Med. Chem. 38, 3838 (1995), etc.). The amount of compound (3) to be used is generally selected from the range of 1 equivalent to 3 equivalents relative to the compound of formula (2). Examples of the base include, for example, aluminum carbonate (carbonate, sodium carbonate, lithium hydrogencarbonate, sodium hydrogencarbonate, etc.) and aluminum hydroxide (potassium hydroxide, sodium hydroxide, etc.). Examples include potassium carbonate and the like. The amount of the base to be used is generally selected from the range of 1 to 5 equivalents relative to compound (2). Examples of inert solvents include aprotic solvents (dimethylformamide, dimethylsulfoxide, etc.), ethers (getyl ether, tetrahydrofuran, 1,4-dioxane, etc.), ketones (acetone, etc.), mixed solvents of these, etc. And preferably dimethylformamide, dimethylsulfoxide and the like. The reaction temperature can be selected from the range of about 10 ° C to about 50 ° C. 3) Process 3

 Compound (6) can be produced by reacting compound (4) with compound (5) in an inert solvent in the presence of a base. The amount of compound (5) to be used is generally selected from the range of 1 to 3 equivalents based on compound (4). Examples of the base include aluminum carbonate (lithium carbonate, sodium carbonate, hydrogen carbonate, sodium hydrogen carbonate, etc.), alkali hydroxide (hydroxide, sodium hydroxide, etc.), hydrogen hydride Power (sodium hydride, hydrogenation power, etc.), alkoxyal power (tert-butoxy power, etc.) and the like, and preferably, lithium carbonate, sodium hydride and the like. The amount of the base to be used is generally selected from the range of 1 to 5 equivalents based on compound (4). As the inert solvent, for example, aprotic solvents (dimethylformamide, dimethinoresnoleoxide, etc.), ethenore (jetizoleatenole, tetrahydrofuran, 1,4-dioxane, etc.), ketone (acetone) And the like, and a mixed solvent thereof, and more preferably, dimethylformamide and the like. The reaction temperature can be selected from the range of about 10 ° C. to about 10 ° C.

4) Process 4

ミン、 トリェチルァミン、 ピリジン、 4 - (ジメチルアミ ノ）ピリジン、 N -メチルモルホリン等が挙げられ、 好適にはジィソプロピルェチル ァミン、 トリェチルァミン等が挙げられる。 塩基の使用量としては、 化合物 （6 ) に対し通常 1〜5当量の範囲から選択される。 不活性溶媒としては、 アルコール (ェ タノール、 メタノール、 イソプロパノール等）、 エーテル（1， 4 -ジォキサン等）、 これらの混合溶媒等が挙げられる。 反応温度としては、 約 5 0 °C〜約 1 5 0 °Cの範 囲から選択することができる。 また、 オートクレープなどの密閉反応容器で反応を 行うこともできる。 製造法 2 Compound (8) can be produced by reacting compound (6) with compound (7) in an inert solvent in the presence or absence of a base. As a base, for example

Min, triethylamine, pyridine, 4- (dimethylamino) pyridine, N-methylmorpholine and the like, preferably diisopropylpropylethylamine and triethylamine. The amount of the base to be used is generally selected from the range of 1 to 5 equivalents based on compound (6). Examples of the inert solvent include alcohols (eg, ethanol, methanol, isopropanol), ethers (eg, 1,4-dioxane), and mixed solvents thereof. The reaction temperature can be selected from the range of about 50 ° C to about 150 ° C. The reaction can also be carried out in a closed reaction vessel such as an autoclave. Manufacturing method 2

Among the compounds represented by the formula (I), the compound represented by the formula (8) or a salt thereof is produced by, for example, a method shown below.

[Wherein, RR ² , R ³ , R ⁴ and n are as defined above. ]

 1) Process 1

 Compound (10) can be produced from compound (6) by the same method as in step 4 of production method 1.

 2) Process 2

Compound (8) can be produced by optically resolving compound (10). As the optical resolution method, the compound (10) is dissolved in an inert solvent (for example, an alcohol solvent such as methanol, ethanol or 2-propanol, an ether solvent such as getyl ether, an ester solvent such as ethyl ester, etc.). A hydrocarbon-based solvent such as toluene, or acetonitrile, etc., and a mixed solvent thereof), an optically active acid (eg, a monocarboxylic acid such as mandelic acid, N-benzyloxyalanan, or lactic acid, tartaric acid, o -Dicarboxylic acid such as diisopropylidene tartaric acid or malic acid, or sulfonic acid such as camphors / lefonic acid or bromocamphorsnolephonic acid). Examples of the temperature at which the salt is formed include a range from room temperature to the boiling point of the solvent. In order to improve the optical purity, it is desirable to raise the temperature once to near the boiling point of the solvent. Before the precipitated salt is collected by filtration, the salt can be cooled if necessary to improve the yield. The amount of the optically active acid or amine used is in the range of about 0.5 equivalent to about 2.0 equivalent, preferably about 1 equivalent, relative to the substrate. The surroundings are appropriate. If necessary, the crystals are placed in an inert solvent (eg, methanol, ethanol,

Recrystallized with alcohol solvents such as 2-propanol, ether solvents such as getyl ether, ester solvents such as ethyl acetate, hydrocarbon solvents such as toluene, acetoetrile, etc. An optically active salt can also be obtained. If necessary, the obtained salt can be treated with an acid or a base in a usual manner to obtain a free compound. The compound (8) can be produced by fractionating the compound (10) using a commercially available chiral column. Manufacturing method 3

Among the compounds represented by the formula (I), the compound represented by the formula (10) or a salt thereof is produced, for example, by the method shown below.

 (Ten)

[Wherein, RR ² , R ³ , R ⁴ and n are as defined above. ]

1) Process 1

 Compound (12) can be produced from compound (6) by a method similar to that in step 4 of production method 1.

2) Process 2 Compound (10) can be produced by deprotecting the Boc group of compound (12) in an inert solvent in the presence of an acid. Examples of the acid include hydrochloric acid, sulfuric acid, trifluoroacetic acid and the like, and preferably trifluoroacetic acid and the like. The amount of the acid to be used is generally selected from the range of 1 equivalent to 5 equivalents relative to compound (12). Examples of the inert solvent include halogenated hydrocarbon solvents (dichloromethane, dichloroethane, chloroform, etc.), ethers, 4-dioxane, etc., and mixed solvents thereof. The reaction temperature can be selected from the range of about -20 ° C to about 30 ° C. Manufacturing method 4

As shown below, compound (11) can be produced from compound (13) according to the method described in, for example, J. Org. Chera. 58, 879 (1993).

Wherein R ⁴ and n are as defined above. As a specific example of the compound (7), a synthesis example of the compound (7-9) from the compound (7-1) is shown below. Compounds (7-1) to (7_9) include pharmaceutically acceptable salts.

Three

 Compound manufacturing method

s. 40, 1 19 (1992) 8, 327 (1997) 1 1, 567 (2000)

Table 14 Production methods for compounds

 6, 2830 (2000)

twenty five

oc.Jpn. 53, 2605 (1980)

 (7-8)

Starting from compound (7-8)

 J. Am. Chem. Soc. 80,2584 (1958), or Chem. Soc. PT1 499 (1972)

に記載の方法に従う。

Follow the method described in

 (7-9)

As a specific example of compound (7), a synthesis example of compound (7-18) from compound (7-10) is shown below. Compounds (7-10) to (7_18) include pharmaceutically acceptable salts. Table 15 Method for producing compound Using compound (7-6) as a starting material, the method described in, for example, J. Chem. Soc. Chem. Commun. 611 (1981) is used.

Using the compound (7-6) as a starting material, the method described in, for example, J. Chem. Soc. Chem. Commun. 611 (1981) is followed.

Starting from compound (7-8) as a starting material, for example, J. Org. Chem. 44, 3872 (1979)

 Follow the method described in

Starting from compound (7-5) as a starting material, for example, J. Org. Chem. 44, 3872 (1979)

 Follow the method described in

 Starting from compound (7-8) as a starting material

 According to the method described in HN Bull. Chem. Soc. Jpn. 64, 2857 (1991).

NH (7-14) Table 16

 Compound manufacturing method

₂ に記載の方法に従う。

Follow the method described in ₂ .

 Three

(7-17 A): Y ° = NHS (0) ₂ CH ₃

(7-17B): 丫³ = NHC (0) CH ₃

(7 -17C): Y ³ = NHC (0) C ₆ H ₅

(7-17D): Y ³ = N (CH ₃ ) C (0) CH ₃

また、 化合物 （7) は、 置換 D-オル-チンから、 公知の方法で合成することがで きる。具体的に fま Comprehensive Organic transformation , R. C. フロック著， V CH publisher Inc., 1989に記載されている方法等が挙げられる。

Compound (7) can be synthesized from substituted D-ortin by a known method. Specific examples include the method described in V. Comprehensive Organic transformation, RC Flock, VCH publisher Inc., 1989.

As a specific example of the compound (9), an example of the synthesis of the compound (9-14C) from the compound (9-1-1A) is shown below. Compound (9-1A) to compound (9-14C) include pharmaceutically acceptable salts. 00

7 Compound production method

(9-1A): Z ¹ = CH ₃

(9-1B): Z ¹ = CH ₂ CH ₃

(9-1C): Z ¹ = CH ₂ CH ₂ OH

(9-1D): Z ¹ = CH ₂ CH ₂ F

(9-1E): Z ¹ = H

J. Org. Chem. 44, 2732 (1979)

Starting from compound (9-1-2), for example,

 According to the method described in J. Org. Chem. 44, 3872 (1979).

