Compound having inhibitory activity against diacylglycerol kinase α and / or ζ, and pharmaceutical use thereof

Abstract

To provide a compound having inhibitory activity against DGKα and / or ζ, which can be used as an active ingredient in an agent for inhibiting the progression of, inhibiting the recurrence of, and / or for treating cancer or infectious diseases.SOLUTION: For example, a 5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine derivative having the following structure is shown.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to a compound represented by the below-described general formula (I) or a salt thereof, which has inhibitory activity against diacylglycerol kinase α and / or ζ (hereinafter, sometimes abbreviated as DGKα and / or ζ, or DGKα and / or DGKζ), and pharmaceutical uses thereof. [Background technology]

[0002] Diacylglycerol kinase (DGK) is a lipid kinase that phosphorylates diacylglycerol (DAG) and converts it to phosphatidic acid (PA). Ten isozymes are known to exist in mammals. All isozymes share a highly homologous catalytic region and a C1 domain that is homologous to protein kinase C (PKC). The C1 domain has a zinc finger-like structure rich in cysteine ​​and histidine, and is thought to bind to phorbol esters / DAG (Non-Patent Document 1).

[0003] In T cells, DAG is produced together with inositol triphosphate (IP3) by phospholipase Cγ1 (PLCγ1) activated by antigen stimulation via the T cell receptor (TCR). The DAG produced acts as a second messenger, activating multiple downstream signaling pathways, including Ras-MAPK, NF-κB, and the phosphatidylinositol triphosphate-Akt-mTOR pathway, leading to T cell activation.

[0004] DGKα and DGKζ are two major isozymes in T cells. Each of these isozymes negatively regulates T cell activation by controlling the intensity of DAG signaling downstream of TCR-mediated antigen stimulation. It is known that T cells lacking DGKα or DGKζ exhibit enhanced activation upon antigen stimulation, and that dual inhibition further enhances this activation (Non-Patent Documents 2-5). Furthermore, T cell activation mediated by DGK inhibition is known to be resistant to soluble immunosuppressive factors such as transforming growth factor (TGF)-β, adenosine, and prostaglandin E2 (PGE2), as well as to inhibitory signals mediated by PD-1 (Non-Patent Documents 4-6). It is also known that NK cell cytotoxicity against major histocompatibility complex (MHC) class I-deficient cells is enhanced by DGKζ deficiency (Non-Patent Document 7).

[0005] Therefore, drugs that inhibit either or both of DGKα and DGKζ are expected to enhance the activation of immune cells, including T cells, and be useful in treating diseases associated with immune dysfunction or immune evasion, such as cancer and infectious diseases.

[0006] Patent Document 1 describes a compound of the general formula (A):

[0007] [ka]

[0008] (In the formula, R 1A represents a halogen atom, a C1-4 alkyl group, etc., and R 2A represents a hydrogen atom, a halogen atom, etc., and R 3A represents a C1-4 alkyl group, and R 4A represents a hydrogen atom or a C1-4 alkyl group, and ring A A represents a C3-7 monocyclic carbocyclic ring, etc., and X A represents a nitrogen atom or a carbon atom, and T A represents a bond, etc., and U A is 1 to 5 R 7Aa 3- to 7-membered monocyclic ring, a C5-10 bridged carbocyclic ring or a 5- to 10-membered bridged heterocyclic ring (wherein R 7A represents a halogen atom, a C1-4 alkyl group, a hydroxyl group, an oxo group, a C1-4 alkoxy group, a C1-4 haloalkoxy group, a cyano group or a benzyloxy group, etc., and Y A represents bonds, etc., and W A represents a bond, etc., and Z A represents a methylene group or the like, qA represents an integer of 1 to 4, rA each represents an integer of 0 to 5, and tA represents an integer of 0 to 2. The definitions of the groups are excerpted as necessary.) It is described that a compound represented by the formula (I), its salt, its solvate, or a prodrug thereof is useful for treating urinary outflow disorders, cancer, interstitial pneumonia or pulmonary fibrosis, scleroderma, pain, fibromyalgia, rheumatoid arthritis, etc.

[0009] Patent Document 2 also describes a compound of the general formula (B):

[0010] [ka]

[0011] (In the formula, R 1B is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, 0 to 4 R 1aB C1-3 alkyl substituted with R 2B is a hydrogen atom, 0 to 4 R 2aB C1-3 alkyl substituted with R 3B is a hydrogen atom, a fluorine atom, a chlorine atom, a bromine atom, -CN, etc.; R 4B is -CH2R 4aB etc;R 5B -CN, 0~4 R gB mB represents 1 to 3. The definitions of the groups are excerpted as necessary.) or a salt thereof is described as being useful for treating viral infections and proliferative diseases such as cancer.

[0012] However, the compounds described below and salts thereof disclosed in the present invention are not described in any of the prior art. [Prior art documents] [Patent documents]

[0013] [Patent Document 1] International Publication No. 2012 / 005227 [Patent Document 2] International Publication No. 2020 / 006018 [Non-patent literature]

[0014] [Non-Patent Document 1] Rohan P Joshi, et.al., Int. J. Mol.Sci. 14(4), 6649-73 (2013) [Non-patent document 2] Benjamin A Olenchock, et. al., Nat Immunol. 7(11), 1174-81 (2006) [Non-patent document 3] Matthew J Riese, et. al., J Biol Chem. 286(7), 5254-65 (2011) [Non-patent document 4] Matthew J Riese, et. al., Cancer Res. 73(12), 3566-77 (2013) [Non-patent document 5] In-Young Jung, et. Al., Cancer Res. 78(16), 4692-4703 (2018) [Non-patent document 6] Weiqing Jing, et. al., Cancer Res. 77, 5676-86 (2017) [Non-Patent Document 7] Enjun Yang, et. Al., J Immunol. 197, 934-41 (2016) Summary of the Invention [Problem to be solved by the invention]

[0015] An object of the present invention is to provide a compound having inhibitory activity against DGKα and / or ζ. [Means for solving the problem]

[0016] As a result of intensive research aimed at solving the above-mentioned problems, the present inventors have found that a compound represented by the below-described general formula (I) or a salt thereof (hereinafter sometimes abbreviated as the compound of the present invention) has inhibitory activity against DGKα and / or ζ.

[0017] That is, the present invention mainly provides the following embodiments. [1] General formula (I)

[0018] [ka]

[0019] (In the formula, R 1 (1) 1 to 5 R 11 (2) methylene substituted with a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 12 (3) methylene substituted with a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R 13 (4) methylene substituted with a C2-4 alkenyl group optionally substituted with 1 to 5 R 14 represents a methylene substituted by a C2-4 alkynyl group which may be substituted by R 11 , R 12 , R 13 and R 14 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, or (6) a cyano group; 11 , R 12 , R 13 and R 14 may be the same or different, R 2 (1) 1 to 5 R 15 (2) a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R 16 or (3) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 17 represents a C1-4 alkyl group optionally substituted with R 15 , R 16 and R 17 are each independently (1) 1 to 5 R 18 (1) a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with (C1-8 alkyl)carbonyl group; (2) a (C1-8 alkyl)carbonyl group; (3) 1 to 5 R 19 (4) a C1-8 haloalkyl group, (5) a 5- or 6-membered carbocyclic ring, (6) a 5- or 6-membered heterocyclic ring, (7) a C1-4 alkylsulfonyl group, (8) a C2-4 alkenylsulfonyl group, (9) a C1-4 alkoxycarbonyl group, (10) a C1-4 haloalkylamino group, (11) a t-butyloxycarbonylamino group, or (12) a 5,5-dimethyl-2,4-dioxooxazolidin-3-yl group; Multiple R 15 , R 16 and R 17 may be the same or different, R 18 and R 19 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, or (6) a cyano group; Multiple R 18 and R 19 may be the same or different, R 3 is (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, (6) a C1-4 haloalkoxy group, (7) a cyano group, or (8) 1 to 5 R 20(9) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 21 a 3- to 15-membered heterocycle optionally substituted with (10)-NR 22 R 23 , (11)-OR 24 , (12)-CONR 25 R 26 (13) a (C1-8 alkyl)carbonyl group, (14) a C1-4 alkyl group substituted with 1 to 3 hydroxyl groups, or (15) a 1-(hydroxyimino)ethyl group; R 20 and R 21 are each independently: (1) 1 to 5 R 27 (1) a C1-4 alkyl group optionally substituted with (1-5), (2) a halogen atom, (3) 1 to 5 R 28 (4) a C cycloalkyl group optionally substituted with 1 to 5 R 27-1 (5) a C1-4 alkoxy group optionally substituted with (4), (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R 20 and R 21 may be the same or different, R 27 , R 27-1 and R 28 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R 27 , R 27-1 and R 28 may be the same or different, R 22 , R 23 and R 24 are each independently (1) a hydrogen atom, (2) 1 to 5 R 29 (3) a C alkyl group optionally substituted with 1 to 5 R 29-1 (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2(5) a C2-4 alkynyl group optionally substituted with 1 to 5 R 30 or (6) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 31 represents a 3- to 15-membered heterocycle optionally substituted by R 29 , R 29-1 , R 29-2 , R 30 and R 31 are each independently (1) 1 to 5 R 32 (1) a C1-4 alkyl group optionally substituted with (1-5), (2) a halogen atom, (3) 1 to 5 R 33 (4) a C cycloalkyl group optionally substituted with 1 to 5 R 34 (5) a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R 35 (6) a 5- to 6-membered heterocycle optionally substituted with 1 to 5 R 32-1 (7) a C1-4 alkoxy group optionally substituted with (4), (8) a hydroxyl group, (9) a carbamoyl group, or (10) a cyano group; Multiple R 29 , R 29-1 , R 29-2 , R 30 and R 31 may be the same or different, R 32 , R 32-1 , R 33 , R 34 and R 35 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R 32 , R 32-1 , R 33 , R 34 and R 35 may be the same or different, R 25 and R 26are each independently (1) a hydrogen atom, (2) 1 to 5 R 36 (3) a C alkyl group optionally substituted with 1 to 5 R 36-1 (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 36-2 (5) a C2-4 alkynyl group optionally substituted with 1 to 5 R 37 or (6) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 38 represents a 3- to 15-membered heterocycle optionally substituted by R 36 , R 36-1 , R 36-2 , R 37 and R 38 each independently represents (1) a C1-4 alkyl group, (2) a halogen, (3) a C3-8 cycloalkyl group, (4) a 5- or 6-membered carbocyclic ring, (5) a 5- or 6-membered heterocyclic ring, (6) a C1-4 alkoxy group, (7) a C1-4 haloalkyl group, (8) a C1-4 haloalkoxy group, (9) a hydroxyl group, (10) a carboxyl group, (11) a carbamoyl group, or (12) a cyano group; Multiple R 36 , R 36-1 , R 36-2 , R 37 and R 38 may be the same or different, R 4 represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; R 5 represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; X is a nitrogen atom or CR 7 represents X 1 , X 2 , and X 3 are each independently a nitrogen atom, CH, or CR 6 represents R 6 represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; R 6 If there are multiple R 6 may be the same or different, Y 1 is a nitrogen atom, or CR 8 represents Y 2 is a nitrogen atom, or CR 9 represents Y 3 is a nitrogen atom, or CR 10 represents R 7 represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R 8 represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R 9 represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R 10 is (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, (6) a C1-4 haloalkoxy group, (7) a hydroxyl group, (8) an amino group, (9) a carboxyl group, (10) a carbamoyl group, (11) a (C1-4 alkyl)aminocarbonyl group, (12) a di-(C1-4 alkyl)aminocarbonyl group, (13) -CO- (a 3- to 6-membered saturated heterocycle), or (14) -CONHR 39 or (15) a cyano group; R 39is (1) a C1-4 alkyl group substituted with a cyano group, (2) a C1-4 alkoxy group, (3) a C1-4 haloalkyl group, (4) a C1-4 haloalkoxy group, (5) a hydroxyl group, (6) an amino group, (7) a (C1-4 alkyl)amino group, (8) a di-(C1-4 alkyl)amino group, or (9) 1 to 5 R 40 or (10) 1 to 5 R 41 represents a 3- to 6-membered saturated heterocycle optionally substituted by R 40 and R 41 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, or (5) a C1-4 haloalkoxy group; Multiple R 40 and R 41 may be the same or different, r represents an integer of 0 to 3, and a plurality of R 4 may be the same or different, s represents an integer of 0 to 3, and a plurality of R 5 may be the same or different. wherein each hydrogen atom may be a deuterium atom or a tritium atom.) or a salt thereof; [2] A pharmaceutical composition containing the compound represented by formula (I) or a salt thereof according to [1]; [3] An agent for inhibiting the progression, inhibiting recurrence and / or treating a disease associated with DGKα and / or DGKζ, comprising the compound represented by general formula (I) according to [1] or a salt thereof. [Effects of the Invention]

[0020] The compound of the present invention has inhibitory activity against DGKα and / or ζ and can therefore be used, for example, as an active ingredient of an agent for inhibiting the progression, inhibiting the recurrence and / or treating cancer or infectious diseases. DETAILED DESCRIPTION OF THE INVENTION

[0021] In the present invention, "halogen" includes, for example, fluorine, chlorine, bromine and iodine atoms.

[0022] In the present invention, the "C1-4 alkyl group" includes methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, and 1,1-dimethylethyl groups.

[0023] In the present invention, "C1-4 alkyl groups substituted with hydroxyl groups" include hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxy-1-methylethyl, hydroxy-butyl, hydroxy-1-methylpropyl, hydroxy-2-methylpropyl, and hydroxy-1,1-dimethylethyl groups. In these examples, groups where the substitution position of the hydroxyl group is not specified are intended to encompass all positional isomers. For example, a hydroxy-1-methylpropyl group includes 1-hydroxy-1-methylpropyl, 2-hydroxy-1-methylpropyl, 3-hydroxy-1-methylpropyl, and 1-(hydroxymethyl)propyl groups. Furthermore, C1-4 alkyl groups substituted with multiple hydroxyl groups are not specifically disclosed, but are intended to encompass all positional isomers substituted with 2 or 3 hydroxyl groups.

[0024] In the present invention, the "C1-8 alkyl group" includes methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, heptyl, 1-methylhexyl, and the like. Examples of C alkyl groups include octyl, 2-methylhexyl, 3-methylhexyl, 4-methylhexyl, 5-methylhexyl, 1,1-dimethylpentyl, 2,2-dimethylpentyl, 3,3-dimethylpentyl, 4,4-dimethylpentyl, octyl, 1-methylheptyl, 2-methylheptyl, 3-methylheptyl, 4-methylheptyl, 5-methylheptyl, 6-methylheptyl, 1,1-dimethylhexyl, 2,2-dimethylhexyl, 3,3-dimethylhexyl, 4,4-dimethylhexyl, and 5,5-dimethylhexyl groups. Even if not specifically shown in these examples, any C alkyl group is included in the present invention. For example, 1,2-dimethylpropyl and 1-ethylpropyl groups are also included in the present invention as C alkyl groups. The same applies to C alkyl groups.

[0025] In the present invention, the "C2-4 alkenyl group" includes ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-ethyl-1-ethenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, and 2-methyl-2-propenyl groups.

[0026] In the present invention, the "C2-4 alkynyl group" includes ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, and 3-butynyl groups.

[0027] In the present invention, the "C1-4 haloalkyl group" includes fluoromethyl, fluoroethyl, fluoropropyl, fluoro-1-methylethyl, fluorobutyl, fluoro-1-methylpropyl, fluoro-2-methylpropyl, fluoro-1,1-dimethylethyl, difluoromethyl, difluoroethyl, difluoropropyl, difluoro-1-methylethyl, difluorobutyl, difluoro-1-methylpropyl, difluoro-2-methylpropyl, difluoro-1,1-dimethylethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoro-1-methylethyl, trifluorobutyl, trifluoro-1-methylpropyl, trifluoro-2-methylpropyl, trifluoro-1,1-dimethylethyl Examples of fluoro-1-methylpropyl include chloromethyl, chloroethyl, chloropropyl, chloro-1-methylethyl, chlorobutyl, chloro-1-methylpropyl, chloro-2-methylpropyl, chloro-1,1-dimethylethyl, dichloromethyl, dichloroethyl, dichloropropyl, dichloro-1-methylethyl, dichlorobutyl, dichloro-1-methylpropyl, dichloro-2-methylpropyl, dichloro-1,1-dimethylethyl, trichloromethyl, trichloroethyl, trichloropropyl, trichloro-1-methylethyl, trichlorobutyl, trichloro-1-methylpropyl, trichloro-2-methylpropyl, trichloro-1,1-dimethylethyl, and 1,1,1,3,3,3-hexafluoro-2-propyl groups. In this example, groups that do not specify the substitution position of halogen atoms are intended to encompass all positional isomers. For example, the fluoro-1-methylpropyl group includes 1-fluoro-1-methylpropyl, 2-fluoro-1-methylpropyl, 3-fluoro-1-methylpropyl, and 1-(fluoromethyl)propyl groups. In the examples, when the number of halogen atoms is not specified, the group is considered to include all the numbers of halogen atoms. For example, although not specifically exemplified, a heptafluoropropyl group and a nonafluoropropyl group are also included in the "C1-4 haloalkyl group" of the present invention.

[0028] In the present invention, examples of the "C1-4 haloalkyl group optionally substituted with a hydroxyl group" include fluoromethyl, fluoroethyl, fluoropropyl, fluoro-1-methylethyl, fluorobutyl, fluoro-1-methylpropyl, fluoro-2-methylpropyl, fluoro-1,1-dimethylethyl, difluoromethyl, difluoroethyl, difluoropropyl, difluoro-1-methylethyl, difluorobutyl, difluoro-1-methylpropyl, difluoro-2-methylpropyl, difluoro-1,1-dimethylethyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoro-1-methylethyl, trifluorobutyl, trifluoro-1-methylpropyl, trifluoro-2-methylpropyl, trifluoro-1,1-dimethylethyl, chloromethyl, chloroethyl, chloropropyl, chloro-1-methylethyl These include C1-4 haloalkyl groups not substituted with hydroxyl groups, including chlorobutyl, chloro-1-methylpropyl, chloro-2-methylpropyl, chloro-1,1-dimethylethyl, dichloromethyl, dichloroethyl, dichloropropyl, dichloro-1-methylethyl, dichlorobutyl, dichloro-1-methylpropyl, dichloro-2-methylpropyl, dichloro-1,1-dimethylethyl, trichloromethyl, trichloroethyl, trichloropropyl, trichloro-1-methylethyl, trichlorobutyl, trichloro-1-methylpropyl, trichloro-2-methylpropyl, trichloro-1,1-dimethylethyl, and hexafluoro-2-propyl groups, as well as C1-4 haloalkyl groups not substituted with hydroxyl groups in which at least one hydrogen atom is substituted with a hydroxyl group (e.g., hexafluoro-hydroxy-2-propyl group, etc.). In these examples, groups in which the substitution position of the halogen atom is not specified are intended to encompass all positional isomers. For example, a fluoro-1-methylpropyl group includes 1-fluoro-1-methylpropyl, 2-fluoro-1-methylpropyl, 3-fluoro-1-methylpropyl, and 1-(fluoromethyl)propyl groups. In this example, groups in which the number of halogen atoms substituted is not specified are considered to include all the numbers of halogen atoms substituted.For example, although not specifically exemplified, heptafluoropropyl and nonafluoropropyl groups are included in the "C1-4 haloalkyl group optionally substituted with a hydroxyl group" of the present invention. Among these examples, a C1-4 haloalkyl group that is not substituted with a hydroxyl group in which at least one hydrogen atom is substituted with a hydroxyl group is considered to include all positional isomers, all numbers of substitution of halogen atoms, and all numbers of substitution of hydroxyl groups, as long as it exists chemically stable, even if not specifically exemplified.

[0029] In the present invention, the "C1-8 haloalkyl group" includes fluoromethyl, fluoroethyl, fluoropropyl, fluoro-1-methylethyl, fluorobutyl, fluoro-1-methylpropyl, fluoro-2-methylpropyl, fluoro-1,1-dimethylethyl, fluoropentyl, fluoro-1-methylbutyl, fluoro-2-methylbutyl, fluoro-3-methylbutyl, fluoro-1,1-dimethylpropyl, fluoro-2,2-dimethylpropyl, fluorohexyl, fluoro-1-methylpentyl, fluoro-2-methylpentyl, fluoro fluoro-3-methylpentyl, fluoro-4-methylpentyl, fluoro-1,1-dimethylbutyl, fluoro-2,2-dimethylbutyl, fluoro-3,3-dimethylbutyl, fluoroheptyl, fluoro-1-methylhexyl, fluoro-2-methylhexyl, fluoro-3-methylhexyl, fluoro-4-methylhexyl, fluoro-5-methylhexyl, fluoro-1,1-dimethylpentyl, fluoro-2,2-dimethylpentyl, fluoro-3,3-dimethylpentyl, fluoro-4,4-dimethylpentyl, fluorooctyl, fluoro fluoro-1-methylheptyl, fluoro-2-methylheptyl, fluoro-3-methylheptyl, fluoro-4-methylheptyl, fluoro-5-methylheptyl, fluoro-6-methylheptyl, fluoro-1,1-dimethylhexyl, fluoro-2,2-dimethylhexyl, fluoro-3,3-dimethylhexyl, fluoro-4,4-dimethylhexyl, fluoro-5,5-dimethylhexyl, difluoromethyl, difluoroethyl, difluoropropyl, difluoro-1-methylethyl, difluorobutyl, difluoro-1-methylpropyl , difluoro-2-methylpropyl, difluoro-1,1-dimethylethyl, difluoropentyl, difluoro-1-methylbutyl, difluoro-2-methylbutyl, difluoro-3-methylbutyl, difluoro-1,1-dimethylpropyl, difluoro-2,2-dimethylpropyl, difluorohexyl, difluoro-1-methylpentyl, difluoro-2-methylpentyl, difluoro-3-methylpentyl, difluoro-4-methylpentyl, difluoro-1,1-dimethylbutyl, difluoro-2,2-dimethylbutyl, difluoro-3,3-Dimethylbutyl, difluoroheptyl, difluoro-1-methylhexyl, difluoro-2-methylhexyl, difluoro-3-methylhexyl, difluoro-4-methylhexyl, difluoro-5-methylhexyl, difluoro-1,1-dimethylpentyl, difluoro-2,2-dimethylpentyl, difluoro-3,3-dimethylpentyl, difluoro-4,4-dimethylpentyl, difluorooctyl, difluoro-1-methylheptyl, difluoro-2-methylheptyl, difluoro difluoro-3-methylheptyl, difluoro-4-methylheptyl, difluoro-5-methylheptyl, difluoro-6-methylheptyl, difluoro-1,1-dimethylhexyl, difluoro-2,2-dimethylhexyl, difluoro-3,3-dimethylhexyl, difluoro-4,4-dimethylhexyl, difluoro-5,5-dimethylhexyl, trifluoromethyl, trifluoroethyl, trifluoropropyl, trifluoro-1-methylethyl, trifluorobutyl, trifluoro-1- Methylpropyl, trifluoro-2-methylpropyl, trifluoro-1,1-dimethylethyl, trifluoropentyl, trifluoro-1-methylbutyl, trifluoro-2-methylbutyl, trifluoro-3-methylbutyl, trifluoro-1,1-dimethylpropyl, trifluoro-2,2-dimethylpropyl, trifluorohexyl, trifluoro-1-methylpentyl, trifluoro-2-methylpentyl, trifluoro-3-methylpentyl, trifluoro-4-methylpentyl, trifluoro-1,1-dimethylbutyl, trifluoro-2,2-dimethylbutyl, trifluoro-3,3-dimethylbutyl, trifluoroheptyl, trifluoro-1-methylhexyl, trifluoro-2-methylhexyl, trifluoro-3-methylhexyl, trifluoro-4-methylhexyl, trifluoro-5-methylhexyl, trifluoro-1,1-dimethylpentyl, trifluoro-2,2-dimethylpentyl, trifluoro-3,3-dimethylpentyl, trifluoro-4,4-dimethylpentyl, trifluorooctyl, trifluoro-1-methylheptyl, trifluoro-2-methylheptyl, trifluoro-3-methylheptyl, trifluoro-4-methylheptyl, trifluoro-5-methylheptyl, trifluoro-6-methylheptyl, trifluoro-1,1-dimethylhexyl, trifluoro-2,2-dimethylhexyl, trifluoro-3,3-dimethylhexyl, trifluoro-4,4-dimethylhexyl, trifluoro-5,5-dimethylhexyl, chloromethyl, chloroethyl, chloropropyl, chloro -1-Methylethyl, chlorobutyl, chloro-1-methylpropyl, chloro-2-methylpropyl, chloro-1,1-dimethylethyl, chloropentyl, chloro-1-methylbutyl, chloro-2-methylbutyl, chloro-3-methylbutyl, chloro-1,1-dimethylpropyl, chloro-2,2-dimethylpropyl, chlorohexyl, chloro-1-methylpentyl, chloro-2-methylpentyl, chloro-3-methylpentyl, chloro-4-methylpentyl, chloro-1,1-dimethylbutyl, chloro-2,2-dimethylbutyl, chloro-3,3-dimethyl butyl, chloroheptyl, chloro-1-methylhexyl, chloro-2-methylhexyl, chloro-3-methylhexyl, chloro-4-methylhexyl, chloro-5-methylhexyl, chloro-1,1-dimethylpentyl, chloro-2,2-dimethylpentyl, chloro-3,3-dimethylpentyl, chloro-4,4-dimethylpentyl, chlorooctyl, chloro-1-methylheptyl, chloro-2-methylheptyl, chloro-3-methylheptyl, chloro-4-methylheptyl, chloro-5-methylheptyl, chloro-6-methylheptyl, chloro-1, 1-dimethylhexyl, chloro-2,2-dimethylhexyl, chloro-3,3-dimethylhexyl, chloro-4,4-dimethylhexyl, chloro-5,5-dimethylhexyl, dichloromethyl, dichloroethyl, dichloropropyl, dichloro-1-methylethyl, dichlorobutyl, dichloro-1-methylpropyl, dichloro-2-methylpropyl, dichloro-1,1-dimethylethyl, dichloropentyl, dichloro-1-methylbutyl, dichloro-2-methylbutyl, dichloro-3-methylbutyl, dichloro-1,1-dimethylpropyl, dichloro-2,2-Dimethylpropyl, dichlorohexyl, dichloro-1-methylpentyl, dichloro-2-methylpentyl, dichloro-3-methylpentyl, dichloro-4-methylpentyl, dichloro-1,1-dimethylbutyl, dichloro-2,2-dimethylbutyl, dichloro-3,3-dimethylbutyl, dichloroheptyl, dichloro-1-methylhexyl, dichloro-2-methylhexyl, dichloro-3-methylhexyl, dichloro-4-methylhexyl, dichloro-5-methylhexyl, dichloro-1,1-dimethylpentyl, dichloro- 2,2-dimethylpentyl, dichloro-3,3-dimethylpentyl, dichloro-4,4-dimethylpentyl, dichlorooctyl, dichloro-1-methylheptyl, dichloro-2-methylheptyl, dichloro-3-methylheptyl, dichloro-4-methylheptyl, dichloro-5-methylheptyl, dichloro-6-methylheptyl, dichloro-1,1-dimethylhexyl, dichloro-2,2-dimethylhexyl, dichloro-3,3-dimethylhexyl, dichloro-4,4-dimethylhexyl, dichloro-5,5-dimethylhexyl, Trichloromethyl, trichloroethyl, trichloropropyl, trichloro-1-methylethyl, trichlorobutyl, trichloro-1-methylpropyl, trichloro-2-methylpropyl, trichloro-1,1-dimethylethyl, trichloropentyl, trichloro-1-methylbutyl, trichloro-2-methylbutyl, trichloro-3-methylbutyl, trichloro-1,1-dimethylpropyl, trichloro-2,2-dimethylpropyl, trichlorohexyl, trichloro-1-methylpentyl, trichloro-2-methylpentyl, trichlorohexyl Chloro-3-methylpentyl, trichloro-4-methylpentyl, trichloro-1,1-dimethylbutyl, trichloro-2,2-dimethylbutyl, trichloro-3,3-dimethylbutyl, trichloroheptyl, trichloro-1-methylhexyl, trichloro-2-methylhexyl, trichloro-3-methylhexyl, trichloro-4-methylhexyl, trichloro-5-methylhexyl, trichloro-1,1-dimethylpentyl, trichloro-2,2-dimethylpentyl, trichloro-3,3-dimethylpentyl, trichloro-4,Examples of fluoro-1-methylpropyl include 4-dimethylpentyl, trichlorooctyl, trichloro-1-methylheptyl, trichloro-2-methylheptyl, trichloro-3-methylheptyl, trichloro-4-methylheptyl, trichloro-5-methylheptyl, trichloro-6-methylheptyl, trichloro-1,1-dimethylhexyl, trichloro-2,2-dimethylhexyl, trichloro-3,3-dimethylhexyl, trichloro-4,4-dimethylhexyl, trichloro-5,5-dimethylhexyl, and 1,1,1,3,3,3-hexafluoro-2-propyl. In this example, groups that do not specify the substitution position of halogen atoms include all positional isomers. For example, the fluoro-1-methylpropyl group includes 1-fluoro-1-methylpropyl, 2-fluoro-1-methylpropyl, 3-fluoro-1-methylpropyl, and 1-(fluoromethyl)propyl groups. Even if not specifically shown in these examples, any C1-8 haloalkyl group is included in the present invention. For example, as C5 haloalkyl groups, fluoro-1,2-dimethylpropyl, fluoro-1-ethylpropyl, difluoro-1,2-dimethylpropyl, difluoro-1-ethylpropyl, trifluoro-1,2-dimethylpropyl, trifluoro-1-ethylpropyl, chloro-1,2-dimethylpropyl, chloro-1-ethylpropyl, dichloro-1,2-dimethylpropyl, dichloro-1-ethylpropyl, trichloro-1,2-dimethylpropyl, and trichloro-1-ethylpropyl groups are also included in the present invention. The same applies to C6-8 haloalkyl groups. In these examples, groups without a specified number of halogen atoms are considered to include all the halogen atom substitution numbers. For example, heptafluoropropyl and nonafluoropropyl groups are not specifically exemplified, but are included in the "C1-8 haloalkyl group" of the present invention.

[0030] In the present invention, the "(C1-8 alkyl)carbonyl group" includes methylcarbonyl, ethylcarbonyl, propylcarbonyl, 1-methylethylcarbonyl, butylcarbonyl, 1-methylpropylcarbonyl, 2-methylpropylcarbonyl, 1,1-dimethylethylcarbonyl, pentylcarbonyl, 1-methylbutylcarbonyl, 2-methylbutylcarbonyl, 3-methylbutylcarbonyl, 1,1-dimethylpropylcarbonyl, 2,2-dimethylpropylcarbonyl, hexylcarbonyl, 1-methylpentylcarbonyl, 2-methylpentylcarbonyl, 3-methylpentylcarbonyl, 4-methylpentylcarbonyl, 1,1-dimethylbutylcarbonyl, 2,2-dimethylbutylcarbonyl, 3,3-dimethylbutylcarbonyl, heptylcarbonyl, Included are 1-methylhexylcarbonyl, 2-methylhexylcarbonyl, 3-methylhexylcarbonyl, 4-methylhexylcarbonyl, 5-methylhexylcarbonyl, 1,1-dimethylpentylcarbonyl, 2,2-dimethylpentylcarbonyl, 3,3-dimethylpentylcarbonyl, 4,4-dimethylpentylcarbonyl, octylcarbonyl, 1-methylheptylcarbonyl, 2-methylheptylcarbonyl, 3-methylheptylcarbonyl, 4-methylheptylcarbonyl, 5-methylheptylcarbonyl, 6-methylheptylcarbonyl, 1,1-dimethylhexylcarbonyl, 2,2-dimethylhexylcarbonyl, 3,3-dimethylhexylcarbonyl, 4,4-dimethylhexylcarbonyl, and 5,5-dimethylhexylcarbonyl groups. Even if not specifically shown in these examples, any (C1-8 alkyl)carbonyl group is included in the present invention. For example, as a C5 alkylcarbonyl group, 1,2-dimethylpropylcarbonyl and 1-ethylpropylcarbonyl groups are also included in the present invention. The same applies to C6-8 alkylcarbonyl groups.

[0031] In the present invention, the term "C1-4 alkoxycarbonyl group" includes methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, 1-methylethoxycarbonyl, butoxycarbonyl, 1-methylpropoxycarbonyl, 2-methylpropoxycarbonyl, and 1,1-dimethylethoxycarbonyl groups.

[0032] In the present invention, the "(C1-4 alkyl)aminocarbonyl group" includes methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, 1-methylethylaminocarbonyl, butylaminocarbonyl, 1-methylpropylaminocarbonyl, 2-methylpropylaminocarbonyl, and 1,1-dimethylethylaminocarbonyl groups.

[0033] In the present invention, the "di-(C1-4 alkyl)amino group" includes dimethylamino, diethylamino, dipropylamino, di(1-methylethyl)amino, dibutylamino, di(1-methylpropyl)amino, di(2-methylpropyl)amino, and di(1,1-dimethylethyl)amino groups.