 (9-3)

Arch. Pharm.322, 499 (1989)

(

(9-4B): Z ³ = CH ₂ CH ₃

(9-4C): Z ³ = CH ₂ CH ₂ CH ₃

As the hydrochloride of the compound (91-IE), a commercially available product can be used. Compound (9) can be synthesized from substituted DL-orditin by a known method. Specific examples include the method described in Comprehensive Organic transformation, RC Laroch, VCH publisher Inc, 1989. 0

Manufacturing method 5

Among the compounds represented by the formula (I), the compound represented by the formula (16) or a salt thereof is produced, for example, by the method shown below.

[Wherein, RR ² , R ³ , R ⁵ and q are as defined above. ]

 1) Process 1

 Compound (15) can be produced by reacting compound (6) with compound (14) in an inert solvent in the presence or absence of a base. Examples of the base include diisopropylethylamine, triethylamine, pyridine, 4- (dimethylamino) pyridine, N-methylmorpholine, and the like, and preferably, diisopropylethylamine. The amount of the base to be used is generally selected from the range of 1 to 10 equivalents based on compound (6). Examples of the inert solvent include N-methyl-2-piridone, dimethylformamide, toluene, and a mixed solvent thereof. Preferable examples include N-methyl-2-piperidone and the like. The reaction temperature can be selected from the range of about 50 ° C to about 200 ° C. The reaction can also be carried out in a closed reaction vessel such as an autoclave.

2) Process 2 Compound (16) can be produced by optically resolving compound (15). As the optical resolution method, compound (15) is dissolved in an inert solvent (for example, an alcohol solvent such as methanol, ethanol, or 2-propanol, an ether solvent such as getyl ether, an ester solvent such as ethyl acetate, toluene). , Acetonitrile and the like, and a mixed solvent thereof), an optically active acid (for example, monocarboxylic acid such as mandelic acid, N-benzyloxyalanine, or lactic acid, tartaric acid) And dicarboxylic acids such as isopropylidene tartaric acid or malic acid, or sulfonic acids such as camphorsulfonic acid or bromocamphorsulfonic acid). The temperature at which the salt is formed may be in the range from room temperature to the boiling point of the solvent. In order to improve the optical purity, it is desirable to raise the temperature once to near the boiling point of the solvent. Before the precipitated salt is collected by filtration, the salt can be cooled as necessary to improve the yield. The amount of the optically active acid or amine used is in the range of about 0.5 equivalent to about 2.0 equivalent, preferably about 1 equivalent, relative to the substrate. If necessary, crystallize the crystals in an inert solvent (for example, alcohol solvents such as methanol, ethanol, and 2-propanol; ether solvents such as getyl ether; ester solvents such as ethyl acetate; and hydrocarbon solvents such as toluene. , Acetonitrile and the like and a mixed solvent thereof) to obtain a high-purity optically active salt. If necessary, the obtained salt can be treated with an acid or base by a usual method to obtain a free form. The compound (16) can be produced by fractionating the compound (15) using a commercially available chiral column. Manufacturing method 6

Among the compounds represented by the formula (I), the compound represented by the formula (16) or a salt thereof is produced, for example, by the following method.

[Wherein, RRRR ⁵ and q are as defined above. ]

1) Process 1

 Compound (16) can be produced from compound (6) by a method similar to that of step 1 of production method 5. Compound (16) can be separated as an optically active compound, if necessary, by the same method as in Step 2 of Production Method 5. Manufacturing method 7

Among the compounds represented by the formula (I), the compound represented by the formula (19) or a salt thereof is produced, for example, by the following method.

[Wherein, RR ² , R ³ , R ⁵ and q are as defined above. ]

 1) Process 1

 Compound (19) can be produced from compound (6) by the same method as in step 1 of production method 5. Manufacturing method 8

Among the compounds represented by the formula (I), the compound represented by the formula (16) or a salt thereof is produced, for example, by the following method.

[Wherein, RR ² , R ³ , R ⁵ and q are as defined above. ]

 1) Process 1

 Compound (21) can be produced from compound (6) by a method similar to that of step 1 of production method 5.

 2) Process 2

 Compound (16) can be produced by deprotecting the Boc group of compound (21) in an inert solvent in the presence of an acid. Examples of the acid include hydrochloric acid, sulfuric acid, and trifluoroacetic acid, and more preferably, trifluoroacetic acid and the like. The amount of the acid to be used is generally selected from the range of 1 to 5 equivalents based on compound (21). Examples of the inert solvent include halogenated hydrocarbon solvents (such as dichloromethane, dichloroethane, and chloroform), ethers (such as 1,4-dioxane), and mixed solvents thereof. The reaction temperature can be selected from the range of about -20 ° C to about 30 ° C. Manufacturing method 9

Compound (20) can be produced, for example, from compound (22) whose production method is described in J. Org. Chem. 50, 4154 (1985), as shown below. 05

Process 3

 (25) (20)

Wherein R ⁵ and q are as defined above. ]

丄 Each step 1 to step 4 can be referred to the method described in Comprehensive Organic Transformation, by RC Lalock, VCH publisher Inc., 1989. Manufacturing method 10

Specific examples of the compound (17) include the following compounds (17-1) to (17-46). These compounds can be produced, for example, according to the method described in WOO 1/74774 and Comprehensive Organic Transformation, RC Laroque, VCH publisher Inc, 1989.

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LOT CT0 / C00Zdf / X3d Contract 00Z OAV

80 CT0 / C00Zdf / X3d Contract 00Z OAV 09

 (17-43) As the compound (14) and the compound (18), commercially available products can be used. When the compound of the present invention or an intermediate thereof has a functional group such as an amino group, a carboxy group, a hydroxyl group, an amidino group, a guanidino group, or an oxo group, the method for producing the compound of the present invention may be protected as necessary. It also includes a step of introducing a group or a step of deprotection. As a suitable protecting group, a protecting method, and a deprotecting method, a method described in Protective Groups in Organic Synthesis 2nd Edition (John Wiley & Sons, Inc., 1991) can be used.

For example, hydroxyl-protecting groups include tert-butyldimethylsilyl and methoxymethyl And a protecting group for the amino group include a tert-butyloxycarbonyl group, a benzyloxycarbonyl group and the like. Such a hydroxyl-protecting group can be removed by a reaction in a solvent such as aqueous methanol, aqueous ethanol, or aqueous tetrahydrofuran in the presence of an acid such as hydrochloric acid, sulfuric acid, or acetic acid. In the case of a tert-butyldimethylsilyl group, the reaction can be carried out in a solvent such as tetrahydrofuran in the presence of, for example, tetrabutylammonium fluoride. Removal of the protecting group for the amino group can be performed, for example, in the case of a tert-butyloxycarbonyl group, in the presence of an acid such as hydrochloric acid or trifluoroacetic acid, in a solvent such as aqueous tetrahydrofuran, methylene chloride, chloroform, or aqueous methanol. In the case of a benzyloxycarbonyl group, for example, the reaction can be carried out in the presence of an acid such as hydrobromic acid in a solvent such as acetic acid.

 When the carboxyl group is protected, the form of protection includes, for example, tert-ester, orthoester, acid amide and the like. The removal of such a protecting group is carried out in the case of tert-butyl ester, for example, by reacting in the presence of hydrochloric acid in a water-containing solvent, and in the case of the orthoester, for example, water-containing methanol, water-containing tetrahydrofuran, It is carried out by treating with an acid in a solvent such as water-containing 1,2-dimethoxetane and then with an alkali such as sodium hydroxide. In the case of an acid amide, for example, an acid such as hydrochloric acid or sulfuric acid is used. The reaction can be carried out in the presence of a solvent such as water, hydrated methanol, or hydrated tetrahydrofuran.

Prodrugs can be manufactured according to a conventional method. The xanthine compounds represented by the formula (I) include those having an optically active center, and therefore, they may be in the form of a racemate or an optically active form when an optically active starting material is used. Can be obtained at If necessary, the racemates obtained can be physically or chemically resolved into their optical antipodes by known methods. Preferably, a diastereomer is formed from a racemate by a reaction using an optically active resolving agent. Different diastereomers can be separated by known methods, for example, fractional crystallization. The xanthine compound and its prodrug can be converted into a salt by mixing with a pharmaceutically acceptable acid in a solvent such as water, methanol, ethanol, or acetone. Pharmaceutically acceptable acids include, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, and nitric acid, or acetic acid, propionic acid, oxalic acid, succinic acid, lactic acid, malic acid, tartaric acid, and citric acid And organic acids such as maleic acid, fumaric acid, methanesulfonic acid, p-toluenesulfonic acid, and ascorbic acid. The drug of the present invention can be applied to the treatment of various diseases due to its inhibitory effect on DPP-IV. The compounds described herein suppress postprandial hyperglycemia in pre-diabetic conditions, treat non-insulin-dependent diabetes, treat autoimmune diseases such as arthritis and rheumatoid arthritis, treat intestinal mucosal diseases, promote growth, and transplant. It is useful for suppressing rejection of organ pieces, treating obesity, treating eating disorders, treating HIV infection, suppressing cancer metastasis, treating benign prostatic hyperplasia, treating periodontitis, and treating osteoporosis. The xanthine compound of the present invention, a prodrug thereof or a pharmaceutically acceptable salt thereof can be used orally or parenterally (for example, intravenously, subcutaneously or intramuscularly) as a pharmaceutical composition when used for therapy. It can be administered by internal injection, topically, rectally, transdermally, or nasally. Examples of the composition for oral administration include tablets, capsules, pills, granules, powders, solutions, suspensions, and the like. Examples of compositions for parenteral administration include, for example, Aqueous injection or oily agent, ointment, cream, lotion, aerosol, suppository, patch and the like. These formulations are prepared using conventionally known techniques, and can contain nontoxic and inert carriers or excipients usually used in the field of formulation.

The dose will vary depending on the individual compound and on the disease, age, weight, sex, symptoms, administration route, etc. of the patient, but will usually be relative to an adult (body weight 50 _kg ) for the xanthine compound of the present invention. The prodrug or a pharmaceutically acceptable salt thereof is administered in an amount of 0.1 to 1000 mg / day, preferably 1 to 300 mg / day, once or twice or three times a day. Also, it can be administered once every several weeks to several weeks. Further, the xanthine compound of the present invention, a prodrug thereof or a pharmaceutically acceptable salt thereof can also be used in combination with another therapeutic agent for diabetes. Here, other antidiabetic agents that can be used in combination include, for example, insulin preparations, sulfonylureas, sulfonamides, insulin secretagogues, biguanides, hyalcosidase inhibitors, and insulin sensitizers. . Example

 Hereinafter, the ability to explain the present invention in further detail by reference examples, examples and test examples The present invention is not limited to these. In this specification, the following abbreviations may be used for simplification of the description.

 B o c: tert-butoxy canoleponinole group

 C b z: benzyloxycarponyl group Example 1

 1,3-Dimethyl-7- (2-methyl-5-fluorobenzyl) -8-((R) -3-aminoaminopiperidine-1) xanthine

下記分取条件下、 光学活性力ラムを用いて実施例 6の化合物を光学分割すること により、 実施例 1の化合物を 5. 0 mg得た。

By optically resolving the compound of Example 6 using an optically active ram under the following fractionation conditions, 5.0 mg of the compound of Example 1 was obtained.

 Preparative conditions:

 Column: CHIRALPAK AD-H (DAICEL) (2.0 cmOx 25.0 cm)

 Mobile phase: 34% 2-propanone Z65. 8% Hexane / 0.2% Jethylamine Detection wavelength (UV): 254 nm

 Flow rate: 5.0 ml / min

Retention time: 36.98 rain (CHIRALPAK AD-H: 34% 2-propanol / hexane Ζθ. 2 vo 13

1% Jethylamine)

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.16-7.12 (ra, 1Η), 6.89-6.84 (ra, 1H), 6.45-6.41 (m, 1H), 5.32 (d, J = 16.8 Hz, 1H), 5.27 (d, J = 16.8 Hz, 1H), 3.58 (s, 3H), 3.40-3.35 (m, 1H), 3.34 (s, 3H), 3.26-3.23 (m, 1H), 2.93-2.88 (m, 2H ), 2.74-2.68 (m, 1H), 2.33 (s, 3H), 1.95-1.88 (m, 1H), 1.75-1.68 (m, 1H), 1.60-1.56 (ra, 1H), 1.26-1.22 ( m, 1H).

MS (ESI +) 401 (M ++ l, 100%).

 1,3-dimethyl-7- (2-promo-5-fluorobenzyl) -8-((R) -3-aminopiperidine-toinole) xanthine

実施例 1と同様の方法で、実施例 7の化合物から実施例 2の化合物を 3.7 mg得た。 保持時間： 38.16 min (CHIRALPAK AD-H ： 34% 2-プロパノール/へキサン 0.2 vo 1 % ジェチルァミン）

In the same manner as in Example 1, 3.7 mg of the compound of Example 2 was obtained from the compound of Example 7. Retention time: 38.16 min (CHIRALPAK AD-H: 34% 2-propanol / hexane 0.2 vo 1% getylamine)

¾丽_{R (400 MHz, CDC1 3)} δ 7.58-7.54 (m, 1H), 6.93-6.87 (m, 1H), 6.59-6.55 (ra, 1H), 5.38 (d, J = 17.7 Hz, 1H), 5.34 (d, J = 17.7 Hz, 1H), 3.58 (s, 3H), 3.39-3.38 (m, 1H), 3.36 (s, 311), 3.26-3.22 (m, 1H), 2.94-2.90 (m, 211), 2.71-2.66 (m, 1H), 1.97-1.89 (m, 1H), 1.78--1.70 (m, 1H), 1.61-1.57 (m, 1H): 1.26-1.23 (m, 1H).

MS (ESI +) 465 (M ⁺ +1, 100%). Example 3

1,3-dimethyl-7- (2-methyl-5-fluorobenzyl) -8-{[(IS, 2R) -2-aminoaminohexynole] amino} xanthine

下記分取条件下、 光学活性カラムを用いて実施例 18の化合物を光学分割するこ とにより、 実施例 3の化合物を 6 mg得た。

By optically resolving the compound of Example 18 using an optically active column under the following fractionation conditions, 6 mg of the compound of Example 3 was obtained.

 Preparative conditions:

 Column: CHIRALPAK AD-H (DAICEL) (2.0 οηιφχ 25.0 cm)

 Mobile phase: 34% 2-propanol Z65.8% hexane Ζθ.2% Jetylamine Detection wavelength (UV): 254 nm

 Flow rate: 5.0 ml / min

 Retention time: 22.13 min (CHIRALPAK AD-H: 34% 2-propanol Z hexane / 0.2 vo 1% getylamine)

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.17-7.14 (m, 1H), 6.92-6.87 (m, 1H), 6.63-6.60 (m, 1H), 5.35 (s, 2H), 4.97 (d, J = 7.2 Hz, 1H), 3.84-3.78 (m, 1H), 3.55 (s, 3H), 3.37 (s, 3H), 2.99-2.96 (m, 1H), 2.33 (s, 3H), 1.70-1.66 (m , 1H), 1.59-1.56 (m, 1H), 1.40-1.25 (m, 6H).

 MS (ESI +) 415 (M ++ 1, 100%). Example 4

 1,3-Dimethyl-7- (2-methyl-5-fluorobenzyl) -8-((R) -3-Aminopiperidine-1-inole) xanthine

A solution of 1,3-dimethyl-7- (2-methyl-5-fluorobenzyl) -8-bromoxanthine (152 mg) and (R) -3-aminobiperidine (100 mg) in ethanol (6 ml) at 110 ° C Seal The mixture was heated and stirred in a tube for 20 hours. The reaction solution was cooled to 25 ° C, concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted three times with chloroform (30 ml). The organic layer was dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (developing solvent: chloroform / methanol = 100/1 to 20/1). Compound

(124 mg) was obtained as a white solid.

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.16-7.12 (m, 1H), 6.89-6.84 (m, 1H), 6.45-6.41

(m, 1H), 5.32 (d, J = 16.8 Hz, 1H), 5.27 (d, J = 16.8 Hz, 1H), 3.58 (s, 3H

), 3.40-3.35 (m, 1H), 3.34 (s, 3H), 3.26-3.23 (m, 1H), 2.93-2.88 (m, 2H), 2.74-2.68 (m, 1H), 2.33 (s, 3H ), 1.95—1.88 (m, 1H), 1.75—1.68 (m, 1H), 1.6 0-1.56 (ra, 1H), 1.26—1.22 (ra, 1H).

MS (ESI +) 401 (M ⁺ +1, 100%). Example 5

 1,3-Dimethyl-7- (2-co-mouth-5-fluoro-benzyl) -8-((R) -3-T-minopiperidine-1-inole) xanthine

 In the same manner as in Example 4, the compound of Example 5 was synthesized from the corresponding reference example compound.

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.40-7.36 (m, 1H), 6.98-6.93 (m, 1H), 6.61-6.58 (m, 1H), 5.38 (d, J = 17.6 Hz, 1H), 5.33 (d, J = 17.6 Hz, 1H), 3.58 (s, 3H), 3.40—3.38 (m, 1H), 3.35 (s, 3H), 3.25-3.22 (m, 1H), 2.94—2.91 (m, 2H ), 2.73-2.68 (m, 1H), 1.93—1.90 (m, 1H), 1.73—1.72 (m, 1H), 1.61—1.57 (m, 1H),

1.27-1.24 (m, 1H).

MS (ESI +) 421 (M ⁺ +1, 100%). Example 6 6

1,3-Dimethizole-7- (2-methyl-5-funoreo benzoinole)-8- (3-aminopiperidine-1-inole)

1,3-Dimethyl-7- (2-methyl-5-fluorobenzinole) -8-butamoxanthin (191 rag), 3-[(tert-butoxycarbinole) amino] piperidine (200 mg) in ethanol (6 ml) was heated and stirred in a sealed tube at 100 ° C for 30 hours. The reaction solution was cooled to 25 ° C. and concentrated under reduced pressure. The residue was purified by silica gel gel chromatography (developing solvent: chloroform / methanol = 200/1 to 75/1) to obtain the product. Next, 4N hydrochloric acid-dioxane solution (20 ml) was added to the dioxane solution (4 ml) of the product, and the mixture was stirred at 25 ° C for 3 hours. The reaction solution was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution (100 ml) was poured into the residue, and the mixture was extracted three times with Clonor Honolem (30 ml). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the compound of Example 6 (204 mg) as a white solid. _{¾ NMR (400 MHz, CDC1 3} ) δ 7.16-7.13 (m, 1H), 6.89-6.84 (m, 1H), 6.44-6.41 (m, 1H), 5.32 (d, J = 16.7 Hz, 1H), 5.26 (d, J = 16.7 Hz, 1H), 3.58 (s, 3H), 3.40-3.36 (m, 1H), 3.34 (s, 3H), 3.26-3.22 (m, 1H), 2.95—2.88 (m, 2H ), 2.75-2.69 (m, 1H), 2.33 (s, 3H), 1.95-1.88 (m, 1H), 1.71-1.69 (m, 1H), 1.6 2-1.58 (m, 1H), 1.26-1.21 ( m, 1H).

MS (ESI +) 401 (M ⁺⁺ 1, 100%). In the same manner as in Example 6, the compounds of Examples 7 to 10 were synthesized from the corresponding reference compounds.