[0034] In the present invention, examples of the "C1-4 haloalkylamino group" include fluoromethylamino, fluoroethylamino, fluoropropylamino, fluoro-1-methylethylamino, fluorobutylamino, fluoro-1-methylpropylamino, fluoro-2-methylpropylamino, fluoro-1,1-dimethylethylamino, difluoromethylamino, difluoroethylamino, difluoropropylamino, difluoro-1-methylethylamino, difluorobutylamino, difluoro-1-methylpropylamino, difluoro-2-methylpropylamino, difluoro-1,1-dimethylethylamino, trifluoromethylamino, trifluoroethylamino, trifluoropropylamino, trifluoro-1-methylethylamino, trifluorobutylamino, trifluoro-1-methylpropylamino, trifluoro-2-methylpropyl ... These include trifluoro-1,1-dimethylethylamino, chloromethylamino, chloroethylamino, chloropropylamino, chloro-1-methylethylamino, chlorobutylamino, chloro-1-methylpropylamino, chloro-2-methylpropylamino, chloro-1,1-dimethylethylamino, dichloromethylamino, dichloroethylamino, dichloropropylamino, dichloro-1-methylethylamino, dichlorobutylamino, dichloro-1-methylpropylamino, dichloro-2-methylpropylamino, dichloro-1,1-dimethylethylamino, trichloromethylamino, trichloroethylamino, trichloropropylamino, trichloro-1-methylethylamino, trichlorobutylamino, trichloro-1-methylpropylamino, trichloro-2-methylpropylamino, and trichloro-1,1-dimethylethylamino. In these examples, when the substitution position of the halogen atom is not specified, all positional isomers are included. For example, a fluoro-1-methylpropylamino group includes 1-fluoro-1-methylpropylamino, 2-fluoro-1-methylpropylamino, 3-fluoro-1-methylpropylamino, and 1-(fluoromethyl)propylamino groups.

[0035] In the present invention, the term "di-(C1-4 alkyl)aminocarbonyl group" includes dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, di(1-methylethyl)aminocarbonyl, dibutylaminocarbonyl, di(1-methylpropyl)aminocarbonyl, di(2-methylpropyl)aminocarbonyl, and di(1,1-dimethylethyl)aminocarbonyl groups. It also includes di-(C1-4 alkyl)aminocarbonyl groups substituted with different C1-4 alkyls, such as N-methyl-N-ethylaminocarbonyl group.

[0036] In the present invention, the term "C1-4 alkoxy group" includes methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy, and 1,1-dimethylethoxy groups.

[0037] In the present invention, the "C1-4 haloalkoxy group" includes fluoromethoxy, fluoroethoxy, fluoropropoxy, fluoro-1-methylethoxy, fluorobutoxy, fluoro-1-methylpropoxy, fluoro-2-methylpropoxy, fluoro-1,1-dimethylethoxy, difluoromethoxy, difluoroethoxy, difluoropropoxy, difluoro-1-methylethoxy, difluorobutoxy, difluoro-1-methylpropoxy, difluoro-2-methylpropoxy, difluoro-1,1-dimethylethoxy, trifluoromethoxy, trifluoroethoxy, trifluoropropoxy, trifluoro-1-methylethoxy, trifluorobutoxy, trifluoro-1-methylpropoxy, trifluoro-2-methylpropoxy, These include trifluoro-1,1-dimethylethoxy, chloromethoxy, chloroethoxy, chloropropoxy, chloro-1-methylethoxy, chlorobutoxy, chloro-1-methylpropoxy, chloro-2-methylpropoxy, chloro-1,1-dimethylethoxy, dichloromethoxy, dichloroethoxy, dichloropropoxy, dichloro-1-methylethoxy, dichlorobutoxy, dichloro-1-methylpropoxy, dichloro-2-methylpropoxy, dichloro-1,1-dimethylethoxy, trichloromethoxy, trichloroethoxy, trichloropropoxy, trichloro-1-methylethoxy, trichlorobutoxy, trichloro-1-methylpropoxy, trichloro-2-methylpropoxy, and trichloro-1,1-dimethylethoxy. In these examples, groups in which the substitution position of the halogen atom is not specified include all positional isomers. For example, a fluoro-1-methylpropoxy group includes 1-fluoro-1-methylpropoxy, 2-fluoro-1-methylpropoxy, 3-fluoro-1-methylpropoxy, and 1-(fluoromethyl)propoxy groups.

[0038] In the present invention, the "(C1-4 alkyl)amino group" includes methylamino, ethylamino, propylamino, 1-methylethylamino, butylamino, 1-methylpropylamino, 2-methylpropylamino, and 1,1-dimethylethylamino groups.

[0039] In the present invention, the term "3- to 15-membered carbocyclic ring" includes monocyclic, bicyclic, or tricyclic unsaturated, partially saturated, or saturated 3- to 15-membered carbocyclic rings. Examples of monocyclic, bicyclic, or tricyclic unsaturated 3- to 15-membered carbocyclic rings include benzene, pentalene, naphthalene, azulene, phenanthrene, anthracene, acenaphthylene, and biphenylene rings. Examples of monocyclic, bicyclic, or tricyclic partially saturated or saturated 3- to 15-membered carbocyclic rings include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexene, cyclopentadiene, cyclohexadiene, indene, dihydroindene (indane), fluorene, perhydropentalene, perhydroindene, perhydronaphthalene, perhydroazulene, perhydrofluorene, perhydrophenanthrene, perhydroanthracene, perhydroacenaphthylene, perhydrobiphenylene, bicyclo[1.1.1]pentane, bicyclo[3.2.1]octane, spiro[3.5]nonane, spiro[3.3]heptane, and adamantane rings.

[0040] In the present invention, the term "3- to 15-membered heterocycle" includes a monocyclic, bicyclic, or tricyclic unsaturated, partially saturated, or saturated 3- to 15-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom. Examples of the monocyclic, bicyclic, or tricyclic unsaturated 3- to 15-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom include pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, oxepin, oxazepine, thiophene, thiaine (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, oxadiazole, and oxaa. Examples of the ring include azine, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine, thiadiazine, thiazepine, thiadiazepine, indole, isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole, quinoline, isoquinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, benzoxazole, benzoxadiazole, benzothiazole, benzimidazole, carbazole, and acridine ring. Examples of monocyclic, bicyclic, or tricyclic partially saturated or saturated 3- to 15-membered heterocycles containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom include aziridine, oxirane, azetidine, oxetane, thiirane, thietane, pyrroline, pyrrolidine, imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, pyrazoline, pyrazolidine, piperidine, piperazine, tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiain (dihydrothiopyran), tetrahydrothiain (tetrahydrothiopyran), oxazoline (dihydrooxazole), oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole, oxadiazoline (dihydrooxadiazole),Oxadiazolidine (tetrahydrooxadiazole), thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole), dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine, indoline, isoindoline, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzothiophene, dihydroisobenzothiophene, perhydroisobenzothiophene, dihydroindazole, perhydroindazole, Dihydroquinoline, tetrahydroquinoline, perhydroquinoline, dihydroisoquinoline, tetrahydroisoquinoline, perhydroisoquinoline, dihydrophthalazine, tetrahydrophthalazine, perhydrophthalazine, dihydronaphthyridine, tetrahydronaphthyridine, perhydronaphthyridine, dihydroquinoxaline, tetrahydroquinoxaline, perhydroquinoxaline, dihydroquinazoline, tetrahydroquinazoline, perhydroquinazoline, dihydrocinnoline, tetrahydrocinnoline, perhydrocinnoline, dihydrobenzoxazoline perhydrobenzoxazole, dihydrobenzothiazole, perhydrobenzothiazole, dihydrobenzimidazole, perhydrobenzimidazole, benzoxazepine, benzoxadiazepine, benzothiazepine, benzothiadiazepine, benzazepine, benzodiazepine, indolooxoazepine, indolotetrahydrooxazepine, indolooxadiazepine, indolotetrahydrooxadiazepine, indolothiazepine, indolotetrahydrothiazepine, indolothiadiazepine, indolotetrahydrothiazepine indoloazepine, indolotetrahydroazepine, indolodiazepine, indolotetrahydrodiazepine, benzofurazan, benzothiadiazole, benzotriazole, camphor, imidazothiazole, dihydrocarbazole, tetrahydrocarbazole, perhydrocarbazole, dihydroacridine, tetrahydroacridine, perhydroacridine, dioxolane, dioxane, dioxazine, chroman, perhydroazepine, perhydrodiazepine, perhydrothiepine, perhydrooxazepine, perhydrooxadiazepine,Examples include perhydrothiazepine and perhydrothiadiazepine rings.

[0041] In the present invention, the "3- to 15-membered heterocycle" also includes bridged rings and spiro rings. Examples of bridged 3- to 15-membered heterocycles include 8-azabicyclo[3.2.1]octane rings. Examples of spiro rings include 1-oxa-7-azaspiro[4.4]nonane and 2-azaspiro[3.3]heptane.

[0042] In the present invention, the term "5- or 6-membered carbocyclic ring" includes monocyclic unsaturated, partially saturated, or saturated 5- or 6-membered carbocyclic rings. Examples of monocyclic unsaturated 5- or 6-membered carbocyclic rings include cyclopentadiene and benzene rings. Examples of monocyclic partially saturated or saturated 5- or 6-membered carbocyclic rings include cyclopentane, cyclohexane, cyclopentene, cyclohexene, and cyclohexadiene rings.

[0043] In the present invention, the term "5- or 6-membered heterocycle" includes a monocyclic unsaturated, partially saturated, or saturated 5- or 6-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom. Examples of the monocyclic unsaturated 5- or 6-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom include pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, furan, pyran, thiophene, thiaine (thiopyran), oxazole, isoxazole, thiazole, isothiazole, oxadiazole, oxazine, oxadiazine, thiadiazole, thiazine, and thiadiazine rings. Examples of the monocyclic partially saturated or saturated 5- or 6-membered heterocyclic ring containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom include pyrroline, pyrrolidine, imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, pyrazoline, pyrazolidine, piperidine, piperazine, tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiaine (dihydrothiaine), ... Examples of suitable rings include tetrahydrothiopyran, tetrahydrothiaine (tetrahydrothiopyran), oxazoline (dihydrooxazole), oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole, oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahydrooxadiazole), thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole), dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine, dioxolane, dioxane, and dioxazine rings.

[0044] In the present invention, the term "5- to 7-membered heterocycle" includes a monocyclic unsaturated, partially saturated, or saturated 5- to 7-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom. Examples of the monocyclic unsaturated 5- to 6-membered heterocycle containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms, and / or 1 sulfur atom include pyrrole, imidazole, triazole, tetrazole, pyrazole, pyridine, pyrazine, pyrimidine, pyridazine, azepine, diazepine, furan, pyran, thiophene, thiain (thiopyran), thiepine, oxazole, isoxazole, thiazole, isothiazole, oxadiazole, oxazine, oxadiazine, oxazepine, oxadiazepine, thiadiazole, thiazine, thiazine, thiazepine, and thiadiazepine ring. Examples of monocyclic partially saturated or saturated 5- to 7-membered heterocyclic rings containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom include pyrroline, pyrrolidine, imidazoline, imidazolidine, triazoline, triazolidine, tetrazoline, tetrazolidine, pyrazoline, pyrazolidine, piperidine, piperazine, tetrahydropyridine, tetrahydropyrimidine, tetrahydropyridazine, dihydrofuran, tetrahydrofuran, dihydropyran, tetrahydropyran, dihydrothiophene, tetrahydrothiophene, dihydrothiaine (dihydrothiopyran), tetrahydrothiaine (tetrahydrothiopyran), oxazoline (di ... Examples of the perhydrooxazole ring include oxazolidine (tetrahydrooxazole), dihydroisoxazole, tetrahydroisoxazole, oxadiazoline (dihydrooxadiazole), oxadiazolidine (tetrahydrooxadiazole), thiazoline (dihydrothiazole), thiazolidine (tetrahydrothiazole), dihydroisothiazole, tetrahydroisothiazole, morpholine, thiomorpholine, dioxolane, dioxane, dioxazine, perhydroazepine, perhydrodiazepine, perhydrothiepine, perhydrooxazepine, perhydrooxadiazepine, perhydrothiazepine, and perhydrothiadiazepine ring.

[0045] In the present invention, the "3- to 6-membered saturated heterocycle" includes aziridine, oxirane, azetidine, oxetane, thiirane, thietane, pyrrolidine, imidazolidine, triazolidine, tetrazolidine, pyrazolidine, piperidine, piperazine, tetrahydrofuran, tetrahydropyran, tetrahydrothiophene, tetrahydrothiaine (tetrahydrothiopyran), oxazolidine (tetrahydrooxazole), tetrahydroisoxazole, oxadiazolidine (tetrahydrooxadiazole), thiazolidine (tetrahydrothiazole), tetrahydroisothiazole, morpholine, thiomorpholine, dioxolane, and dioxane rings.

[0046] In the present invention, the "5- to 7-membered nitrogen-containing saturated heterocycle" includes pyrrolidine, imidazolidine, triazolidine, tetrazolidine, pyrazolidine, piperidine, piperazine, oxazolidine (tetrahydrooxazole), tetrahydroisoxazole, oxadiazolidine (tetrahydrooxadiazole), thiazolidine (tetrahydrothiazole), tetrahydroisothiazole, morpholine, thiomorpholine, perhydroazepine, perhydrodiazepine, perhydrothiepine, perhydrooxazepine, perhydrooxadiazepine, perhydrothiazepine, and perhydrothiadiazepine, and a 2-azaspiro[3.3]heptane ring.

[0047] In the present invention, the "C3-6 cycloalkyl group" includes cyclopropane, cyclobutane, cyclopentane, and cyclohexane rings.

[0048] In the present invention, the "(C3-6 cycloalkyl)carbonyl group" includes cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, and cyclohexylcarbonyl groups.

[0049] In the present invention, the "C3-8 cycloalkyl group" includes cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, and cyclooctane rings.

[0050] In the present invention, the "C1-4 alkylsulfonyl group" includes methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methylethylsulfonyl, butylsulfonyl, 1-methylpropylsulfonyl, 2-methylpropylsulfonyl, and 1,1-dimethylethylsulfonyl groups.

[0051] In the present invention, the "C2-4 alkenylsulfonyl group" includes ethenylsulfonyl, 1-propenylsulfonyl, 2-propenylsulfonyl, 1-methylethenylsulfonyl, 1-butenylsulfonyl, 2-butenylsulfonyl, 3-butenylsulfonyl, 1-ethyl-1-ethenylsulfonyl, 1-methyl-1-propenylsulfonyl, 2-methyl-1-propenylsulfonyl, 1-methyl-2-propenylsulfonyl, and 2-methyl-2-propenylsulfonyl groups.

[0052] In the present invention, R 1 Preferably, (1) 1 to 5 R 11 or (2) methylene substituted with a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 12 and more preferably, methylene substituted with a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R 11 and more preferably, methylene substituted with a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R 11 and methylene substituted with benzene which may be substituted with .

[0053] In the present invention, R 11 is preferably (1) a halogen, (2) a C1-4 alkyl group, or (3) a cyano group.

[0054] In the present invention, R 12 is preferably (1) a halogen, (2) a C1-4 alkyl group, or (3) a cyano group.

[0055] In the present invention, R 11 or R12 The number of substitutions of each of the above is not limited as long as it is 0 to 5, but is preferably 0 to 3.

[0056] In the present invention, R 2 Preferably, 1 to 5 R 15 and more preferably, 1 to 5 R 15 and more preferably, a 5- to 7-membered heterocyclic ring optionally substituted with 1 to 5 R 15 and particularly preferably a 5- to 7-membered nitrogen-containing saturated heterocyclic ring optionally substituted with 1 to 5 R 15 and optionally substituted pyrrolidine or piperidine.

[0057] In the present invention, R 15 Preferably, (1) 1 to 5 R 18 (1) a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with (2) a C1-8 haloalkyl group or (3) a C1-4 alkoxycarbonyl group, more preferably (1) 1 to 5 R 18 or (2) a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with R 18 and (2) a C1-8 alkyl group optionally substituted with a cyclopropyl group substituted by (1-(trifluoromethyl)cyclopropyl)methyl group, a 3,3,3-trifluoropropyl group, or a 2,2-dimethylpropyl group.

[0058] In the present invention, R 18 is preferably (1) a C1-4 haloalkyl group or (2) a cyano group.

[0059] In the present invention, R 18 The number of substitutions is not limited as long as it is 0 to 5, but is preferably 0 to 3.