Example 7

1,3-Dimethyl-7- (2-butamo-5-fluorobenzyl) -8- (3-aminopyridin-1-yl) xanthine 7

¾删_{R (400 MHz, CDC1 3)} δ 7.58-7.54 (tn, 1H), 6.93-6.88 (m, 1H), 6.59-6.56 (m, 1H), 5.38 (d, J = 17.0 Hz, 1H), 5.34 (d, J = 17.0 Hz, 1H), 3.58 (s, 3H) 3.40-3.38 (m, 1H), 3.36 (s, 3H), 3.26—3.22 (m, 1H), 2.93-2.88 (m, 2H ), 2.71-2.66 (m, 1H), 1.93-1.89 (m, 1H), 1.75-1.71 (m, 1H), 1.61-1.57 (m, 1H), 1.29-1.20 (m, 1H).

MS (ESI +) 465 (M ⁺ +1, 96%). Example 8

 1,3-Dimethyl-7- (2-kuguchi-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl) xanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.39-7.36 (m, 1H), 6.98-6.93 (ra, 1H), 6.61-6.58 (m, 1H), 5.38 (d, J = 17.6 Hz, 1H), 5.33 (d, J = 17.6 Hz, 1H), 3.58 (s, 3H), 3.40-3.38 (m, 1H), 3.36 (s, 3H), 3.25-3.22 (ra, 1H), 2.95-2.88 (m, 2H ),

2.72-2.67 (ra, 1H), 1.93—1.90 (m, 1H), 1.73-1.70 (m, 1H), 1.61—1.57 (ra, 1H), 1.25-1.23 (m, 1H).

MS (ESI +) 421 (M ++ 1, 100%).

1,3-Dimethyl-7- (2-methoxy-5-fluorobenzyl) -8- (3-aminopiperidine-1-yl ) Xanthine

_{¾ MR (400 MHz, CDC1 3} ) δ 6.95-6.90 (m, 1H), 6.83-6.81 (m, 1H), 6.53-6.49 (m, 1H), 5.36 (d, J = 17.2 Hz, 1H), 5.31 (d, J = 17.2 Hz, 1H), 3.86 (s, 3H), 3.57 (s, 3H), 3.42-3.37 (m, 1H), 3.35 (s, 3H), 3.29-3.24 (m, 1H) , 2.92 -2.87 (m, 2H), 2.73-2.67 (m, 1H), 1.94-1.88 (m, 1H), 1.75-1.68 (m, 1H), 1.60-1.56 (m, 1H), 1.26- 1.20 (m, 1H).

MS (ESI +) 417 (M ++ 1, 100%). Example 10

 1,3-Dimethyl-7- (2-trifluoromethyl-5-fluoromouth benzyl) -8- (3-T-minopiperidin-1_yl) xanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.74-7.71 (m, 1H), 7.09-7.05 (m, 1H), 6.66 (d, J = 9.0 Hz, 1H), 5.54 (s, 2H), 3.59 (s , 3H), 3.41-3.36 (m, 1H), 3.35 (s, 3H), 3.23-3.19 (m, 1H), 2.91-2.84 (m, 2H), 2.70-2.65 (m, 1H), 1.93-1.89 (m, 1H), 1.69–1.67 (m, 1H), 1.58–1.54 (ra, 1H), 1.25–1.21 (m, 1H).

MS (ESI +) 455 (M ++ 1, 100%). Example 1 1

1- (2-oxo-2-phenylethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8- ( 9

(R) _3-Aminobiperidine_1-Inole) xanthine

 1- (2-year-old oxo-2-phenenoletinole) -3-methinole 7— (2-methinole-5-funoleno-benzinole) -8-promoxanthin (242 rag) and (R) -tert-3 A solution of -butylbiperidine-3-ylcarbamate (200 mg) in ethanol (6 ml) was heated and stirred at 110 ° C in a sealed tube for 30 hours. The reaction solution was cooled to 25 ° C and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (developing solvent: chloroform / methanol = 200/1 to 75/1) to obtain the product (350 mg). Next, a 4 N hydrochloric acid dioxane solution (20 ml) was added to a dioxane solution (5 ml) of the product, and the mixture was stirred at 25 ° C for 3 hours. The reaction solution was concentrated under reduced pressure, a saturated aqueous sodium hydrogen carbonate solution (100 ml) was added to the residue, and the mixture was extracted twice with chloroform (50 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the compound of Example 11 (237 mg) as a white solid.

_{¾ NMR (400 MHz, CDC1 3} ) δ 8.00-7.97 (m, 2H), 7.59-7.56 (m, 1H), 7.50-7.44 (m, 2H), 7.13 (dd, J = 5.6, 8.3 Hz, 1H) , 6.88—6.84 (ra, 1H), 6.51 (dd, J = 2.5, 9.7 Hz, 1H), 5.40 (s, 2H), 5.30 (d, J = 16.8 Hz, 1H), 5.25 (d, J = 16 , 8 Hz, 1H), 3.60 (s, 3H), 3.45-3.38 (m, 1H), 3.30—3.23 (m, 1H), 2.95—2.91 (m, 2H), 2.76-2.71 (ra, 1H), 2.30 (s, 3H), 1.97-1.90 (m, 1H), 1.76-1.70 (m, 1H), 1.65-1.60 (m, 1H), 1.30-1.22 (m, 1H).

MS (ESI +) 505 (M ++ 1, 100%). In the same manner as in Example 11, the compounds of Examples 12 to 14 were synthesized from the corresponding reference compounds.

Example 12

1- (2-Naphthylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-((R) -3-aminopiperidine-1-inole) xanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.86 (s, 1H), 7.79-7.73 (m, 3H), 7.55 (dd, J = 1. 7, 8.4 Hz, 1H), 7.43-7.40 (m, 2H) , 7.14-7.12 (m, 1H), 6.90-6.87 (m, 1H), 6.50 (dd, J = 2.6, 9.8 Hz, 1H), 5.36-5.26 (m, 4H), 3.56 (s, 3H) , 3.39—3.35 (m, 1H), 3.25-3.22 (m, 1H), 2.92—2.86 (m, 2H), 2.73-2.68 (m, 1H), 2.32 (s, 3H), 1.94-1.88 (m, 1H) 1H), 1.75-1.68 (m, 1H), 1.62-1.55 (m, 1H), 1.25-1.19 (m, 1H).

MS (ESI +) 527 (M + + l, 100%). Example 1 3

 1_ (pyridine-2-ylmethyl) -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-((R) -3-aminopyridin-1-ynole) xanthine

^{X H NMR (400 MHz, CDC1} 3) δ 8.50 (d, J = 4.2 Hz, 1H), 7.60-7.56 (m, 1H), 7.17 (d, J = 7.8 Hz, 1H), 7.14-7.09 (m, 2H), 6.88-6.84 (ra, 1H), 6.48 (dd, J = 2.5, 9.8 Hz, 1H), 5.36-5.26 (m, 4H), 3.58 (s, 3H), 3.41-3.38 (m, 1H) , 3.26 —3.23 (m, 1H), 2.95-2.90 (m, 2H), 2.78—2.72 (m, 1H), 2.30 (s, 3H), 1.72—1.69 (m, 1H), 1.65—1.57 ( m, 2H), 1.29-1.25 (m, 1H).

1- (Isoquinoline-1-inolemethyl) -3-methyl-7- (2-methyl-5-fluorobenzinole) -8- ((R) -3-Aminopiperidine-1-yl) xanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 8.33 (d, J = 5.8 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.65-7.58 ( m, 2H), 7.48 (d, J = 5.7 Hz, 1H),

7.10-7.07 (m, 1H), 6.86-6.83 (m, 1H), 6.54 (dd, J = 2.5, 9.8 Hz, 1H), 5.8 2 (s, 2H), 5.33 (d, J = 17.1 Hz, 1H ), 5.28 (d, J = 17.1 Hz, 1H), 3.62 (s, 3H), 3.42-3.38 (ra, 1H), 3.28-3.23 (m, 1H), 2.94-2.90 (m, 2H), 2.76— 2.71 (m,

1H), 2.28 (s, 3H), 1.94-1.90 (ra, 1H), 1.75-1.70 (m, 1H), 1.61-1.55 (ra, 1H), 1.6-1.23 (ra, 1H).

MS (ESI +) 528 (M ++ 1, 100%). Example 15

 1- [2-oxo-2- (2-methoxypheninole) ethyl] -3-methyl-7- (2-methyl-5-phenolenebenzinole) -8- (3-aminopiperidine-1 -Yl) xanthine

1- [2-oxo-2- (2-methoxypheninole) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzyl) -8-bromoxanthine (258 mg) and 3-aminobiperidine A solution of the hydrochloride (346 mg) in ethanol (10 ml) was heated and stirred at 110 ° C in a sealed tube for 8 hours. The reaction solution was cooled to 25 ° C and concentrated under reduced pressure. The residue was dissolved in black-mouthed form (100 ml), and washed with 1N hydrochloric acid (100 ml), followed by saturated aqueous sodium hydrogen carbonate (100 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give the compound of Example 15 (186 mg). Obtained as a pale yellow solid.

_{¾ NMR (400 MHz, CDC1 3} ) β 7.91 (dd, J = 1.8, 7.8 Hz, 1H), 7.50-7.46 (m, 1H) 7.12 (dd, J = 5.7, 8.2 Hz, 1H), 7.01-6.96 ( m, 2H), 6.86-6.83 (m, 1H), 6.5

0 (dd, J = 2.6, 9.7 Hz, 1H), 5.34 (s, 2H), 5.31-5.23 (m, 2H), 3.93 (s, 3H) 3.59 (s, 3H), 3.41-3.37 (m, 1H ), 3.27-3.23 (m, 1H), 2.93—2.88 (m, 2H), 2.

75—2.69 (ra, 1H), 2.30 (s, 3H), 1.96—1.88 (m, 1H), 1.75—1.68 (m, 1H), 1.61—

1.59 (m, 1H), 1.26—1.23 (m, 1H).

 MS (ESI +) 535 (M ++ 1, 100%). In the same manner as in Example 15, the compounds of Examples 16 to 17 were synthesized from the corresponding reference examples.

 Example 16

 1- [2-oxo-2- (3-methoxyphenyle) ethyl] -3-methyl-7- (2-methynole-5-fluorobenzyl) -8- (3-aminopiperidine-1- Inole) Xanthine

 應 Response R (400 MHz, CDClg) δ 7.59-7.57 (ra, 1H), 7.50-7.49 (m, 1H), 7.39-7.35

(m, 1H), 7.14-7.11 (m, 2H), 6.87-6.84 (m, 1H), 6.52-6.49 (m, 1H), 5.38 (s, 2H), 5.30 (d, J = 16.8 Hz, 1H ), 5.25 (d, J = 16.8 Hz, 1H), 3.83 (s, 3H), 3.59 (s, 3H), 3.42-3.39 (m, 1H), 3.30-3.25 (m, 1H), 2.95-2.91 ( ra, 2H), 2.

76-2.70 (m, 1H), 2.30 (s, 3H), 1.96-1.90 (m, 1H), 1.75-1.70 (m, 1H), 1.62-

1.60 (m, 1H), 1.27-1.24 (m, 1H).

 MS (ESI +) 535 (M ++ 1, 100%). Example 17

1- [2-oxo-2- (4-methoxyphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluoro Undil) -8- (3-Aminopiperidine-1-inole) xanthine

_{¾ MR (400 MHz, CDC1 3} ) δ 7.98 - 7.95 (m, 2H), 7.12 (dd, J = 5.7, 8.3 Hz, 1H), 6.95-7.91 (m, 2H), 6.88-6.84 (m, 1H) , 6.50 (dd, J = 2.6, 9.7 Hz, 1H), 5.36 (s, 2H), 5.30 (d, J = 16.7 Hz, 1H), 5.25 (d, J = 16.7 Hz, 1H), 3.87 ( s, 3H), 3.59 (s, 3H), 3.42-3.38 (m, 1H), 3.29-3.23 (m, 1H), 2.96-2.89 (m, 2H), 2.75-2.70 (m, 1H), 2.29 ( s, 3H), 1.95-1.88 (m, 1H), 1.75-1.69 (m, 1H), 1.64-1.61 (m, 1H), 1.27—1.24 (m, 1H).

MS (ESI +) 535 (M ++ 1, 100%). Example 18

 1,3-Dimethyl-7- (2-methyl-5-fluoromethylbenzyl) -8-[(cis-2-Τminoxymethylhexamino) amino] xanthine

A solution of 1,3-dimethyl-7- (2-methyl-5-fluorobenzyl) -8-bromoxanthine (191 rag) and 1,2-cyclohexanediamine (171 mg) in N-methylpyrrolidinone (1.5 ml) was prepared. The mixture was heated and stirred in a sealed tube at 160 ° C for 10 hours. The reaction solution was cooled to 25 ° C., concentrated under reduced pressure, 5% carbonated water was added to the residue, and the mixture was extracted three times with chloroform (30 ml). The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. Toluene (1.0 ml) was added to the residue, and the mixture was purified by recrystallization to obtain the compound of Example 18 (182 mg) as a white solid. _{¾ NMR (400 MHz, CDC1 3} ) δ 7.17-7.13 (m, 1H), 6.91-6.86 (m, 1H), 6.63-6.60 (ra, 1H), 5.34 (s, 2H), 4.95 (d, J = 7.3 Hz, 1H), 3.83-3.77 (m, 1H), 3.55 (s, 3H), 3.37 (s, 3H), 2.98-2.96 (m, 1H), 2.32 (s, 3H), 1.68—1.20 (m , 8H). MS (ESI +) 415 (M ⁺⁺ 1, 100%) In the same manner as in Example 18, the compounds of Examples 19 to 22 were synthesized from the corresponding reference compounds.

Example 19

 1,3-dimethyl-7- (2-c-mouth-5-fluorobenzyl) -8 _ [(cis-2-amino-c-hexinole) amino] xanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.38-7.35 (m, 1H), 6.98-6.93 (ra, 1H), 6.79-6.76

(ra, 1H), 5.44 (s, 2H), 5.13 (d, J = 7.2 Hz, 1H), 3.86-3.82 (m, 1H), 3.54 (s, 3H), 3.38 (s, 3H), 3.04— 3.01 (m, 1H), 1.69—1.34 (m, 8H).

MS (ESI +) 435 (M ⁺ + l, 100%)

Example 20

 1,3-Dimethinole-7- (2-butoxy-5-funoleo benzoinole) -8-[(cis-2-aminocyclohexyl) amino] xanthine

_{XH NMR (400 MHz, CDC1 3} ) δ 7.56-7.53 (ra, 1H), 6.92-6.87 (m, 1H), 6.71-6.68 (m, 1H), 5.42 (s, 2H), 5.08 (d, J = 7.3 Hz, 1H), 3.86-3.82 (m, 1H), 3.55 ( 25 s, 3H), 3.37 (s, 3H), 3.04-3.03 (m, 1H), 1.60-1.35 (m, 8H).

MS (ESI +) 479 (M + + l, 100%) Example 21

 1,3-dimethyl-7- (2-methoxy-5-fluorobenzyl) -8-[(cis-2_aminocyclohexinole) amino] xanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.31-7.28 (m, 1H), 6.99-6.94 (m, 1H), 6.87-6.84 (m, 1H), 5.63 (d, J = 7.4 Hz, 1H), 5.30 (s, 2H), 3.93 (s, 3H), 3.90—3.88 (m, 1H), 3.49 (s, 3H), 3.41 (s, 3H), 3.16-3.14 (m, 1H), 1.64—1.38 (ra , 8H) .MS (ESI +) 431 (M ⁺ + l, 100%) Example 22

 1,3-dimethyl-7- (2-methyl-5-fluorobenzyl) -8-[(cis-2-amino-4,5-dimethoxyhexyl) amino] xanthin

_{¾ NMR (400 MHz, CDC1 3} ) 8 7.17-7.13 (m, 1H), 6.90-6.86 (m, 1H), 6.51-6.42 (m, 1H), 5.40 (d, J = 17.1 Hz, 1H), 5.30 (d, J = 17.1 Hz, 1H), 4.95 (brs, 1H), 3.75-3.73 (m, 1H), 3.55 (s, 3H), 3.37-3.35 (m, 9H), 3.50-2.50 (m, 2H ) 3.01-2.99 (m, 1H), 2.32 (s, 3H), 1.79--1.64 (m, 4H).

MS (ESI +) 475 (M ++ 1, 100%) Reference example 1

 1,3-dimethyl-7_ (3,5-difluorobenzyl) -8- (3-aminopiperidine-1-yl) xanthine

 1,3-Dimethinole-7- (3,5-difluorobenzyl) _8-promoxanthin (385 mg), 3_aminobiperidine hydrochloride (346 mg), and diisopropylethylamine (0.7 ml) in ethanol (6 ml) The solution was heated and stirred in a sealed tube at 100 ° C for 25 hours. After cooling the reaction solution to 25 ° C, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The aqueous solution was neutralized with a 4N aqueous NaOH solution and extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was washed with ethanol and dried to give the compound of Reference Example 1 (320 mg) as a white solid.

_{¾ NMR (400 MHz, CDC1 3} ) δ 6.75-6.69 (m, 3H), 5.33 (s, 2H), 3.55 (s, 3H), 3.39-3.37 (m, 1H), 3.37 (s, 3H), 3.26 -3.21 (m, 1H), 3.01-2.91 (ra, 2H), 2.7 6—2.72 (m, 1H), 1.99—1.95 (m, 1H), 1.82—1.63 (m, 2H), 1.33—1.24 (m , 1H). MS (ESI +) 405 (M ++ 1, 100%). Reference Example 2

 1,3-dimethyl-7- (2-methylbenzyl) -8- (3-aminopiperidine-1-yl) xanthine

In the same manner as in Example 6, the compound of Reference Example 2 was synthesized from the corresponding Reference Example Compound. 27

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.18-7.10 (m, 3H), 6.72 (d, J = 7.4 Hz, 1H), 5.3 8 (d, J = 16.5 Hz, 1H), 5.30 (d, J = 16.5 Hz, 1H), 3.57 (s, 3H), 3.39—3.35 (ra, 1H), 3.34 (s, 3H), 3.28—3.24 (ra, 1H), 2.94-2.84 (m, 2H), 2.72—2.67 (m, 1H), 2.36 (s, 3H), 1.90—1.87 (m, 1H), 1.68—1.66 (m, 1H), 1.59—1.56 (m, 1H), 1.27-1.21 (m, 1H).

MS (ESI +) 383 (M ⁺ +1, 100%). Reference example 3

 1,3-dimethyl-7- (2-methyl-5-fluorobenzinole) -8-bromoxanthine

窒素気流下、 8 -ブロモテオフィリン （1.29 g) のジメチルホルムアミド（20 ml)溶 液に対し、 5_フルォロ- 2 -メチルベンジルブ口ミ ド (1.07 g) および炭酸力リウム（0 .76 g)を加え、 25 °Cで 20時間攪拌した。 反応溶液に水 （200 ml)を加え、 1時間攪 拌した。 析出した固体をろ取して、 へキサン（100 ml)で洗浄し、 +分に減圧乾燥さ せることによって、 参考例 3の化合物 （1.84 g) を白色固体として得た。

Under a nitrogen stream, a solution of 8-bromotheophylline (1.29 g) in dimethylformamide (20 ml) was mixed with 5_fluoro-2-methylbenzylbutamide (1.07 g) and potassium carbonate (0.76 g). Was added and stirred at 25 ° C. for 20 hours. Water (200 ml) was added to the reaction solution, and the mixture was stirred for 1 hour. The precipitated solid was collected by filtration, washed with hexane (100 ml), and dried under reduced pressure for + minutes to obtain the compound of Reference Example 3 (1.84 g) as a white solid.