[0060] In the present invention, R3 Preferably, (1) 1 to 5 R 20 (2) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 21 or (3)-NR 22 R 23 and more preferably, (1) each of which has 1 to 5 R 20 (2) a 5- to 6-membered carbocyclic ring or indan, optionally substituted with 1 to 5 R 21 or (3) -NR 22 R 23 and more preferably, (1) each of which has 1 to 5 R 20 benzene or indane, or (2)-NR 22 R 23 is.

[0061] In the present invention, R 20 Preferably, (1) 1 to 5 R 27 (1) a C1-4 alkyl group optionally substituted with 1 to 5 R 28 or (4) 1 to 5 R 27-1 and C1-4 alkoxy groups (for example, C1-4 haloalkoxy groups) optionally substituted with.

[0062] In the present invention, R 21 Preferably, (1) 1 to 5 R 27 (1) a C1-4 alkyl group optionally substituted with 1 to 5 R (for example, a C1-4 haloalkyl group or a C1-4 haloalkyl group optionally substituted with 1 to 3 hydroxyl groups, preferably a C1-4 haloalkyl group), (2) a halogen, (3) 1 to 5 R 28 or (4) 1 to 5 R 27-1 and a C1-4 alkoxy group (preferably a C1-4 haloalkoxy group) optionally substituted with.

[0063] In the present invention, R 20 or R 21 The number of substitutions of each of the above is not limited as long as it is 0 to 5, but is preferably 0 to 3.

[0064] In the present invention, R 27 or R 27-1 are preferably (1) halogen, (2) hydroxyl group, (3) carbamoyl group, or (4) carboxyl group, respectively, and more preferably (1) hydroxyl group or (2) carboxyl group.

[0065] In the present invention, R 28 is preferably (1) a halogen, (2) a hydroxyl group, (3) a carbamoyl group, or (4) a carboxyl group, and more preferably (1) a hydroxyl group or (2) a carboxyl group.

[0066] In the present invention, R 27 or R 28 The number of substitutions of each of the above is not limited as long as it is 0 to 5, but is preferably 0 to 3.

[0067] In the present invention, R 22 Preferably, (1) 1 to 5 R 30 or (2) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 31 and more preferably, (1) a 3- to 15-membered heterocyclic ring optionally substituted with 1 to 5 R 30 or (2) a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R 31 and more preferably, (1) a 5- to 6-membered heterocyclic ring optionally substituted with 1 to 5 R 30 benzene, cyclopentane, cyclohexane, or (2) 1 to 5 R 31 and optionally substituted pyridine.

[0068] In the present invention, R 23 is preferably (1) a hydrogen atom, or (2) 1 to 5 R 29(3) a C alkyl group optionally substituted with 1 to 5 R 29-1 or (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2 and more preferably, (1) a hydrogen atom or (2) 1 to 5 R 29 and the like. It is a C1-8 alkyl group (preferably a C1-4 haloalkyl group) optionally substituted with.

[0069] In the present invention, R 29 is preferably (1) halogen, (2) 1 to 5 R 33 (1) a C cycloalkyl group optionally substituted with 1 to 5 R 33 (1) a C3-8 cycloalkyl group optionally substituted with (1), (2) a hydroxyl group, or (3) a carboxyl group.

[0070] In the present invention, R 29-1 is preferably (1) halogen, (2) 1 to 5 R 33 (1) a C cycloalkyl group optionally substituted with 1 to 5 R 33 (1) a C3-8 cycloalkyl group optionally substituted with (1), (2) a hydroxyl group, or (3) a carboxyl group.

[0071] In the present invention, R 29-2 is preferably (1) halogen, (2) 1 to 5 R 33 (1) a C cycloalkyl group optionally substituted with 1 to 5 R 33 (1) a C3-8 cycloalkyl group optionally substituted with (1), (2) a hydroxyl group, or (3) a carboxyl group.

[0072] In the present invention, R 30 Preferably, (1) 1 to 5 R 32 (1) a C1-4 alkyl group optionally substituted with (1-5), (2) a halogen atom, (3) 1 to 5 R 33 (4) a C cycloalkyl group optionally substituted with 1 to 5 R 32-1 (5) a C1-4 alkoxy group optionally substituted with 1 to 5 R 32 (1) a C1-4 alkyl group (preferably a C1-4 haloalkyl group) optionally substituted with (2) a halogen atom; (3) 1 to 5 R 33 or (4) 1 to 5 R 32-1 and a C1-4 alkoxy group (preferably a C1-4 haloalkoxy group) optionally substituted with.

[0073] In the present invention, R 31 Preferably, (1) 1 to 5 R 32 (1) a C1-4 alkyl group optionally substituted with (1-5), (2) a halogen atom, (3) 1 to 5 R 33 (4) a C cycloalkyl group optionally substituted with 1 to 5 R 32-1 (5) a C1-4 alkoxy group optionally substituted with 1 to 5 R 32 (1) a C1-4 alkyl group (preferably a C1-4 haloalkyl group) optionally substituted with (2) a halogen atom; (3) 1 to 5 R 33 or (4) 1 to 5 R 32-1 and a C1-4 alkoxy group (preferably a C1-4 haloalkoxy group) optionally substituted with.

[0074] In the present invention, R 30 or R 31 The number of substitutions of each of the above is not limited as long as it is 0 to 5, but is preferably 0 to 3.

[0075] In the present invention, R32 or R 32-1 is preferably (1) a halogen, (2) a hydroxyl group, (3) a carbamoyl group, (4) a carboxyl group, or (5) a cyano group, and more preferably (1) a halogen, (2) a carbamoyl group, or (3) a carboxyl group.

[0076] In the present invention, R 33 is preferably (1) a halogen, (2) a hydroxyl group, (3) a carbamoyl group, (4) a carboxyl group, or (5) a cyano group, and more preferably (1) a halogen, (2) a carbamoyl group, or (3) a carboxyl group.

[0077] In the present invention, R 4 is preferably (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, or (5) a C1-4 haloalkoxy group.

[0078] In the present invention, R 5 is preferably (1) a C1-4 alkyl group, (2) a C1-4 haloalkyl group, or (3) a hydroxyl group.

[0079] In the present invention, R 6 is preferably (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, or (5) a C1-4 haloalkoxy group, and more preferably (1) a halogen or (2) a C1-4 alkyl group.

[0080] In the present invention, X 1 is preferably CH or CR 6 is.

[0081] In the present invention, X 2 is preferably CH or CR 6 is.

[0082] In the present invention, X 3 is preferably CH or CR6 is.

[0083] In the present invention, Y 1 is preferably a nitrogen atom.

[0084] In the present invention, Y 2 is preferably a nitrogen atom.

[0085] In the present invention, Y 3 Preferably, CR 10 is.

[0086] In the present invention, R 7 is preferably a hydrogen atom.

[0087] In the present invention, R 8 is preferably a hydrogen atom.

[0088] In the present invention, R 9 is preferably a hydrogen atom.

[0089] In the present invention, R 10 is preferably (1) a hydrogen atom, (2) a C1-4 alkyl group, (3) an amino group, (4) a carboxyl group, (5) a carbamoyl group, (6) a (C1-4 alkyl)aminocarbonyl group, or (7) -CONHR 39 or (8) a cyano group, and more preferably (1) a hydrogen atom or (2) a C1-4 alkyl group.

[0090] In the present invention, r is preferably 0 or 1.

[0091] In the present invention, s is preferably 0 or 1.

[0092] In the present invention, the compound represented by general formula (I) is preferably a compound represented by general formula (I-1)

[0093] [ka]

[0094] (wherein t represents an integer of 0 to 3, and other symbols have the same meanings as above), and more preferably, a compound represented by the general formula (I-1-1):

[0095] [ka]

[0096] (In the formula, R 1-1 is 1 to 5 R 11 ring 1 represents a 5- to 7-membered nitrogen-containing saturated heterocycle; R 3-1 (1) 1 to 5 R 20 (2) a 5- to 6-membered carbocyclic ring or indan, optionally substituted with 1 to 5 R 21 or (3) -NR 22 R 23 represents R 15-1 is 1 to 5 R 18 represents a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with, or a C1-8 haloalkyl group, u represents an integer of 0 to 2, and other symbols have the same meanings as above), and more preferably a compound represented by the general formula (I-1-1-1):

[0097] [ka]

[0098] (Wherein, ring 2 is (1) each of 1 to 5 R 20 (2) a 5- to 6-membered carbocyclic ring or indane, optionally substituted with 1 to 5 R 21 and the other symbols have the same meanings as above.), a compound represented by the general formula (I-1-1-2):

[0099] [ka]

[0100] (wherein ring 3 is a group having 1 to 5 R 30 a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R 31 represents a 5- to 6-membered heterocycle optionally substituted by 23-1 is (1) a hydrogen atom, (2) 1 to 5 R 29 (3) a C alkyl group optionally substituted with 1 to 5 R 29-1 or (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2 a C2-4 alkynyl group (preferably, (1) a hydrogen atom, or (2) 1 to 5 R 29 and the other symbols have the same meanings as above, or a compound represented by the general formula (I-1-1-3):

[0101] [ka]

[0102] (wherein all symbols have the same meanings as above).

[0103] In the present invention, the compound represented by general formula (I) includes a compound represented by general formula (I-1-1-1-1):

[0104] [ka]

[0105] (wherein ring2-1 is a group consisting of 1 to 5 R 20 represents a 5- or 6-membered carbocyclic ring optionally substituted with, or indan, v1 represents an integer of 0 to 5, and other symbols have the same meanings as defined above.) are also preferred.

[0106] In the present invention, the compound represented by general formula (I) includes a compound represented by general formula (I-1-1-1-2):

[0107] [ka]

[0108] (wherein ring 2-2 is 1 to 5 R 21 represents a 5- or 6-membered heterocycle optionally substituted by, v2 represents an integer of 0 to 5, and the other symbols have the same meanings as defined above. ) The other symbols have the same meanings as defined above. ) is also preferred.

[0109] In the present invention, the compound represented by general formula (I) includes a compound represented by general formula (I-1-1-2-1):

[0110] [ka]

[0111] (wherein ring3-1 is 1 to 5 R 30 represents a 5- or 6-membered carbocyclic ring optionally substituted with, w1 represents an integer of 0 to 5, and other symbols have the same meanings as defined above. ) is also preferred.

[0112] In the present invention, the compound represented by general formula (I) includes a compound represented by general formula (I-1-1-2-2):

[0113] [ka]

[0114] (wherein ring 3-2 is 1 to 5 R 31 represents a 5- or 6-membered heterocycle optionally substituted with, w2 represents an integer of 0 to 5, and other symbols have the same meanings as defined above. ) is also preferred.

[0115] In the present invention, the compound is preferably (1) 2-methyl-2-propanyl (3S)-3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-pyrrolidinecarboxylate, (2) 1-(3-{7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)cyclopropanecarboxylic acid, (3) 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-{[4-(difluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one, (4) 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, (5) 9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7-(6-{[9-(2-fluoro-4-methylbenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-6-methyl-2-{[4-(trifluoromethoxy)phenyl]amino}-7,9-dihydro-8H-purin-8-one, (6) 4-[(7-{[5-(9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, (7) 3-fluoro-4-({7-[(5-{2-[(3-fluorophenyl)amino]-6-methyl-8-oxo-9-(1-{[1-(trifluoromethyl)cyclopropyl]methyl}-4-piperidinyl)-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile, (8) 4-[(7-{[5-(2-{[2-chloro-4-(trifluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, (9) 2-(3-{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)-2-methylpropanoic acid, (10) 4-({7-[(5-{9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-2-[2-methyl-4-(trifluoromethoxy)phenyl]-8-oxo-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)-3-fluorobenzonitrile, (11) 1-{[{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}(cyclohexyl)amino]methyl}cyclobutanecarboxylic acid, or (12) 7-(6-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, or a salt thereof.

[0116] In the present invention, the compound represented by general formula (I) is preferably 2-methyl-2-propanyl (3S)-3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-pyrrolidinecarboxylate or a salt thereof.

[0117] In the present invention, the compound represented by general formula (I) is preferably 1-(3-{7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)cyclopropanecarboxylic acid or a salt thereof.

[0118] In the present invention, the compound represented by general formula (I) is preferably 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-{[4-(difluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one, or a salt thereof.

[0119] In the present invention, the compound represented by general formula (I) is preferably 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, or a salt thereof.

[0120] In the present invention, the compound represented by general formula (I) is preferably 9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7-(6-{[9-(2-fluoro-4-methylbenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-6-methyl-2-{[4-(trifluoromethoxy)phenyl]amino}-7,9-dihydro-8H-purin-8-one, or a salt thereof.

[0121] In the present invention, the compound represented by general formula (I) is preferably 4-[(7-{[5-(9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, or a salt thereof.

[0122] In the present invention, the compound represented by general formula (I) is preferably 3-fluoro-4-({7-[(5-{2-[(3-fluorophenyl)amino]-6-methyl-8-oxo-9-(1-{[1-(trifluoromethyl)cyclopropyl]methyl}-4-piperidinyl)-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile, or a salt thereof.

[0123] In the present invention, the compound represented by general formula (I) is preferably 4-[(7-{[5-(2-{[2-chloro-4-(trifluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, or a salt thereof.

[0124] In the present invention, the compound represented by general formula (I) is preferably 2-(3-{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)-2-methylpropanoic acid or a salt thereof.

[0125] In the present invention, the compound represented by general formula (I) is preferably 4-({7-[(5-{9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-2-[2-methyl-4-(trifluoromethoxy)phenyl]-8-oxo-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)-3-fluorobenzonitrile, or a salt thereof.

[0126] In the present invention, the compound represented by general formula (I) is preferably 1-{[{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}(cyclohexyl)amino]methyl}cyclobutanecarboxylic acid, or a salt thereof.

[0127] In the present invention, the compound represented by general formula (I) is preferably 7-(6-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, or a salt thereof. [Isomers] Unless otherwise specified, the present invention encompasses all isomers. For example, alkyl groups include straight-chain and branched-chain isomers. Furthermore, the present invention encompasses geometric isomers (E-, Z-, cis-, and trans-isomers) in double bonds, rings, and fused rings; optical isomers (R-, S-, α-, β-configurations, enantiomers, and diastereomers) due to the presence of asymmetric carbon atoms; optically active isomers (D-, L-, d-, and l-isomers) with optical rotation; polar isomers (highly polar and less polar) obtained by chromatographic separation; equilibrium compounds; rotational isomers; mixtures of these in any proportion; and racemic mixtures. The present invention also encompasses all isomers resulting from tautomers.

[0128] Furthermore, the optical isomer in the present invention need not necessarily be 100% pure, but may contain less than 50% of other optical isomers.

[0129] In the present invention, unless otherwise specified, the symbols

[0130] [ka]

[0131] indicates bonding to the other side of the paper (i.e., α-configuration),

[0132] [ka]

[0133] indicates that the molecule is bonded to the front side of the paper (i.e., the β configuration),

[0134] [ka]

[0135] represents an α-configuration, a β-configuration, or a mixture thereof in any ratio. [N-oxide] The compound represented by general formula (I) can be converted into an N-oxide by a known method. The N-oxide refers to a compound in which the nitrogen atom of the compound represented by general formula (I) is oxidized. These N-oxides may also be in the form of prodrugs, pharmaceutically acceptable salts, or solvates thereof, as described in the following sections [Prodrugs], [Salts], and [Solvates]. [Prodrug] The compound represented by general formula (I) or its N-oxide can also be made into a prodrug by a known method. Such a prodrug refers to a compound that is converted into, for example, the compound represented by general formula (I) or its N-oxide by a reaction with an enzyme, gastric acid, or the like in vivo. Note that the prodrug of the compound represented by general formula (I) or its N-oxide may be converted into the corresponding compound represented by general formula (I) or its N-oxide under physiological conditions as described in "Drug Development," Vol. 7, "Molecular Design," pp. 163-198, Hirokawa Shoten, 1990.