¾ NMR (400 MHz, DMSO- d ₆ ) δ 7.30-7.28 (ra, 1H), 7.06-7.01 (ra, 1H), 6.29-6.25 (m, 1H), 5.50 (s, 2H), 3.44 (s , 3H), 3.19 (s, 3H), 2.36 (s, 3H).

MS (ESI +) 381 (M ⁺⁺ 1, 100%). In the same manner as in Reference Example 3, the compounds of Reference Examples 4 to 9 were synthesized.

Reference example 4

1,3-dimethyl-7- (2-bromo-5-fluorobenzyl) -8-bromoxanthine

¾ NMR (400 MHz, DMSO-d ₆ ) δ 7.79-7.75 (m, 1H), 7.21-7.16 (m, 1H), 6.53-6.49

(m, 1H), 5.52 (s, 2H), 3.45 (s, 3H), 3.19 (s, 3H).

MS (ESI +) 445 (M ++ l, 47%). Reference Example 5

 1,3-Dimethyl-7_ (2-ku mouth-5-fluor mouth benzinole) -8-butane moxanthin

Hiring R (400 MHz, DMSO- d ₆ ) δ 7.64-7.60 (ra, 1Η), 7.28-7.20

3 (m, 1H), 5.63 (s, 2H), 3.44 (s, 3H), 3.19 (s, 3H).

MS (ESI +) 401 (M ⁺ +1, 61%). Reference Example 6

 1,3-Dimethinole-7- (2-methoxy-5-fluorobenzinole) -8-Bumoxanthin

¾ NMR (400 MHz, DMSO— d ₆ ) δ 7.16-7.05 (m, 2Η), 6.47 (dd, J = 2.9, 9.0 Hz 1H), 5.44 (s, 2H), 3.85 (s, 3H), 3.43 ( s, 3H), 3.19 (s, 3H). MS (ESI +) 397 (M ⁺ + l, 100%). Reference Example 7

 1,3-dimethyl-7_ (2-trifluoromethyl-5-fluorobenzyl) -8-bromoxanthine

¾ NMR (400 MHz, DMSO— d ₆ ) δ 7.94 (dd, J = 5.4, 8.7 Hz, 1H), 7.42-7.38 (m, 1H), 6.64-6.61 (in, 1H), 5.71 (s, 2H) , 3.46 (s, 3H), 3.19 (s, 3H).

MS (ESI +) 435 (M ⁺ +1, 84%). Reference Example 8

 1,3-dimethyl-7- (3,5-difluorobenzyl) -8-promoxanthin

_{¾ NMR (400 MHz, CDC1 3} ) δ 6.88-6.86 (m, 2H), 6.80-6.74 (ra, 1H), 5.53 (s, 2 H), 3.58 (s, 3H), 3.41 (s, 3H). Reference Example 9

1,3-dimethyl-7- (2-methylbenzyl) -8-bromoxanthine N

 -Br

 N

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.23-7.18 (ra, 2H), 7.12-7.08 (m, 1H), 6.47 (d J = 5.8 Hz, 1H), 5.57 (s, 2H), 3.61 (s, 3H), 3.36 (s, 3H), 2.45 (s, 3H). MS (ESI +) 363 (M ⁺ +1, 94%). Reference Example 10

 5-Fluoro-2-methoxybenzyl bromide

窒素気流下、 4-フルォロ- 2-メチルァエソール （1.40 g) の四塩化炭素 （20 ml) 溶液に対し、 N -プロモスクシンイミ ド （1.96 g) およびァゾビスイソプチロニトリ ル (20 mg)を加え、 80 °Cで 19時間攪拌した。 反応溶液を 25 °Cに冷却後、 クロ口ホル ム （100 ml)を加え、 さらに 0.5%炭酸ナトリゥム水溶液を加え、 クロロホノレムにて 抽出した。 有機層を無水硫酸ナトリウムで乾燥し、 ろ過後減圧濃縮することによつ て、 参考例 1 0の化合物 （2.34 g) を無色液体として得た。

Under a stream of nitrogen, a solution of 4-fluoro-2-methylaesole (1.40 g) in carbon tetrachloride (20 ml) was added to N-promosuccinimide (1.96 g) and azobisisobutyronitrile (20%). mg), and the mixture was stirred at 80 ° C for 19 hours. After the reaction solution was cooled to 25 ° C, chloroform (100 ml) was added, and a 0.5% aqueous sodium carbonate solution was further added, followed by extraction with chlorophonolem. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the compound of Reference Example 10 (2.34 g) as a colorless liquid.

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.08-7.04 (m, 1H), '6.98-6.95 (m, 1H), 6.81 (dd, J = 4.3, 9.0 Hz, 1H), 4.50 (s, 2H), 3.87 (s, 3H). Reference Example 1 1

ベンジル 3 - [ (tert-ブトキシカルボ二ノレ）ァミノ]ピぺリジン- 1-カルポキシレート (11. 69 g) のメタノール溶液 （250 ml) に対し、 10%パラジウム一炭素（50%含水） (8. 50 g) を加え、 水素雰囲気下、 25 °Cにて 7時間攪拌した。 触媒をろ別し、 有機 層を減圧濃縮した。 反応混合物に飽和重曹水 （100 ml) を加え、 クロ口ホルム（50 m 1)で 2回抽出を行った。 有機層を無水硫酸ナトリウムで乾燥し、 ろ過後減圧濃縮す ることによって、 参考例 1 1の化合物（9. 89 g)を白色固体として得た。 3 _ [(tert-ptoxypanol) amino] piperidine

To a methanol solution (250 ml) of benzyl 3-[(tert-butoxycarbinole) amino] piperidine-1-carboxylate (11.69 g) was added 10% palladium-carbon (50% water) ( 8.50 g) was added, and the mixture was stirred under a hydrogen atmosphere at 25 ° C for 7 hours. The catalyst was removed by filtration, and the organic layer was concentrated under reduced pressure. To the reaction mixture was added a saturated aqueous sodium bicarbonate solution (100 ml), and the mixture was extracted twice with a black form (50 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to obtain the compound of Reference Example 11 (9.89 g) as a white solid.

_{¾ NMR (400 MHz, CDC1 3} ) δ 3. 60-3. 53 (ra, 1H), 3. 07-3. 04 (m, 1H), 2. 85-2. 78 (m, 1H), 2 70-2.62 (ra, 1H), 2.56-2.48 (ra, 1H), 1.84-1 79 (ra, 1H), 1.70-1.66 (m, 1H ), 1.51-1.47 (m, 2H), 1.44 (s, 9H).

MS (ESI +) 201 (M ++ 1, 100%). Reference Example 1 2

Benzyl 3-[(tert-butoxycarboel) amino] piperidine-1-carboxylate

窒素気流下、 1- [ (ベンジルォキシ）力ルポニル]ピぺリジン- 3-カルボン酸 (11. 19 g) の tert-プチルアルコール溶液 (80 ml) に対し、 トリェチルァミン (6. 20 ml) 、 続いてジフエ二ルホスホリルアジド（12. 28 g)を加え、 80 °Cに昇温後、 10時間攪拌 した。 25 °Cに冷却し、 5%炭酸カリウム水溶液（100 ml)を加えた。 tert-プチルアル コールを減圧留去した後、残った溶液をクロロホルム（100 ml)で 2回抽出を行った。 有機層を無水硫酸ナトリウムで乾燥し、 ろ過後減圧濃縮した。 残渣をシリカゲル力 ラムクロマトグラフィー （展開溶媒：クロ口ホルム/メタノール = 20/1から 3/1) で 精製し、 参考例 12の化合物 (9.89 g)を得た。

Under a stream of nitrogen, a solution of 1-[(benzyloxy) propanol] piperidine-3-carboxylic acid (11.19 g) in tert-butyl alcohol (80 ml) was added to triethylamine (6.20 ml), followed by Diphenylphosphoryl azide (12.28 g) was added, and the mixture was heated to 80 ° C and stirred for 10 hours. After cooling to 25 ° C, a 5% aqueous potassium carbonate solution (100 ml) was added. After tert-butyl alcohol was distilled off under reduced pressure, the remaining solution was extracted twice with chloroform (100 ml). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (developing solvent: chromatoform / methanol = 20/1 to 3/1). Purification gave the compound of Reference Example 12 (9.89 g).

¾ Keio _{R (400 MHz, CDC1 3)} δ 7.36-7.28 (ra, 5H), 5.16 (d, J = 12.5 Hz, 1H), 5.

12 (d, J = 12.5 Hz, 1H), 4.63-4.55 (m, 1H), 3.75-3.65 (m, 1H), 3.52—3.45 (m, 1H), 3.36-3.25 (m, 2H), 1.90— 1.82 (m, 1H), 1.72—1.65 (m, 1H), 1.59—1.50

(m, 2H), 1.43 (s, 9H).

 MS (ESI +) 335 (M ++ l, 100%). Reference Example 13

、 ノ -[(Benzyloxy) carbol] piperidin c: -Din-3-carboxylic acid

, No

 _ n bz

 Under a stream of nitrogen, add ethyl acetate (15.30 g) in dichloromethane (300 ml).

At 0 ° C, triethylamine (14.86 ml) was added, followed by dropwise addition of benzyl carbonate (17.00 g), and then the temperature was raised to 25 ° C and stirred for 6 hours. Water (100 ml) and a 5% aqueous solution of citric acid (100 ml) were added to the reaction solution, and the mixture was extracted twice with chloroform (100 ml). Organic layer

15 was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. To a solution of the residue (18.63 g) in ethanol (200 ml) was added a 1N aqueous solution of sodium hydroxide (96 ml) at 0 ° C, followed by heating to 25 ° C and stirring for 12 hours. 2N Hydrochloric acid was added to adjust the liquid property to pH = 7, and then ethanol was distilled off under reduced pressure. Potassium carbonate was added to the remaining solution to adjust the pH to 10, and the mixture was extracted with diethyl ether. After adding 2N hydrochloric acid to the remaining aqueous solution to adjust the liquid property to _PH = 2,

20 Extracted twice with ethyl acetate (150 ral). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to obtain the compound of Reference Example 13 (14.54 g) as a white solid.

¾ 丽 R (400 MHz, CDCI3) δ 7.40-7.28 (m, 5H), 5.15 (d, J = 12.6 Hz, 1H), 5.11 (d, J = 12.4 Hz, 1H), 4.24-4.16 (m , 1H), 3.99-3.94 (m, 1H), 3.20-3.02 (25 ra, 1H), 2.96-2.89 (m, 1H), 2.56-2.6 (ra, 1H), 2.09-2.06 (ra, 1H ), 1.75-1.62 (m, 2H), 1.58-1.42 (m, 1H). Reference example 1 4

 1- (2-oxo-2-phenylethylenol) -3-methyl _7_ (2-methyl-5-fluorobenzyl)-8-bromoxanthine

 Under a nitrogen stream, potassium carbonate (332 tng) was added to a solution of 3-methyl-7- (2-methyl-5-fluorobenzyl) -8-bromoxanthine (734 tng) in dimethylformamide (10 ml), and the mixture was heated at 80 ° The temperature was raised to C, and the mixture was heated and stirred for 1 hour. Subsequently, a solution of α-bromoacetophenone (332 mg) in dimethylformamide (1 ml) was added dropwise, and after completion of the addition, the mixture was heated and stirred at 80 ° C. for 8 hours. The reaction solution was cooled to 25 ° C, water (100 ml) was added, and hexane (100 ml) was further added. The precipitated solid was collected by filtration and sufficiently dried under reduced pressure at 50 ° C. to obtain the compound of Reference Example 14 (800 mg) as a white solid.

Marauder R (400 MHz, DMS0-d ₆ ) δ 8.00-7.98 (ra, 2H), 7.62-7.58 (m, 1H), 7.50-7.47 (ra, 2H), 7.17-7.14 (m, 1H), 6.91-6.86 (m, 1H), 6.25—6.22 (m, 1H), 5.52 (s, 2H) , 5.41 (s, 2H), 3.63 (s, 3H), 2.37 (s, 3H).

MS (ESI +) 485 (M ⁺⁺ 1, 100%). In the same manner as in Reference Example 14, the compounds of Reference Examples 15 to 20 were synthesized from the corresponding Reference Example Compounds.

Reference example 1 5

1- (2-Naphthylmethyl) -3-methinole-7_ (2-Methinole-5-fluoromouth benzyl) -8-bromoxanthin

Ή丽_{R (400 MHz, CDC1 3)} δ 7. 87 (s, 1H), 7. 80-7. 75 (m, 3H), 7. 57-7. 54 (m, ), 7.44-7.42 (m, 2H), 7.20-7.16 (m, 1H), 6.90—6.87 (m, 1H), 6.21 (dd, J =

2.5, 9.5 Hz, 1H), 5.54 (s, 2H), 5.30 (s, 2H), 3.60 (s, 3H), 2.40 (s, 3H). MS (ESI +) 507 (M ⁺ +1, 91%) . Reference Example 16

 1- (pyridine-2-ylmethinole) -3-methinole-7- (2-methyl-5-fluorobenzinole) -8-bromoxanthine

_{¾ NMR (400 MHz, CDC1 3} ) δ 8.50-8.49 (m, 1H), 7.63-7.59 (m, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.15 (m, 2H), 6.91-6.88 (m, 1H), 6.23 (dd, J = 2.6, 9.6 Hz _: 1H), 5.54 (s, 2H), 5.29 (s, 2H), 3.62 (s, 3H), 2.36 (s, 3H).

MS (ESI +) 458 (M ⁺ +1, 98%). Reference Example 17

1- [2-oxo-2- (2-methoxyphenyl) ethyl] -3-methinole-7- (2-methyl-5-fluorobenzene / re) -8-promoxanthin

¾丽_{R (400 MHz, CDC1 3)} δ 7.92 (dd, J = 1.8, 7.8 Hz, 1H), 7.53-7.50 (ra, 1H), 7.19-7.15 (ra, 1H), 7.03-6.98 (ra, 2H ), 6.92—6.86 (m, 1H), 6.24 (dd, J = 2.6, 9.6 Hz, 1H), 5.52 (s, 2H), 5.35 (s, 2H), 3.94 (s, 3H), 3.62 (s, 3H), 2.36 (s, 3H).

MS (ESI +) 515 (M ⁺ +1, 86%). Reference Example 1 8

 1_ [2-oxo_2- (3-methoxyphenyl) ethyl] -3-methyl-7- (2-methyl-5-fluorobenzinole) -8-promoxanthin

¾丽_{R (400 MHz, CDC1 3)} δ 7.58 (d, J = 7.8 Hz, 1H), 7.50-7.49 (m, 1H), 7.3 9 (t, J = 7.9 Hz, 1H), 7.17-7.13 (tn , 2H), 6.91-6.88 (m, 1H), 6.25—6.22 (m, 1H), 5.52 (s, 2H), 5.39 (s, 2H), 3.84 (s, 3H), 3.63 (s, 3H), 2.37 (s, 3H)

MS (ESI +) 515 (M ++ 1, 100%). Reference Example 1 9

 1- [2-oxo-2- (4-methoxyphenyl) ethyl] -3--methinole-7- (2-methizole-5-fluorobenzyl)-8-bromoxanthine

¾ NMR (400 MHz, CDC1₃) δ 7.97 (d, J = 8.9 Hz, 2H)， 7.19-7.14 (m, 1H)， 6.9

_{¾ NMR (400 MHz, CDC1 3} ) δ 7.97 (d, J = 8.9 Hz, 2H), 7.19-7.14 (m, 1H), 6.9

5 (d, J = 8.9 Hz, 2H), 6.91-6.87 (m, 1H), 6.24 (dd, J = 2.6, 9.5 Hz, 1H),

5.51 (s, 2H), 5.37 (s, 2H), 3.88 (s, 3H), 3.63 (s, 3H), 2.36 (s, 3H).

MS (ESI +) 515 (M ++ 1, 91%). Reference example 20

1- (Isoquinoline-1-inolemethinole) -3-Methyl-7- (2-methyl-5-fluoromouth benzyl) -8-Promoxanthin

_{¾ NMR (400 MHz, CDC1 3} ) δ 8.31 (d, J = 5.7 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1 H), 7.81 (d, J = 8.0 Hz, 1H), 7.67-7.61 (m, 2H), 7.50 (d, J = 5.7 Hz, 1H), 7.14-7.12 (m, 1H), 6.89—6.86 (m, 1H), 6.30 (dd, J = 2.5, 9.6 Hz, 1H), 5.8 2 (s, 2H), 5.54 (s, 2H), 3.66 (s, 3H), 2.34 (s, 3H).

MS (ESI +) 508 (M ++ 1, 88%). Reference Example 21

 3-methyl-7- (2-methyl-5-fluoromethyl) -8-bromoxanthine

 Under a nitrogen stream, 3-methyl-8-promoxanthin (8.71 g) was added to dimethylformamide (1

(00 ml) solution, 5-fluoro-2-methylbenzyl bromide (7.58 g) and sodium hydrogen carbonate (3.57 g) were added, and the mixture was stirred at 25 ° C for 20 hours. Water (400 ml) was added to the reaction solution,

Stir for 1 hour. The precipitated solid was collected by filtration, washed with hexane (100 ml), and dried sufficiently under reduced pressure to obtain the compound of Reference Example 21 (11.64 g) as a white solid.

¾ NMR (400 MHz, DMS0-d ₆ ) δ 11.32 (s, 1H), 7.31-7.27 (ra, 1H), 6.32-6.29 (m,

1H), 6.31 (dd, J = 2.6, 9.9 Hz, 1H), 5.46 (s, 2H), 3.36 (s, 3H), 2.35 (s,

3H).

MS (ESI +) 367 (M ⁺ +1, 91%). Test Example 1

Of plasma dipeptidyl peptidase inhibitor against Φdipidyl peptidase Action

Dilute the plasma containing dipeptidyl peptidase with Assay buffer (25 mM Tris-HC1, 140 mM NaCl, 10 mM KC1, pH 7.9) and transfer 50 μl to the microassay plate. Added. Compound solution 1/1 was added, mixed and incubated at room temperature. The substrate (Glycyl-L-Proline 4-Methyl-Coumaryl-7-Amide, Peptide Research Laboratories) was diluted to 0.2 mM with Atsushi buffer, added with 501, stirred, and incubated at room temperature. The reaction was stopped by addition of 100% aqueous acetic acid solution. The fluorescence intensity at an excitation wavelength of 360 nm and a measurement wavelength of 460 nm was measured using a fluorescent plate reader. Before adding the base solution, add 25% aqueous acetic acid solution beforehand to stop the reaction. The fluorescence intensity of the compound-added well was interpolated, and the residual enzyme activity at the time of compound addition was calculated as a relative value. Based on the relative residual enzyme activity value when multiple concentrations of the compound were added, the concentration of the compound that inhibited the enzyme activity by 50% was determined as IC ₅ . It was calculated as a value.