[0136] Other prodrugs of the compound represented by general formula (I) or its N-oxide derivative include, for example, when the compound represented by general formula (I) has an amino group, compounds in which the amino group has been acylated, alkylated or phosphorylated (for example, compounds in which the amino group of the compound represented by general formula (I) has been eicosanoylated, alanylated, pentylaminocarbonylated, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxycarbonylated, tetrahydrofuranylated, pyrrolidylmethylated, pivaloyloxymethylated, acetoxymethylated or tert-butylated, etc.), and when the compound represented by general formula (I) has a hydroxyl group, compounds in which the hydroxyl group has been acylated, alkylated, phosphorylated or borated (for example, compounds in which the hydroxyl group of the compound represented by general formula (I) has been acetylated, paclitaxelated or tert-butylated). When the compound represented by general formula (I) has a carboxy group, examples thereof include compounds in which the carboxy group is esterified or amidated (for example, compounds in which the carboxy group of the compound represented by general formula (I) is ethyl esterified, phenyl esterified, carboxymethyl esterified, dimethylaminomethyl esterified, pivaloyloxymethyl esterified, 1-{(ethoxycarbonyl)oxy}ethyl esterified, phthalidyl esterified, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methyl esterified, 1-{[(cyclohexyloxy)carbonyl]oxy}ethyl esterified, or methylamidized). These compounds can be produced by methods known per se. The compound represented by general formula (I) or a prodrug of its N-oxide may be in the form of a pharmaceutically acceptable salt or solvate thereof, as described in the following sections [Salts] and [Solvates]. [salt] The compound represented by general formula (I), its N-oxide or a prodrug thereof can be converted into a corresponding pharmaceutically acceptable salt by a known method. Examples of the pharmaceutically acceptable salt include alkali metal salts (e.g., lithium salt, sodium salt, potassium salt, etc.), alkaline earth metal salts (e.g., calcium salt, magnesium salt, barium salt, etc.), ammonium salts, organic amine salts (e.g., aliphatic amine salts (e.g., methylamine salt, dimethylamine salt, cyclopentylamine salt, trimethylamine salt, triethylamine salt, dicyclohexylamine salt, monoethanolamine salt, diethanolamine salt, triethanolamine salt, procaine salt, meglumine salt, diethanolamine salt, tris(hydroxymethyl)aminomethane salt, ethylenediamine salt, etc.), aralkylamine salts (e.g., benzylamine salt, phenethylamine salt, N,N-dibenzylethylenediamine salt, benethamine salt, etc.), heterocyclic aromatic amine salts (e.g., piperidine salt, pyridine salt, picoline salt, quinolinol salt, etc.), and the like. Examples of suitable pharmaceutically acceptable salts include amine salts and isoquinoline salts, quaternary ammonium salts (e.g., tetramethylammonium salts, tetraethylammonium salts, benzyltrimethylammonium salts, benzyltriethylammonium salts, benzyltributylammonium salts, methyltrioctylammonium salts, and tetrabutylammonium salts), basic amino acid salts (e.g., arginine salts, lysine salts, and N-methyl-D-glucamine salts), and acid addition salts (e.g., inorganic acid salts (e.g., hydrochloride, hydrobromide, hydroiodide, sulfate, phosphate, and nitrate), and organic acid salts (e.g., acetate, trifluoroacetate, lactate, tartrate, oxalate, fumarate, maleate, benzoate, citrate, methanesulfonate, ethanesulfonate, benzenesulfonate, toluenesulfonate, isethionate, glucuronate, and gluconate). Pharmaceutically acceptable salts are preferably water-soluble.

[0137] The salt also includes quaternary ammonium salts. Quaternary ammonium salts are salts in which the nitrogen atom of the compound represented by general formula (I) is R 0 represents a quaternized group, where R0 The group represents, for example, a C1-8 alkyl group which may be substituted by a phenyl group. [Solvate] The compound represented by general formula (I), its N-oxide, their prodrug or their pharmaceutically acceptable salt may exist in a non-solvated form or in a solvated form with a pharmaceutically acceptable solvent such as water, ethanol, etc. The solvate is preferably a hydrate.

[0138] The compound represented by general formula (I), its N-oxide, a prodrug thereof, or a pharmaceutically acceptable salt thereof can also be converted into a solvate by a known method. Preferably, the solvate is low-toxicity and water-soluble. Suitable solvates include solvates with water or alcoholic solvents (e.g., ethanol, etc.). Hydrates may take the form of polyhydrates such as monohydrates to pentahydrates, or low-hydrate forms such as hemihydrates. Hydrate forms of the compound of the present invention include, for example, monohydrates, dihydrates, trihydrates, and di- to trihydrates. These hydrate forms also include clathrate hydrates. These hydrates can be obtained, for example, by precipitating the compound represented by general formula (I), its N-oxide, a prodrug thereof, or a pharmaceutically acceptable salt thereof from an aqueous organic solvent. [Cocrystal] The compound represented by formula (I), its N-oxide, prodrug, pharmaceutically acceptable salt, or solvate thereof can form a cocrystal with a suitable cocrystal former. The cocrystal is preferably a pharmaceutically acceptable cocrystal formed with a pharmaceutically acceptable cocrystal former. A cocrystal is defined as a crystal formed by two or more different molecules through intermolecular interactions other than ionic bonding. A cocrystal may also be a complex of a neutral molecule and a salt. Cocrystals can be prepared by known methods, such as melt crystallization, recrystallization from a solvent, or physical grinding of the components together. Suitable cocrystal formers include those described in WO 2006 / 007448, such as 4-aminobenzoic acid, 4-aminopyridine, adenine, alanine, and acetylsalicylic acid. [Radioisotope] The compounds represented by the general formula (I), their N-oxides, their prodrugs, their pharmaceutically acceptable salts or their solvates may contain isotopes (e.g., 2 H, 3 H, 11 C. 13 C. 14 C. 13 N, 15 N, 15 O. 17 O. 18 O. 35 S, 18 F, 36 Cl, 123 I, 125 For example, R in general formula (I) may be labeled with 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 and R 10 and compounds in which all or part of the hydrogen atoms constituting one or more groups of the formula (I) are substituted with deuterium atoms or tritium atoms.

[0139] All references to the compounds of the present invention include a compound of general formula (I), a pharmaceutically acceptable salt thereof, an N-oxide thereof, a solvate (e.g., hydrate) thereof, or a co-crystal thereof, or an N-oxide of a pharmaceutically acceptable salt of a compound of general formula (I), a solvate (e.g., hydrate) thereof, or a co-crystal thereof. [Method of producing the compound of the present invention] The compound of the present invention can be produced by appropriately modifying and combining known methods, for example, the method described in Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999), the methods described below, or the methods described in the Examples.

[0140] Among the compounds represented by general formula (I), R 3 However, 1 to 5 R 20 benzene optionally substituted with X 1 , X 2 , and X 3 are each independently CH or CR 6 Compounds of general formula (IA)

[0141] [ka]

[0142] (wherein v represents an integer of 0 to 3, and the other symbols have the same meanings as above) can be produced by the method shown in the following reaction scheme 1. In reaction scheme 1, E 1 , E 2 and E 3 each independently represents a leaving group (e.g., a fluorine atom, a bromine atom, a chlorine atom, an iodine atom, a trifluoromethanesulfonate ester, a p-toluenesulfonate ester, etc.), P c represents a protecting group for a carboxyl group, and R BOrepresents a boron-containing group (e.g., -B(OH)2, -B(OCH3)2, 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl), 3-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl), potassium trifluoroborate, etc.), and the other symbols have the same meanings as above.

[0143] [ka]

[0144] The compound represented by general formula (IV) can be produced by subjecting a compound represented by general formula (II) and a compound represented by general formula (III) to an amino group introduction reaction.

[0145] This reaction for introducing an amino group is known and can be carried out, for example, in an organic solvent (dichloromethane, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, etc.) or without a solvent, in the presence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, etc.) at a temperature of room temperature to 180°C.

[0146] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0147] The compound represented by general formula (VI) can be produced by subjecting a compound represented by general formula (IV) and a compound represented by general formula (V) to a coupling reaction.

[0148] This coupling reaction is known and can be carried out, for example, in an organic solvent (benzene, toluene, dimethylformamide, dimethylacetamide, 1,4-dioxane, tetrahydrofuran, methanol, acetonitrile, dimethoxyethane, acetone, or a mixture thereof, etc.), using a base (sodium ethylate, sodium butoxide, sodium hydroxide, potassium hydroxide, triethylamine, sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, thallium carbonate, tripotassium phosphate, cesium fluoride, barium hydroxide, tetrabutylammonium fluoride, lithium bis(trimethylsilyl)amide (LHMDS), etc.) or a mixture thereof, a phosphine ligand ((9,9)-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (Xanthos), dicyclohexyl methyl ester (DMT ... The reaction is carried out at temperatures between room temperature and 150°C in the presence of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2), palladium acetate (Pd(OAc)2), palladium black, 1,1'-bis(diphenylphosphinoferrocene)dichloropalladium (PdCl2(dppf)2), diallylpalladium dichloride (PdCl2(allyl)2), phenylbis(triphenylphosphine)palladium iodide (PpdI(PPh3)2), (1E,4E)-1,5-diphenyl-1,4-pentadiene-3-one-palladium (Pd2(dba)3)), etc.

[0149] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0150] The compound represented by the general formula (VII) can be produced by subjecting the compound represented by the general formula (VI) to a cyclization reaction.

[0151] This cyclization reaction is known and is carried out, for example, in an organic solvent (tetrahydrofuran, dimethylformamide, dimethylacetamide, dichloromethane, etc.) using a reagent (1,1'-carbonyldiimidazole (CDI), triphosgene, 2,2,2-trichloroethyl carbonchloridate, etc.) in the presence or absence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, etc.) at a temperature ranging from ice-cooling to reflux.

[0152] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0153] The compound represented by the general formula (VIII) can be produced by subjecting the compound represented by the general formula (VII) to a deprotection reaction of the protecting group of the carboxyl group.

[0154] Examples of the protecting group for a carboxyl group include a methyl group, an ethyl group, an allyl group, a t-butyl group, a trichloroethyl group, a benzyl (Bn) group, a phenacyl group, a p-methoxybenzyl group, a trityl group, a 2-chlorotrityl group, or a solid support having any of these structures bound thereto.

[0155] The carboxyl-protecting group is not particularly limited as long as it can be easily and selectively removed, in addition to the above-mentioned groups. For example, those described in PGM Wuts, T.W. Greene, Green's Protective Groups in Organic Synthesis, Wiley, Fourth Edition, New York, 2007, can be used.

[0156] The deprotection reaction of the carboxyl protecting group is well known, for example, (1) Alkaline hydrolysis (2) Deprotection reaction under acidic conditions, (3) deprotection by hydrogenolysis, (4) deprotection reaction of the silyl group, (5) Metal-mediated deprotection reaction, (6) Deprotection reactions using metal complexes, etc.

[0157] To explain these methods in detail, (1) The deprotection reaction by alkaline hydrolysis is carried out, for example, in an organic solvent (e.g., methanol, tetrahydrofuran, 1,4-dioxane) using an alkali metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide), an alkali metal silanol salt (e.g., potassium trimethylsilanolate), an alkaline earth metal hydroxide (e.g., barium hydroxide, calcium hydroxide), or a carbonate (e.g., sodium carbonate, potassium carbonate), or an aqueous solution thereof, or a mixture thereof, at a temperature of 0 to 80°C.

[0158] (2) The deprotection reaction under acidic conditions is carried out, for example, in an organic solvent (dichloromethane, chloroform, 1,4-dioxane, ethyl acetate, anisole, etc.), in an organic acid (acetic acid, trifluoroacetic acid, methanesulfonic acid, p-tosylic acid, etc.), an inorganic acid (hydrochloric acid, sulfuric acid, etc.), or a mixture thereof (hydrogen bromide / acetic acid, etc.), in the presence or absence of 2,2,2-trifluoroethanol, at a temperature of 0 to 100°C.

[0159] (3) The deprotection reaction by hydrogenolysis is carried out, for example, in an organic solvent (tetrahydrofuran, 1,4-dioxane, dimethoxyethane, diethyl ether, methanol, ethanol, benzene, toluene, acetone, methyl ethyl ketone, acetonitrile, dimethylformamide, etc.), water, ethyl acetate, acetic acid, or a mixed solvent of two or more thereof, in the presence of a catalyst (palladium-carbon, palladium black, palladium hydroxide-carbon, platinum oxide, Raney nickel, etc.), under normal or elevated pressure in a hydrogen atmosphere or in the presence of ammonium formate, at a temperature of 0 to 200°C.

[0160] (4) The deprotection reaction of the silyl group is carried out, for example, in a water-miscible organic solvent (tetrahydrofuran, acetonitrile, etc.) using tetrabutylammonium fluoride at a temperature of 0 to 40°C.

[0161] (5) The deprotection reaction using a metal is carried out, for example, in an acidic solvent (acetic acid, a buffer solution of pH 4.2 to 7.2, or a mixture of such a solution with an organic solvent such as tetrahydrofuran) in the presence of zinc powder, with ultrasonication if necessary, at a temperature of 0 to 40°C.

[0162] (6) The deprotection reaction using a metal complex is carried out in, for example, an organic solvent (dichloromethane, dimethylformamide, tetrahydrofuran, ethyl acetate, acetonitrile, 1,4-dioxane, ethanol, etc.), water, or a mixture thereof, in the presence of a trapping reagent (tributyltin hydride, triethylsilane, dimedone, morpholine, diethylamine, pyrrolidine, etc.), an organic acid (acetic acid, formic acid, 2-ethylhexanoic acid, etc.) and / or an organic acid salt (sodium 2-ethylhexanoate, potassium 2-ethylhexanoate, etc.), in the presence or absence of a phosphine reagent (triphenylphosphine, etc.), using a metal complex (tetrakis(triphenylphosphine)palladium (Pd(PPh), bis(triphenylphosphine)palladium dichloride (PdCl(PPh)), palladium acetate (Pd(OAc)), tris(triphenylphosphine)rhodium chloride (RhCl(PPh)), etc.) at a temperature of 0 to 40°C.

[0163] In addition to the above, the deprotection reaction can also be carried out by the method described in, for example, "Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999)" and "PGM Wuts, T.W. Greene, Green's Protective Groups in Organic Synthesis, Wiley, Fourth Edition, New York, 2007."

[0164] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0165] The compound represented by general formula (X) can be produced by subjecting a compound represented by general formula (VIII) and a compound represented by general formula (IX) to an amidation reaction.

[0166] This amidation reaction is known and can be carried out, for example, by (1) A method using an acid halide (2) A method using a mixed acid anhydride, (3) A method using a condensing agent.

[0167] To explain these methods in detail, (1) The method using an acid halide is carried out, for example, by reacting a carboxylic acid with an acid halide agent (oxalyl chloride, thionyl chloride, etc.) in an organic solvent (chloroform, dichloromethane, diethyl ether, tetrahydrofuran, etc.) or without a solvent at −20° C. to reflux temperature, and then reacting the resulting acid halide with an amine in the presence of a base (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, diisopropylethylamine, etc.) in an organic solvent (chloroform, dichloromethane, diethyl ether, tetrahydrofuran, etc.) at a temperature of 0 to 40° C. Alternatively, the resulting acid halide can be reacted with an amine in an organic solvent (1,4-dioxane, tetrahydrofuran, etc.) using an aqueous alkali solution (sodium bicarbonate solution, sodium hydroxide solution, etc.) at 0 to 40° C.

[0168] (2) The method using a mixed acid anhydride is carried out by, for example, reacting a carboxylic acid with an acid halide (pivaloyl chloride, tosyl chloride, mesyl chloride, etc.) or an acid derivative (ethyl chloroformate, isobutyl chloroformate, etc.) in the presence of a base (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, diisopropylethylamine, etc.) in an organic solvent (chloroform, dichloromethane, diethyl ether, tetrahydrofuran, etc.) or without a solvent at 0 to 40°C, and then reacting the resulting mixed acid anhydride with an amine in an organic solvent (chloroform, dichloromethane, diethyl ether, tetrahydrofuran, etc.) at 0 to 40°C.

[0169] (3) The method using a condensing agent involves, for example, reacting a carboxylic acid and an amine in an organic solvent (chloroform, dichloromethane, dimethylformamide, diethyl ether, tetrahydrofuran, etc.) or without a solvent, in the presence or absence of a base (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, N,N-diisopropylethylamine, etc.), with a condensing agent (1,3-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide (EDC), 1,1'-carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide, 1-propylphosphonic acid cyclic anhydride (1-propanephosphonic acid cyclic anhydride, PPA), 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium). The reaction is carried out using chloro(dimethylamino)-N,N-dimethyl(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methaniminium hexafluorophosphate (DMTMM), (dimethylamino)-N,N-dimethyl(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methaniminium hexafluorophosphate (HATU), chloro(dimethylamino)-N,N-dimethylmethaniminium hexafluorophosphate (TCFH), etc., in the presence or absence of 1-hydroxybenztriazole (HOBt) at 0 to 40°C.

[0170] It is desirable that the reactions (1), (2) and (3) are all carried out under an inert gas (argon, nitrogen, etc.) atmosphere and under anhydrous conditions.

[0171] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0172] The compound represented by general formula (IA) can be produced by subjecting a compound represented by general formula (X) and a compound represented by general formula (XI) to a coupling reaction.

[0173] This coupling reaction is known, and can be carried out, for example, in an organic solvent (benzene, toluene, dimethylformamide, 1,4-dioxane, tetrahydrofuran, methanol, acetonitrile, dimethoxyethane, acetone, 1-methyl-2-pyrrolidinone, a mixed solvent thereof, or the like), with a base (sodium ethylate, sodium hydroxide, potassium hydroxide, triethylamine, sodium carbonate, sodium hydrogencarbonate, potassium carbonate, cesium carbonate, thallium carbonate, tripotassium phosphate, cesium fluoride, barium hydroxide, tetrabutylammonium fluoride, or the like) or an aqueous solution thereof, or a mixture thereof, and with a catalyst (tetrakis(triphenylphosphine)).

[0039] The reaction can be carried out at room temperature to 150°C in the presence of bis(triphenylphosphine)palladium (Pd(PPh3)4), bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2), palladium acetate (Pd(OAc)2), palladium black, 1,1'-bis(diphenylphosphinoferrocene)dichloropalladium (PdCl2(dppf)2), diallylpalladium dichloride (PdCl2(allyl)2), phenylbis(triphenylphosphine)palladium iodide (PhPdI(PPh3)2), (1E,4E)-1,5-diphenyl-1,4-pentadiene-3-one-palladium (Pd2(dba)3), etc.

[0174] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0175] Among the compounds represented by general formula (IA), R 2 is a 5- to 7-membered nitrogen-containing saturated heterocycle, and R 15 However, 1 to 5 R 18 a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group, or a C1-8 haloalkyl group, i.e., a compound represented by the general formula (IA-1):

[0176] [ka]

[0177] (wherein ring 1 represents a 5- to 7-membered nitrogen-containing saturated heterocycle, R 15-1 is 1 to 5 R 18 represents a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with, or a C1-8 haloalkyl group, u represents an integer of 0 to 2, and other symbols have the same meanings as above.) can be produced by the methods shown in the following reaction schemes 1-1a and 1-1b. In reaction schemes 1-1a and 1-1b, R 15-2 is a hydrogen atom or 1 to 5 R 18 represents a C1-7 alkyl group optionally substituted by a C3-6 cycloalkyl group optionally substituted by 4 represents a leaving group (e.g., fluorine atom, bromine atom, chlorine atom, iodine atom, trifluoromethanesulfonate ester, p-toluenesulfonate ester, etc.), P N-1 represents a protecting group for an amino group, and the other symbols have the same meanings as above.

[0178] [ka]

[0179] [ka]

[0180] The compound represented by general formula (IV-1) can be produced by subjecting a compound represented by general formula (II) and a compound represented by general formula (III-1) to an amino group introduction reaction.

[0181] The reaction for introducing this amino group is the same as the reaction for producing the compound represented by the above-mentioned general formula (IV).

[0182] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0183] The compound represented by general formula (VI-1) can be produced by subjecting a compound represented by general formula (IV-1) and a compound represented by general formula (V) to a coupling reaction.

[0184] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VI).

[0185] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0186] The compound represented by the general formula (VII-1) can be produced by subjecting the compound represented by the general formula (VI-1) to a cyclization reaction.

[0187] This cyclization reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VII).

[0188] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0189] The compound represented by the general formula (VIII-1) can be produced by subjecting the compound represented by the general formula (VII-1) to a deprotection reaction of the protecting group of the carboxyl group.

[0190] The deprotection reaction of the carboxyl protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (VIII).

[0191] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0192] The compound represented by general formula (X-1) can be produced by subjecting a compound represented by general formula (VIII-1) and a compound represented by general formula (IX) to an amidation reaction.

[0193] This amidation reaction is the same as the reaction used in producing the compound represented by the above-mentioned general formula (X).

[0194] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0195] The compound represented by the general formula (XVI-1) can be produced by subjecting the compound represented by the general formula (X-1) to a deprotection reaction of the amino-protecting group.

[0196] Examples of the amino-protecting group include a benzyloxycarbonyl group, a tert-butoxycarbonyl group, an allyloxycarbonyl (Alloc) group, a 1-methyl-1-(4-biphenyl)ethoxycarbonyl (Bpoc) group, a trifluoroacetyl group, a 9-fluorenylmethoxycarbonyl group, a benzyl (Bn) group, a 4-methoxybenzyl group, a benzyloxymethyl (BOM) group, and a 2-(trimethylsilyl)ethoxymethyl (SEM) group.

[0197] The amino-protecting group is not particularly limited as long as it can be easily and selectively removed, in addition to the above-mentioned groups. For example, those described in PGM Wuts, T.W. Greene, Green's Protective Groups in Organic Synthesis, Wiley, Fourth Edition, New York, 2007, can be used.

[0198] The deprotection reaction of the amino protecting group is known, for example, (1) Alkaline hydrolysis (2) Deprotection reaction under acidic conditions, (3) deprotection by hydrogenolysis, (4) deprotection reaction of the silyl group, (5) Metal-mediated deprotection reaction, (6) Deprotection reactions using metal complexes.

[0199] To explain these methods in detail, (1) The deprotection reaction by alkaline hydrolysis is carried out, for example, in an organic solvent (e.g., methanol, tetrahydrofuran, 1,4-dioxane) using an alkali metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide), an alkaline earth metal hydroxide (e.g., barium hydroxide, calcium hydroxide), or a carbonate (e.g., sodium carbonate, potassium carbonate), or an aqueous solution thereof, or a mixture thereof, at a temperature of 0 to 40°C.

[0200] (2) The deprotection reaction under acidic conditions is carried out, for example, in an organic solvent (dichloromethane, chloroform, 1,4-dioxane, ethyl acetate, anisole, etc.), an organic acid (acetic acid, trifluoroacetic acid, methanesulfonic acid, p-tosylic acid, etc.), an inorganic acid (hydrochloric acid, sulfuric acid, etc.), or a mixture thereof (hydrogen bromide / acetic acid, etc.) at a temperature of 0 to 100°C.

[0201] (3) The deprotection reaction by hydrogenolysis is carried out, for example, in an organic solvent (tetrahydrofuran, 1,4-dioxane, dimethoxyethane, diethyl ether, methanol, ethanol, benzene, toluene, acetone, methyl ethyl ketone, acetonitrile, dimethylformamide, water, ethyl acetate, acetic acid, etc., or a mixed solvent thereof) in the presence of a catalyst (palladium-carbon, palladium black, palladium hydroxide, platinum oxide, Raney nickel, etc.) under a hydrogen atmosphere at normal or elevated pressure or in the presence of ammonium formate at a temperature of 0 to 200°C.

[0202] (4) The deprotection reaction of the silyl group is carried out, for example, in a water-miscible organic solvent (tetrahydrofuran, acetonitrile, etc.) using tetrabutylammonium fluoride or the like at a temperature of 0 to 40°C.

[0203] (5) The deprotection reaction using a metal is carried out, for example, in an acidic solvent (acetic acid, a buffer solution of pH 4.2 to 7.2, or a mixed solvent of such a solution with an organic solvent such as tetrahydrofuran) in the presence of zinc powder, with ultrasonication if necessary, at a temperature of 0 to 40°C.

[0204] (6) The deprotection reaction using a metal complex is carried out in, for example, an organic solvent (dichloromethane, dimethylformamide, tetrahydrofuran, ethyl acetate, acetonitrile, 1,4-dioxane, ethanol, etc.), water, or a mixture thereof, in the presence of a trapping reagent (tributyltin hydride, triethylsilane, dimedone, morpholine, diethylamine, pyrrolidine, etc.), an organic acid (acetic acid, formic acid, 2-ethylhexanoic acid, etc.) and / or an organic acid salt (sodium 2-ethylhexanoate, potassium 2-ethylhexanoate, etc.), in the presence or absence of a phosphine reagent (triphenylphosphine, etc.), using a metal complex (tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2), palladium acetate (Pd(OAc)2), tris(triphenylphosphine)rhodium chloride (RhCl(PPh3)3), etc.) at a temperature of 0 to 40°C.

[0205] In addition to the above, the deprotection reaction can also be carried out by the method described in, for example, "Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 2nd Edition (Richard C. Larock, John Wiley & Sons Inc, 1999)" and "PGM Wuts, T.W. Greene, Green's Protective Groups in Organic Synthesis, Wiley, Fourth Edition, New York, 2007."

[0206] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0207] The compound represented by general formula (XIX-1) can be produced by alkylating a compound represented by general formula (XVI-1) with a compound represented by general formula (XVII-1) or a compound represented by general formula (XVIII-1).

[0208] This alkylation reaction is known. When a compound represented by general formula (XVII-1) is used, the reaction is carried out, for example, in an organic solvent (dimethylformamide, dimethylacetamide, dimethyl sulfoxide, chloroform, dichloromethane, diethyl ether, tetrahydrofuran, methyl t-butyl ether, etc.) in the presence of an organic base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, etc.), an alkali metal hydroxide (sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), an alkaline earth metal hydroxide (barium hydroxide, calcium hydroxide, etc.) or carbonate (sodium carbonate, potassium carbonate, etc.), or an aqueous solution thereof, or a mixture thereof, in the presence or absence of an alkali metal halide salt (potassium iodide, sodium iodide, etc.), at 0 to 100°C.

[0209] When the compound represented by the general formula (XVIII-1) is used, the target product can be obtained by a reductive amination reaction.

[0210] This reductive amination reaction is known, and the imine produced in the reaction may be isolated and then reduced, or the imine may be produced in the reaction system and reduced without isolation (in one pot). This imine-producing reaction is known, and can be carried out, for example, in an organic solvent (e.g., methanol, ethanol, dichloromethane, chloroform, dichloroethane, benzene, toluene, or a mixture thereof) in the presence or absence of a dehydrating agent (e.g., anhydrous magnesium sulfate, molecular sieves (trade name)), and in the presence or absence of an acid (e.g., hydrochloric acid, acetic acid), at a temperature of 20°C to reflux. The reduction reaction of imines is also known. For example, the reduction reaction can be carried out in an organic solvent (e.g., tetrahydrofuran, diethyl ether, dichloroethane, dichloromethane, dimethylformamide, acetic acid, methanol, ethanol, or a mixture thereof) in the presence of a reducing agent (e.g., sodium triacetoxyborohydride, sodium cyanoborohydride, sodium borohydride, zinc borohydride, diisobutylaluminum hydride, 2-picoline borane complex, or the like) at a temperature of 0 to 40°C; or in a solvent (e.g., tetrahydrofuran, 1,4-dioxane, dimethoxyethane, diethyl ether, methanol, ethanol, benzene, toluene, acetonitrile, dimethylformamide, water, ethyl acetate, acetic acid, or a mixed solvent thereof) in the presence of a catalyst (e.g., palladium-carbon, palladium black, palladium hydroxide, platinum oxide, Raney nickel, or the like) under a hydrogen atmosphere at atmospheric pressure or elevated pressure at a temperature of 0 to 200°C. Furthermore, reductive amination reactions carried out without isolating the imine are known, and can be carried out, for example, in an organic solvent (tetrahydrofuran, dichloroethane, dichloromethane, dimethylformamide, acetic acid, a mixture thereof, or the like) in the presence of a reducing agent (sodium triacetoxyborohydride, sodium cyanoborohydride, sodium borohydride, 2-picoline borane complex, or the like) at a temperature of 0 to 40°C.

[0211] Alternatively, for example, the reaction can be carried out in an organic solvent (dichloroethane, dichloromethane, toluene, tetrahydrofuran, a mixed solvent thereof, etc.) in the presence of a tertiary amine (triethylamine, diisopropylethylamine, etc.) using a Lewis acid (titanium tetrachloride, etc.) at 0 to 40°C, and further in the presence of a reducing agent (sodium triacetoxyborohydride, sodium cyanoborohydride, 2-picoline borane complex, etc.) at a temperature of 0 to 40°C.

[0212] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0213] The compound represented by general formula (IA-1) can be produced by subjecting a compound represented by general formula (XIX-1) and a compound represented by general formula (XI) to a coupling reaction.

[0214] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (IA).

[0215] The compound represented by general formula (IA-1) can also be prepared by the methods shown in the following reaction schemes 1-1c and 1-1d, in which all symbols have the same meanings as defined above.

[0216] [ka]

[0217] [ka]

[0218] The compound represented by the general formula (XXX-1) can be produced by subjecting the compound represented by the general formula (VII-1) to a deprotection reaction of the protecting group of the carboxyl group.

[0219] The deprotection reaction of the carboxyl protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (VIII).

[0220] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0221] The compound represented by general formula (XXXI-1) can be produced by subjecting a compound represented by general formula (XXX-1) and a compound represented by general formula (XI) to a coupling reaction.

[0222] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (IA).

[0223] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0224] The compound represented by general formula (XXXII-1) can be produced by subjecting a compound represented by general formula (XXXI-1) and a compound represented by general formula (IX) to an amidation reaction.

[0225] This amidation reaction is the same as the reaction used to produce the compound represented by the above-mentioned general formula (X).

[0226] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0227] The compound represented by the general formula (XXXIII-1) can be produced by subjecting the compound represented by the general formula (XXXII-1) to a deprotection reaction of the amino-protecting group.

[0228] The deprotection reaction of the amino protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (XVI-1).

[0229] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0230] The compound represented by general formula (IA-1) can be produced by alkylating a compound represented by general formula (XXXIII-1) with a compound represented by general formula (XVII-1) or a compound represented by general formula (XVIII-1).

[0231] This alkylation reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (XIX-1).

[0232] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0233] The compound represented by general formula (IA-1) can also be prepared by the method shown in the following reaction scheme 1-1e: In reaction scheme 1-1e, all symbols have the same meanings as defined above.

[0234] [ka]

[0235] The compound represented by the general formula (XXXVIII-1) can be produced by subjecting the compound represented by the general formula (VII-1) to a deprotection reaction of the amino-protecting group.

[0236] The deprotection reaction of the amino protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (XVI-1).

[0237] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0238] The compound represented by general formula (XXXIX-1) can be produced by alkylating a compound represented by general formula (XXXVIII-1) with a compound represented by general formula (XVII-1), or a compound represented by general formula (XVIII-1).

[0239] This alkylation reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (XIX-1).

[0240] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0241] The compound represented by the general formula (XL-1) can be produced by subjecting the compound represented by the general formula (XXXIX-1) to a deprotection reaction of the protecting group of the carboxyl group.

[0242] The deprotection reaction of the carboxyl protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (VIII).

[0243] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0244] The compound represented by general formula (XLI-1) can be produced by subjecting a compound represented by general formula (XL-1) and a compound represented by general formula (XI) to a coupling reaction.

[0245] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (IA).

[0246] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0247] The compound represented by general formula (IA-1) can be produced by subjecting a compound represented by general formula (XLI-1) and a compound represented by general formula (IX) to an amidation reaction.

[0248] This amidation reaction is the same as the reaction used to produce the compound represented by the above-mentioned general formula (X).

[0249] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0250] The compound represented by general formula (XXXIX-1) can also be prepared by the method shown in the following reaction scheme 1-1f: In reaction scheme 1-1f, all symbols have the same meanings as defined above.

[0251] [ka]

[0252] The compound represented by general formula (IV-1f) can be produced by subjecting a compound represented by general formula (II) and a compound represented by general formula (III-1f) to an amino group introduction reaction.

[0253] The reaction for introducing this amino group is the same as the reaction for producing the compound represented by the above-mentioned general formula (IV).

[0254] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0255] The compound represented by general formula (VI-1f) can be produced by subjecting a compound represented by general formula (IV-1f) and a compound represented by general formula (V) to a coupling reaction.

[0256] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VI).

[0257] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0258] The compound represented by the general formula (XXXIX-1) can be produced by subjecting the compound represented by the general formula (VI-1f) to a cyclization reaction.

[0259] This cyclization reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VII).

[0260] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0261] Among the compounds represented by general formula (I), R 3 Ga-NR 22 R 23 and R 22 However, 1 to 5 R 30 benzene optionally substituted with X 1 , X 2 , and X 3 are each independently CH or CR 6 a compound of general formula (IB)

[0262] [ka]

[0263] (wherein w is an integer of 0 to 3, and the other symbols have the same meanings as defined above) can be produced by the method shown in the following reaction scheme 2. In reaction scheme 2, all symbols have the same meanings as defined above.

[0264] [ka]

[0265] The compound represented by general formula (IB) can be produced by subjecting a compound represented by general formula (X) and a compound represented by general formula (XII) to a coupling reaction.