1,3-dimethyl-7- (3,5-difluorobenzyl) _8- (3-aminopiperidine-1-), which is a compound described in the examples and a compound of the examples of TO 02/068420 as a comparative compound. (V) Kisanthin (Reference Example 1) was subjected to this test. The results are shown in Table 18.

Table 18 Compound ic ₅₀ (nM) Compound IC ₅₀ (nM) Compound of Example 1 2.8 Compound of Example 14 4.6

Compound of Example 2 1.8 Compound of Example 15 18.9

Compound of Example 3 4.1 Compound of Example 16 15.1

Compound of Example 5 9.0 Compound of Example 17 210.0

Compound of Example 67.0 Compound of Example 18 12.1

Compound of Example 75.0 Compound of Example 199.4

Compound of Example 8 5.0 Compound of Example 20 12.2

Compound of Example 9 26.0 Compound of Example 21 Compound 84.0

Compound of Example 10 19.0 Compound of Example 2 2 61.4

Example 11 Compound of 1 3.2 Compound of Reference Example 1 74.4

Compound of Example 12 2

Compound of Example 13 69.5

Test example 2

Effects of dipeptidyl peptidase inhibitors on oral glucose tolerance test in high-fat diet-loaded mice

The compound of Example 1 and the compound of Reference Example 2 (1,3-dimethyl-7- (2-methylbenzyl) -8- (3-aminopiperidine- 1_ I Le) xanthine) solution (respectively, lysed with 0.5% aqueous carboxymethylcellulose solution, 0. 1 _m0 l / ml solution was prepared) as 10 ml / kg (administered amount of compound 1. 0 mu mol / kg) orally. The control group received the same volume of a 0.5% carboxymethylcellulose aqueous solution. 30 minutes after administration of the test compound 0.5% carboxymethylcellulose aqueous solution, a volume of 10 ml / kg (2 g / kg as administered glucose) of a glucose solution dissolved in 0.2 g / ml with physiological saline Was orally administered. 15, 30, 60 and 1 from sugar load Twenty minutes later, blood was collected from the tail vein. The blood glucose level (mg / dl) of the blood sample was measured by Glucose CII Test Co. (Wako Pure Chemical Industries, Ltd.), and the area under the curve (mg / dl- min) was calculated. (However, the blood glucose level of the sample obtained by blood collection before the start of the test was used as the 0-minute blood glucose level.)

 The results are shown in Table 19. The compound of Example 1 significantly suppressed an increase in blood glucose as compared to the control group (p = 0.004). In addition, the compound of Example 1 showed a clearly superior blood glucose level-inhibiting effect even with respect to the compound of Reference Example 2.

Table 19 Standard deviation of the mean (mg / dl ■ min) Control group 27081 ± 3235

Compound administration group of Reference Example 2 24117 ± 3569

Compound administration group of Example 1 20967 ± 1097

Industrial applicability

 According to the present invention, a compound having high DPP-IV inhibitory activity or improved in safety, toxicity, and the like can be provided.

Claims

The scope of the claims 1. A xanthine compound represented by the following formula (I), a prodrug thereof, or a pharmaceutically acceptable salt thereof.

[Wherein, R ¹ is (1) a hydrogen atom, or (2) C w alkyl optionally substituted with one or more groups independently selected from A r ¹ — X— or A ¹ Represents a group, Ar ¹ represents an optionally substituted aryl group, an optionally substituted aromatic heterocyclic group, or an optionally substituted, aliphatic heterocyclic group,  X represents a single bond, an oxygen atom, one C (= 0) one, one S (O) m—, or _S (O) m—NH—,  m represents 0, 1, or 2, A ¹ is (may be in 1-3 amino substituents on the same carbon atom) a halogen atom, a hydroxyl group, Okiso group is substituted with Shiano group, a carboxy group, 1 or 2 identical or different 〇 ₃ § alkyl group May be a rubamoyl group, an alkoxy group, an amino group, a CH alkylamino group, a diCHalkylamino group, a hydroxyimino group. _6- anole coximinino group, acylamino group, alkoxycarbonylamino group, C ^ alkylthio group, CH alkylsulfinyl group, Cw alkylsulfonyl group. Represents DOO ₆ Anore Koki aryloxycarbonyl group, § reel sulfonyl group, an a cycloalkyl group or _alkyl carbonylation group,, R ² represents a hydrogen atom, an alkoxycarbonylmethyl group, or a C alkyl group, R ³ is a chlorine atom, a bromine atom, an iodine atom, a cyano group, a carboxy group, an optionally substituted amino group, an optionally substituted alkyl group, or an optionally substituted There alkylthio group, an optionally substituted alkylsulfinyl group, optionally substituted alkylsulfonyl - group, C ₂ _ ₆ alkenyl, c ₂ _ ₆ Arukieru group, optionally substituted C - ₆ alkyl Represents a carbonyl group, an optionally substituted alkoxy group, or an optionally substituted sorbamoyl group; One Y—NH ₂ has the following formula (A)

(In the formula, n represents 0, 1, or 2, and R ⁴ is present one or two times, and independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, an oxo group, or an optionally substituted Represents a mino group, an optionally substituted alkoxy group, an optionally substituted alkyl group, an optionally substituted phenyl group, or an optionally substituted benzyl group, or R ⁴ is 2 When they are present together, they together represent methylene or ethylene, and can combine with the two carbon atoms constituting the ring to form a bridged ring.) Or a group represented by the following formula (B)

(In the formula, q represents 0, 1, or 2, and R ⁵ is one or two and independently represents a hydrogen atom, a halogen atom, a hydroxyl group, a carboxy group, an oxo group, or a substituent. Good amino group, optionally substituted CH alkoxy group, optionally substituted alkyl group, optionally substituted alkoxycarbonyl group, optionally substituted rubamoyl group, optionally substituted Represents a phenyl group or a benzyl group which may be substituted, or, when two R ⁵ are present, represents methylene or ethylene together and is bonded to two carbon atoms constituting a ring. It can also form a bridged ring.) Represents a group represented by ] 2. — Y— NH ₂ is a group represented by the formula (A) and n is 1 or 2, or one Y—NH ₂ is a group represented by the formula (B), q 2. The xanthine compound according to claim 1, which is 1 or 2, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 3. _Y—NH ₂ is a group represented by the formula (A) and n is 1 or one Y—NH ₂ is a group represented by the formula (B) and q is 1 The xanthine compound according to claim 1, a prodrug thereof, or a pharmaceutically acceptable salt thereof. 4. The xanthine compound or prodrug thereof according to claim 1, wherein R ² is a methyl group, or a pharmaceutically acceptable salt thereof. 5. R ⁴ or R ⁵ is a hydrogen atom, a halogen atom, an optionally substituted Ci-e alkyl group, or, xanthine any crab of claims 1 to 4, an alkoxy group which may be substituted, The compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 6. The method according to claim 1, wherein R ³ is a chlorine atom, a bromine atom, an iodine atom, a methyl group, an ethyl group, a cyano group, a trifluoromethyl group, a methoxy group, a trifluoromethoxy group, or a difluoromethoxy group. Or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 7. R ¹ is, A r ¹ - X- in a substituted alkyl group; Ar ¹ is located in the heterocyclic group aromatic be is also good Ariru or substituted optionally substituted; is a single The xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, which is a bond, an oxygen atom, _C (= 0)-, or one S (O) m-. . 8. R ¹ is located at d_ ₂ alkyl group substituted with Ar over X-; Ar ¹ has not been a good I Ariru group or substituted or optionally substituted also to aromatic be heterocyclic group; X is 7. The xanthine compound or prodrug thereof, or a pharmaceutically acceptable salt thereof according to claim 1, which is a single bond or 1 C (= 0) —. 9. R ¹ is 2-position Ar ¹ - be Echiru group substituted with X-; Ar ¹ is an optionally substituted phenyl group, an optionally substituted pyridyl group, optionally substituted A quinolyl group or an optionally substituted isoquinolyl group; X is a single bond The xanthine compound according to any one of claims 1 to 6, or a prodrug thereof, or a pharmaceutically acceptable salt thereof. 10. R ¹ is A r ¹ - X- in be substituted methyl group; Ar ¹ is phenyl group but it may also be substituted, an optionally substituted pyridyl group, optionally quinolyl group which may be substituted Or a substituted isoquinolyl group; X is -C (= θ) one; the xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6; Salt. 1 1. A r ¹ Hue optionally substituted - xanthine compound according to any one of claims 1 to 10 is Le group or its prodrug or pharmaceutically acceptable salt thereof. 12. The xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 10, wherein Ar ¹ is a pyridyl group which may be substituted. 13. The xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, wherein R ¹ is a hydrogen atom or a methyl group. 14. The xanthine compound according to any one of claims 1 to 6, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein R ¹ is a methyl group. 15. The xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, wherein —Y—NH ₂ is represented by the following formula (C).

16. The xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 14, wherein ——Y—NH ₂ is represented by the following formula (D). One NH NH ₂ 17. The method according to claim 1, which is represented by the following formula (11), (11), (IV;), (V), (VI), (VI1), (VIII), or (IX). A xanthine compound or a prodrug thereof, or a pharmaceutically acceptable salt thereof.

 18. A dipeptidyl peptidase-IV inhibitor comprising, as an active ingredient, the xanthine compound according to any one of claims 1 to 17, a prodrug thereof, or a pharmaceutically acceptable salt thereof.  19. A therapeutic agent for diabetes comprising the xanthine compound according to any one of claims 1 to 17, a prodrug thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. 20. The therapeutic agent for diabetes according to claim 19, which is used in combination with another therapeutic agent for diabetes.