[0266] This coupling reaction is known and can be carried out, for example, in an organic solvent (benzene, toluene, dimethylformamide, dimethylacetamide, 1,4-dioxane, tetrahydrofuran, methanol, acetonitrile, dimethoxyethane, acetone, or a mixture thereof, etc.), using a base (sodium ethylate, sodium butoxide, sodium hydroxide, potassium hydroxide, triethylamine, sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, thallium carbonate, tripotassium phosphate, cesium fluoride, barium hydroxide, tetrabutylammonium fluoride, lithium bis(trimethylsilyl)amide (LHMDS), etc.) or a mixture thereof, a phosphine ligand ((9,9)-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (Xanthos), dicyclohexyl methyl ester (DMT ... The reaction is carried out at temperatures between room temperature and 150°C in the presence of tetrakis(triphenylphosphine)palladium (Pd(PPh3)4), bis(triphenylphosphine)palladium dichloride (PdCl2(PPh3)2), palladium acetate (Pd(OAc)2), palladium black, 1,1'-bis(diphenylphosphinoferrocene)dichloropalladium (PdCl2(dppf)2), diallylpalladium dichloride (PdCl2(allyl)2), phenylbis(triphenylphosphine)palladium iodide (PpdI(PPh3)2), (1E,4E)-1,5-diphenyl-1,4-pentadiene-3-one-palladium (Pd2(dba)3)), etc.

[0267] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0268] In general formula (IB), R 2is a 5- to 7-membered nitrogen-containing saturated heterocycle, and R 15 However, 1 to 5 R 18 a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group, or a C1-8 haloalkyl group, that is, a compound represented by the general formula (IB-1):

[0269] [ka]

[0270] The compound represented by the formula (wherein all symbols have the same meanings as defined above) can be prepared by the method shown in the following reaction scheme 2-1: (wherein all symbols have the same meanings as defined above).

[0271] [ka]

[0272] The compound represented by general formula (IB-1) can be produced by subjecting a compound represented by general formula (XIX-1) and a compound represented by general formula (XII) to a coupling reaction.

[0273] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (IB).

[0274] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0275] The compound represented by general formula (IB-1) can also be prepared by the methods shown in the following reaction schemes 2-1c and 2-1d, in which all symbols have the same meanings as defined above.

[0276] [ka]

[0277] [ka]

[0278] The compound represented by general formula (XXXI-2) can be produced by subjecting a compound represented by general formula (XXX-1) and a compound represented by general formula (XII) to a coupling reaction.

[0279] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (IB).

[0280] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0281] The compound represented by general formula (XXXII-2) can be produced by subjecting a compound represented by general formula (XXXI-2) and a compound represented by general formula (IX) to an amidation reaction.

[0282] This amidation reaction is the same as the reaction used to produce the compound represented by the above-mentioned general formula (X).

[0283] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0284] The compound represented by the general formula (XXXIII-2) can be produced by subjecting the compound represented by the general formula (XXXII-2) to a deprotection reaction of the amino-protecting group.

[0285] The deprotection reaction of the amino protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (XVI-1).

[0286] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0287] The compound represented by general formula (IB-1) can be produced by alkylating a compound represented by general formula (XXXIII-2) with a compound represented by general formula (XVII-1) or a compound represented by general formula (XVIII-1).

[0288] This alkylation reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (XIX-1).

[0289] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0290] The compound represented by general formula (IB-1) can also be prepared by the method shown in the following reaction scheme 2-1e: In reaction scheme 2-1e, all symbols have the same meanings as defined above.

[0291] [ka]

[0292] The compound represented by general formula (XLI-2) can be produced by subjecting a compound represented by general formula (XL-1) and a compound represented by general formula (XII) to a coupling reaction.

[0293] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (IB).

[0294] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0295] The compound represented by general formula (IB-1) can be produced by subjecting a compound represented by general formula (XLI-2) and a compound represented by general formula (IX) to an amidation reaction.

[0296] This amidation reaction is the same as the reaction used to produce the compound represented by the above-mentioned general formula (X).

[0297] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0298] Among the compounds represented by general formula (I), R 3 Ga-NR 22 R 23 and R 23 is a hydrogen atom, 1 to 5 R 29 a C alkyl group optionally substituted with 1 to 5 R 29-1 a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2 is a C2-4 alkynyl group optionally substituted with 1 , X 2 , and X 3 are each independently CH or CR 6 Compounds of general formula (IC)

[0299] [ka]

[0300] (In the formula, R 23-1 is a hydrogen atom, 1 to 5 R 29 a C alkyl group optionally substituted with 1 to 5 R 29-1 a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2 represents a C2-4 alkynyl group optionally substituted by, and the other symbols have the same meanings as above. A compound represented by the formula (I) can be prepared by the method shown in the following reaction scheme 3. In reaction scheme 3, all symbols have the same meanings as above.

[0301] [ka]

[0302] The compound represented by general formula (IC) can be produced by subjecting a compound represented by general formula (X) and a compound represented by general formula (XXXIV) to an amino group introduction reaction.

[0303] This reaction for introducing an amino group is known and can be carried out, for example, by reacting in an organic solvent (dichloromethane, dichloroethane, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, etc.) in the presence or absence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, etc.) and in the presence or absence of a fluoride salt (potassium fluoride, cesium fluoride, etc.) at a temperature of room temperature to 180°C.

[0304] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0305] In general formula (IC), R 2 is a 5- to 7-membered nitrogen-containing saturated heterocycle, and R 15 However, 1 to 5 R 18 a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group, or a C1-8 haloalkyl group, i.e., a compound represented by the general formula (IC-1):

[0306] [ka]

[0307] The compound represented by the formula (wherein all symbols have the same meanings as defined above) can be prepared by the method shown in the following reaction scheme 3-1: (wherein all symbols have the same meanings as defined above).

[0308] [ka]

[0309] The compound represented by general formula (IC-1) can be produced by subjecting a compound represented by general formula (XIX-1) and a compound represented by general formula (XXXIV) to an amino group introduction reaction.

[0310] The reaction for introducing this amino group is the same as the reaction for producing the compound represented by the above-mentioned general formula (IC).

[0311] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0312] The compound represented by general formula (IC-1) can also be prepared by the methods shown in the following reaction schemes 3-1c and 3-1d, in which all symbols have the same meanings as defined above.

[0313] [ka]

[0314] [ka]

[0315] The compound represented by general formula (XXXI-3) can be produced by subjecting a compound represented by general formula (XXX-1) and a compound represented by general formula (XXXIV) to an amino group introduction reaction.

[0316] The reaction for introducing this amino group is the same as the reaction for producing the compound represented by the above general formula (IC-1).

[0317] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0318] The compound represented by general formula (XXXII-3) can be produced by subjecting a compound represented by general formula (XXXI-3) and a compound represented by general formula (IX) to an amidation reaction.

[0319] This amidation reaction is the same as the reaction used to produce the compound represented by the above-mentioned general formula (X).

[0320] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0321] The compound represented by the general formula (XXXIII-3) can be produced by subjecting the compound represented by the general formula (XXXII-3) to a deprotection reaction of the amino-protecting group.

[0322] The deprotection reaction of the amino protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (XVI-1).

[0323] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0324] The compound represented by general formula (IC-1) can be produced by alkylating a compound represented by general formula (XXXIII-3) with a compound represented by general formula (XVII-1) or a compound represented by general formula (XVIII-1).

[0325] This alkylation reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (XIX-1).

[0326] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0327] The compound represented by general formula (IC-1) can also be prepared by the method shown in the following reaction scheme 3-1e: In reaction scheme 3-1e, all symbols have the same meanings as defined above.

[0328] [ka]

[0329] The compound represented by general formula (XLI-3) can be produced by subjecting a compound represented by general formula (XL-1) and a compound represented by general formula (XXXIV) to an amino group introduction reaction.

[0330] The reaction for introducing this amino group is the same as the reaction for producing the compound represented by the above-mentioned general formula (IC).

[0331] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0332] The compound represented by general formula (IC-1) can be produced by subjecting a compound represented by general formula (XLI-3) and a compound represented by general formula (IX) to an amidation reaction.

[0333] This amidation reaction is the same as the reaction used to produce the compound represented by the above-mentioned general formula (X).

[0334] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0335] The compound represented by general formula (IX) can be prepared by the method shown in the following reaction scheme 4. In reaction scheme 4, P N-2represents an amino-protecting group (e.g., benzyloxycarbonyl group, tert-butoxycarbonyl group, allyloxycarbonyl (Alloc) group, 1-methyl-1-(4-biphenyl)ethoxycarbonyl (Bpoc) group, trifluoroacetyl group, 9-fluorenylmethoxycarbonyl group, benzyl (Bn) group, 4-methoxybenzyl group, benzyloxymethyl (BOM) group, 2-(trimethylsilyl)ethoxymethyl (SEM), fluorenylcarbonyl group, trityl group, and o-nitrobenzenesulfenyl group), and E 3 represents a leaving group, and the other symbols have the same meanings as above.

[0336] [ka]

[0337] The compound represented by general formula (XV) can be produced by subjecting a compound represented by general formula (XIII) and a compound represented by general formula (XIV) to an alkylation reaction.

[0338] This alkylation reaction is known and can be carried out, for example, in an organic solvent (tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, etc.) in the presence of a base (sodium hydride, potassium hydride, sodium butoxide, potassium carbonate, cesium carbonate, etc.) in the presence or absence of a catalyst (potassium iodide, sodium iodide, tetrabutylammonium iodide, etc.) at a temperature of 0°C to reflux.

[0339] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0340] The compound represented by the general formula (IX) can be produced by subjecting the compound represented by the general formula (XV) to a deprotection reaction of the amino-protecting group.

[0341] The deprotection reaction of the amino protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (XVI-1).

[0342] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0343] The compound represented by general formula (IV) can also be produced by subjecting a compound represented by general formula (XX) to an amino group introduction reaction and then subjecting the resulting compound represented by general formula (XXI) to a reduction reaction, as shown in the following reaction scheme 5. In reaction scheme 5, all symbols have the same meanings as above.

[0344] [ka]

[0345] The compound represented by general formula (XXI) can be produced by subjecting a compound represented by general formula (XX) and a compound represented by general formula (III) to an amino group introduction reaction.

[0346] This reaction for introducing an amino group is known and can be carried out, for example, by reacting in an organic solvent (dichloromethane, tetrahydrofuran, 1,4-dioxane, dimethylformamide, dimethylacetamide, 1-methyl-2-pyrrolidone, etc.) in the presence of a base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, etc.) at a temperature of −20° C. to room temperature.

[0347] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0348] The compound represented by the general formula (IV) can be produced by subjecting the compound represented by the general formula (XXI) to a reduction reaction.

[0349] This reduction reaction is known and is carried out, for example, in a water-miscible solvent (ethanol, methanol, tetrahydrofuran, etc.) in the presence or absence of an acid (hydrochloric acid, hydrobromic acid, ammonium chloride, acetic acid, ammonium formate, etc.) using a metal reagent (zinc, iron, tin, tin chloride, iron chloride, samarium, indium, sodium borohydride-nickel chloride, etc.) at a temperature of 0 to 150°C.

[0350] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0351] The compound represented by formula (X) can also be produced by the method shown in the following reaction scheme 6. In reaction scheme 6, P N-3 represents a protecting group for an amino group (e.g., 2,4-dimethoxybenzyl, 4-methoxybenzyl, etc.), E 5 represents a leaving group (for example, a fluorine atom, a bromine atom, a chlorine atom, an iodine atom, a trifluoromethanesulfonate ester, a p-toluenesulfonate ester, etc.), and the other symbols have the same meanings as above.

[0352] [ka]

[0353] The compound represented by general formula (XXIII) can be produced by subjecting a compound represented by general formula (II) and a compound represented by general formula (XXII) to an amino group introduction reaction.

[0354] The reaction for introducing this amino group is the same as the reaction for producing the compound represented by the above-mentioned general formula (IV).

[0355] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0356] The compound represented by the general formula (XXIV) can be produced by subjecting the compound represented by the general formula (XXIII) to a cyclization reaction.

[0357] This cyclization reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VII).

[0358] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0359] The compound represented by general formula (XXV) can be produced by subjecting a compound represented by general formula (XXIV) and a compound represented by general formula (XXXV) to a coupling reaction.

[0360] This coupling reaction is known and can be carried out, for example, in an organic solvent (dichloromethane, acetonitrile, etc.) in the presence of a base (pyridine, triethylamine, N,N-diisopropylethylamine, etc.), a copper salt (e.g., copper(II) acetate, etc.) and a desiccant (e.g., molecular sieves, etc.) at room temperature to 120°C.

[0361] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0362] The compound represented by the general formula (XXVI) can be produced by subjecting the compound represented by the general formula (XXV) to a deprotection reaction of the protecting group for the carboxyl group.

[0363] The deprotection reaction of the carboxyl protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (VIII).

[0364] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0365] The compound represented by general formula (XXVII) can be produced by subjecting a compound represented by general formula (XXVI) and a compound represented by general formula (IX) to an amidation reaction.

[0366] This amidation reaction is the same as the reaction used in producing the compound represented by the above-mentioned general formula (X).

[0367] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0368] The compound represented by the general formula (XXVIII) can be produced by subjecting the compound represented by the general formula (XXVII) to a deprotection reaction of the amino-protecting group.

[0369] The deprotection reaction of the protecting group of this amino group is known and can be carried out, for example, by reacting in an organic solvent (dichloromethane, chloroform, toluene, 1,4-dioxane, dimethoxyethane, etc.) or without a solvent in the presence of an acid (trifluoroacetic acid, etc.) and a reducing agent (triethylsilane) at room temperature to reflux temperature.

[0370] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0371] The compound represented by general formula (X) can be produced by alkylating a compound represented by general formula (XXVIII) and a compound represented by general formula (XXIX).

[0372] This alkylation reaction is known and can be carried out, for example, in an organic solvent (dimethylformamide, dimethylacetamide, dimethyl sulfoxide, chloroform, dichloromethane, diethyl ether, tetrahydrofuran, methyl t-butyl ether, etc.) at 0 to 100°C in the presence of an organic base (triethylamine, N,N-diisopropylethylamine, pyridine, 4-dimethylaminopyridine, N-methylmorpholine, etc.), an alkali metal hydroxide (sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), an alkaline earth metal hydroxide (barium hydroxide, calcium hydroxide, etc.) or carbonate (sodium carbonate, potassium carbonate, etc.), or an aqueous solution thereof, or a mixture thereof, in the presence or absence of an alkali metal halide salt (potassium iodide, sodium iodide, etc.).

[0373] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0374] The compound represented by general formula (X) can also be prepared by the method shown in the following reaction scheme 7. In reaction scheme 7, all symbols have the same meanings as defined above.

[0375] [ka]

[0376] The compound represented by general formula (XXXVII) can be produced by subjecting a compound represented by general formula (IX) and a compound represented by general formula (XXXVI) to an amidation reaction.

[0377] This amidation reaction is the same as the reaction used in producing the compound represented by the above-mentioned general formula (X).

[0378] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0379] The compound represented by general formula (XXXVIII) can be produced by subjecting a compound represented by general formula (XXXVII) and a compound represented by general formula (IV) to a coupling reaction.

[0380] This coupling reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VI).

[0381] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0382] The compound represented by the general formula (X) can be produced by subjecting the compound represented by the general formula (XXXVIII) to a cyclization reaction.

[0383] This cyclization reaction is the same as the reaction used to prepare the compound represented by the above-mentioned general formula (VII).

[0384] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0385] Among the compounds represented by general formula (IX), compounds in which s is 0, that is, compounds represented by general formula (IX-1)

[0386] [ka]

[0387] A compound of the formula: (wherein all symbols have the same meanings as defined above) can be prepared by the method shown in the following Reaction Scheme 8: In Reaction Scheme 8, all symbols have the same meanings as defined above.

[0388] [ka]

[0389] The compound represented by the general formula (XLIII) can be produced by subjecting the compound represented by the general formula (XLII) to a dimethylaminomethylation reaction.

[0390] This dimethylaminomethylation reaction is known and can be carried out, for example, by reacting dimethylamine and formaldehyde in the presence of an acid (e.g., hydrogen chloride, sulfuric acid, acetic acid, trifluoroacetic acid, etc.) in an organic solvent (e.g., methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, water, or a mixed solvent thereof, etc.) at a temperature of 0°C to reflux.

[0391] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0392] The compound represented by the general formula (XLIV) can be produced by subjecting the compound represented by the general formula (XLIII) to a reaction for introducing a nitrile group.

[0393] This reaction for introducing a nitrile group is known and can be carried out, for example, by reacting the compound with a methylating agent (dimethyl sulfate, methyl iodide, etc.) in an organic solvent (acetonitrile, tetrahydrofuran, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, dimethylformamide, dimethylacetamide, 1-methyl-2-pyrrolidone, water, or a mixed solvent thereof, etc.) at 0°C to room temperature, and then reacting the resulting ammonium salt with a cyanating agent (potassium cyanide, sodium cyanide, etc.) at a temperature of 0°C to 100°C.

[0394] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0395] The compound represented by the general formula (XLV) can be produced by subjecting the compound represented by the general formula (XLIV) to a reduction reaction.

[0396] This reduction reaction is known and can be carried out, for example, by reacting in an organic solvent (methanol, ethanol, tetrahydrofuran, diethyl ether, etc.) in the presence of a reducing agent (lithium aluminum hydride, bis(2-methoxyethoxy)alkylsodium hydride, diisobutylaluminum hydride, lithium borohydride, sodium borohydride, nickel boride, borane-pyridine complex, borane-tetrahydrofuran complex, etc.), or in the presence of a reducing agent (lithium borohydride, sodium borohydride, etc.) and an acid (trifluoroacetic acid, etc.) at a temperature of about −10° C. to reflux. Furthermore, in an inert solvent [ethers (e.g., tetrahydrofuran, 1,4-dioxane, dimethoxyethane, diethyl ether, etc.), alcohols (e.g., methanol, ethanol, etc.), benzenes (e.g., benzene, toluene, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g., acetonitrile, etc.), amides (e.g., dimethylformamide, etc.), water, ethyl acetate, acetic acid, or a mixture of two or more thereof, etc.], a hydrogenation catalyst (e.g., palladium carbon, palladium black, palladium, palladium hydroxide, etc.), The reaction is carried out in the presence of an inorganic acid (e.g., hydrochloric acid, sulfuric acid, hypochlorous acid, boric acid, tetrafluoroboric acid, etc.) or an organic acid (e.g., acetic acid, p-toluenesulfonic acid, oxalic acid, trifluoroacetic acid, formic acid, etc.) or a base (lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium carbonate, ammonia, triethylamine, etc.) at a temperature of 0 to 200°C under a hydrogen atmosphere at normal or elevated pressure or in the presence of ammonium formate. When an inorganic or organic acid is used, its salt may also be used.

[0397] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0398] The compound represented by the general formula (XLVI) can be produced by subjecting the compound represented by the general formula (XLV) to a cyclization reaction.

[0399] This cyclization reaction is known and can be carried out, for example, by reacting the compound with formaldehyde in the presence of an acid (e.g., hydrogen chloride, sulfuric acid, acetic acid, trifluoroacetic acid, etc.) in an organic solvent (e.g., tetrahydrofuran, dichloromethane, chloroform, benzene, toluene, xylene, hexane, heptane, cyclohexane, diethyl ether, 1,4-dioxane, acetone, ethyl methyl ketone, acetonitrile, dimethyl sulfoxide, dimethylformamide, dimethylacetamide, ethyl acetate, etc.) at a temperature of 0°C to reflux.

[0400] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0401] The compound represented by the general formula (XLVII) can be produced by subjecting the compound represented by the general formula (XLVI) to a reaction for introducing a protecting group for the amino group.

[0402] Introduction of a protecting group for the amino group is known, and can be performed, for example, using the protecting group introduction reaction described in "PGM Wuts, TW Greene, Green's Protective Groups in Organic Synthesis, Wiley, Fourth Edition, New York, 2007." For example, introduction of a protecting group such as a tert-butoxycarbonyl group, benzyloxycarbonyl group, fluorenylcarbonyl group, trityl group, or o-nitrobenzenesulfenyl group can be performed by using di-tert-butyl dicarbonate, benzyloxycarbonyl chloride, fluorenylcarbonyl chloride, trityl chloride, or o-nitrobenzenesulfenyl chloride, respectively, in a solvent such as dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran, dioxane, toluene, ethyl acetate, or water at −50 to 100° C. In this case, if necessary, a base such as amines such as triethylamine and diisopropylethylamine, organic acid salts such as sodium 2-ethylhexanoate and potassium 2-ethylhexanoate, or inorganic bases such as sodium hydroxide and potassium carbonate can be used.

[0403] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0404] The compound represented by the general formula (XLVIII) can be produced by subjecting a compound represented by the general formula (XLVII) and a compound represented by the general formula (XIV) to an alkylation reaction.

[0405] This alkylation reaction is known and is similar to the reaction used in producing the compound represented by the above-mentioned general formula (XV).

[0406] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0407] The compound represented by the general formula (IX-1) can be produced by subjecting the compound represented by the general formula (XLVIII) to a deprotection reaction of the protecting group of the amino group.

[0408] The deprotection reaction of the amino protecting group is the same as the reaction used in producing the compound represented by the above-mentioned general formula (XVI-1).

[0409] If necessary, this reaction may be followed by a known method to convert the compound into the desired salt.

[0410] In each reaction in the present specification, compounds used as starting materials and compounds or reagents added, for example, compounds represented by general formulae (II), (III), (III-1), (III-1f), (V), (IX), (XI), (XII), (XIII), (XIV), (XVII-1), (XVIII-1), (XX), (XXII), (XXIX), (XXXIV), (XXXV), (XXXVI), and (XLII), are either known or can be prepared according to known methods or methods described in the Examples.

[0411] Among the compounds used in the present invention, optically active compounds can be produced by using optically active starting materials or reagents, by optically resolving a racemic intermediate and then converting it into the compound used in the present invention, or by optically resolving a racemic compound. Methods for this optical resolution are well known, and include, for example, forming a salt or complex with another optically active compound, recrystallizing it, and then isolating the target compound or directly separating it using a chiral column or the like.

[0412] In each reaction herein, reactions involving heating can be carried out using a water bath, oil bath, sand bath or microwave, as will be apparent to those skilled in the art.

[0413] In each reaction herein, a solid-phase-supported reagent supported on a high molecular weight polymer (for example, polystyrene, polyacrylamide, polypropylene, polyethylene glycol, etc.) may be used as appropriate.

[0414] In each reaction in this specification, the reaction product can be purified by a conventional purification means, for example, distillation under atmospheric pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium silicate, thin layer chromatography, ion exchange resin, scavenger resin or column chromatography, washing or recrystallization, etc. Purification may be carried out for each reaction or may be carried out after completion of some reactions.

[0415] [toxicity] The toxicity of the compounds of the present invention is sufficiently low and they can be used safely as pharmaceuticals. [Application to pharmaceuticals] The compounds of the present invention have inhibitory activity against one or both of DGKα and DGKζ and can therefore be prescribed as agents for inhibiting the progression, suppressing recurrence, and / or treating diseases associated with DGKα and / or DGKζ in mammals, particularly humans (human patients). Examples of diseases associated with DGKα and / or DGKζ include cancer and infectious diseases. That is, the compounds of the present invention can be prescribed as effective agents for inhibiting the progression, suppressing recurrence, and / or treating cancer or infectious diseases.

[0416] As used herein, "cancer treatment" includes, for example, treatments performed to (a) reduce cancer cell proliferation, (b) reduce symptoms caused by cancer and improve the quality of life of cancer patients, (c) reduce the dose of other anticancer drugs or adjuvant cancer treatment drugs already administered, and / or (d) extend the survival time of cancer patients. Furthermore, "suppressing cancer progression" means delaying cancer progression, stabilizing cancer-related symptoms, and reversing the progression of symptoms. "Suppressing recurrence" means preventively preventing cancer recurrence in patients whose cancer lesions have completely or substantially disappeared or been removed by cancer treatment or surgical resection.

[0417] Furthermore, the compound of the present invention may be prescribed to (a) patients with cancer for which the therapeutic effect of other cancer treatments has been insufficient or insufficient or which has progressed after other cancer treatments, (b) patients with curable or unresectable, metastatic, recurrent, refractory and / or distant metastatic cancer, (c) patients with cancer in which TPS or CPS is 50% or more, 25% or more, 10% or more, 5% or more, or 1% or more, (d) patients with cancer with MSI-H or dMMR, (e) patients with BRAF V600E mutation-positive malignant melanoma or non-small cell lung cancer, (f) patients with cancer that is EGFR gene mutation-positive or ALK fusion gene-positive, or (g) patients with cancer in which TMB is frequent.

[0418] On the other hand, the compound of the present invention may be more likely to be prescribed to (a) cancer patients who have not received other cancer treatments, (b) cancer patients with TPS or CPS of less than 50%, less than 25%, less than 10%, less than 5%, or less than 1%, (c) cancer patients with no MSI-H and / or dMMR or with MSI-L, (d) BRAF V600 wild-type melanoma or non-small cell lung cancer patients, (e) EGFR gene mutation-negative and / or ALK fusion gene-negative non-small cell lung cancer patients, or (f) cancer patients with a low frequency of TMB.

[0419] It can also be prescribed as a postoperative adjuvant therapy to prevent recurrence or metastasis after surgical resection of cancer, or as a neoadjuvant therapy performed before surgical resection.

[0420] Here, "other cancer treatments" include the anticancer drugs listed in the "Concomitant or Combined Drugs" section below, i.e., alkylating agents, platinum compounds, antimetabolites (e.g., antifolates, pyridine metabolic inhibitors, and purine metabolic inhibitors), ribonucleotide reductase inhibitors, nucleotide analogs, topoisomerase inhibitors, microtubule polymerization inhibitors, microtubule depolymerization inhibitors, antitumor antibiotics, cytokines, antihormones, molecularly targeted drugs, and cancer immunotherapy drugs, as well as radiation therapy, transarterial chemoembolization (TACE), transarterial embolization (TAE), cancer vaccines, and immune cell therapy. Furthermore, "insufficient or insufficient therapeutic effects of other cancer treatments" include, for example, cases where treatment with existing anticancer drugs results in "stable (SD)" or "progressed (PD)" according to the RECIST (Reported Investigator of Cancer Infectious Diseases) assessment.

[0421] Cancers that the compound of the present invention is intended to treat and / or inhibit progression of include all solid cancers and blood cancers. Among solid cancers, epithelial cell cancers include, for example, malignant melanoma (e.g., malignant melanoma of the skin, oral mucosal epithelium, or orbital cavity), non-small cell lung cancer (e.g., squamous non-small cell lung cancer and non-squamous non-small cell lung cancer), small cell lung cancer, head and neck cancer (e.g., oral cancer, nasopharyngeal cancer, oropharyngeal cancer, hypopharyngeal cancer, laryngeal cancer, salivary gland cancer, and tongue cancer), renal cell carcinoma (e.g., clear cell renal cell carcinoma), breast cancer, ovarian cancer (e.g., serous ovarian cancer and ovarian clear cell adenocarcinoma), nasopharyngeal cancer, uterine cancer (e.g., cervical cancer and endometrial cancer), anal cancer (e.g., anal canal cancer), colorectal cancer (e.g., , MSI-H and / or dMMR-positive colorectal cancer), rectal cancer, colon cancer, hepatocellular carcinoma, esophageal cancer, gastric cancer, esophagogastric junction cancer, pancreatic cancer, urothelial cancer (e.g., bladder cancer, upper urinary tract cancer, ureteral cancer, renal pelvic cancer, and urethral cancer), prostate cancer, fallopian tube cancer, primary peritoneal cancer, malignant pleural mesothelioma, gallbladder cancer, bile duct cancer, biliary tract cancer, skin cancer (e.g., uveal melanoma and Merkel cell carcinoma), testicular cancer (germ cell tumor), vaginal cancer, vulvar cancer, penile cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal gland cancer, spinal tumor, neuroblastoma, medulloblastoma, ocular retinoblastoma, neuroendocrine tumor, brain tumor (e.g., glioma (e.g., glioblastoma and gliosarcoma) and meningioma), and squamous cell carcinoma.

[0422] Among solid cancers, sarcomas include bone and soft tissue sarcomas (for example, Ewing's sarcoma, childhood rhabdomyosarcoma, uterine leiomyosarcoma, chondrosarcoma, pulmonary sarcoma, osteosarcoma, and congenital fibrosarcoma), Kaposi's sarcoma, and the like.

[0423] Examples of blood cancers include multiple myeloma, malignant lymphomas (e.g., non-Hodgkin's lymphoma (e.g., follicular lymphoma, precursor B-cell lymphoblastic lymphoma, chronic B-lymphocytic leukemia, nodal marginal zone B-cell lymphoma, diffuse large B-cell lymphoma, MALT lymphoma, primary splenic marginal zone B-cell lymphoma, hairy cell leukemia, primary mediastinal large B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma, mycosis fungoides, Sezary syndrome, chronic or acute lymphocytic leukemia, precursor T-cell lymphoblastic lymphoma, chronic T-lymphocytic leukemia, large granular T-cell leukemia, , large granular NK-cell leukemia, peripheral T-cell lymphoma, extranodal NK / T-cell lymphoma, adult T-cell leukemia, angiocentric lymphoma, intestinal T-cell lymphoma, Hodgkin-like / Hodgkin-related anaplastic large cell lymphoma, B-cell lymphoblastic leukemia, T-cell lymphoblastic leukemia, lymphoplasmacytic lymphoma, and primary central nervous system malignant lymphoma) and Hodgkin lymphoma (e.g., classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma)) and leukemia (e.g., acute myeloid leukemia and chronic myeloid leukemia), myelodysplastic syndromes, and myeloproliferative disorders.

[0424] Furthermore, cancers that the compound of the present invention can treat and / or inhibit progression of include childhood cancers and cancers of unknown primary origin.

[0425] Infectious diseases that the compound of the present invention is intended to treat and / or inhibit progression of include symptoms caused by viral infection, parasitic infection, bacterial infection, or fungal infection.

[0426] Examples of viral infections include adenoviruses, arenaviruses, bunyaviruses, caliciviruses, coronaviruses, filoviruses, hepadnaviruses, herpesviruses, orthomyxoviruses, papovaviruses, paramyxoviruses, parvoviruses, picornaviruses, poxviruses, reoviruses, retroviruses, rhabdoviruses, togaviruses, papillomaviruses (e.g., human papillomaviruses (HPV)), human immunodeficiency virus (HIV), polioviruses, hepatitis viruses (e.g., hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV)), smallpox viruses (e.g., variola major and variola minor), vaccinia viruses, and influenza viruses. Examples of viruses that may be present include infections caused by rabies, rhinovirus, dengue virus, equine encephalitis virus, rubella virus, yellow fever virus, Norwalk virus, human T-cell leukemia virus (HTLV-I), hairy cell leukemia virus (HTLV-II), California encephalitis virus, hantavirus (hemorrhagic fever), rabies virus, Ebola virus, Marburg virus, measles virus, mumps virus, respiratory syncytial virus (RSV), herpes simplex type 1 (oral herpes), herpes simplex type 2 (genital herpes), herpes zoster (varicella-zoster virus), cytomegalovirus (CMV), Epstein-Barr virus (EBV), flavivirus, foot-and-mouth disease virus, chikungunya virus, Lassa virus, arenaviruses, or oncogenic viruses.

[0427] Examples of parasitic infections include acanthamoeba keratitis, amebiasis, ascariasis, babesiosis, balantidiosis, raccoon ascariasis, Chagas' disease, hepatic dystomatosis, cochliomia, cryptosporidiosis, diphyllobothriasis, dracunculiasis, echinococcosis, elephantiasis, enterobiasis, fascioliasis, fascioliasis, filariasis, giardiasis, gnathostomiasis, hymenoptera disease, isosporosis, Katayama fever, leishmaniasis, Lyme disease, malaria, yokogawa fluke disease, myiasis, onchocerciasis, pediculosis, scabies, schistosomiasis, African sleeping sickness, strongyloidiasis, taeniasis, toxocariasis, toxoplasmosis, trichinosis, and trichuriasis.

[0428] Examples of bacterial infections include those caused by antibiotic-resistant bacteria such as tuberculosis, anthrax, pathogenic bacteria, food poisoning bacteria, salmonella, staphylococci, streptococci, tetanus, mycobacteria, tetanus, plague, anthrax, and methicillin-resistant Staphylococcus aureus (MRSA), as well as infections caused by Clostridium difficile and other infectious bacteria.

[0429] Fungal infections include, for example, infections caused by Aspergillus species, Blastomyces dermatitidis, Candida yeasts (e.g., Candida albicans), Coccidioides, Cryptococcus neoformans, Cryptococcus gattii, dermatophytes, Fusarium species, Histoplasma capsulatum, Mucocomycota, Pneumocystis jiroveci, Sporothrix schenckii, Exserohyllum species, or Cladosporium. [Combined or combined drugs] The compound of the present invention or a pharmaceutical composition containing the compound of the present invention as an active ingredient (hereinafter sometimes abbreviated as "the compound of the present invention, etc.") may be formulated in combination with one or more other drugs for the purposes of (a) inhibiting the progression, suppressing recurrence, and / or enhancing the therapeutic effect of cancer or infectious diseases, (b) reducing the dosage of other drugs prescribed in combination, (c) reducing the side effects of other drugs prescribed in combination, and / or (d) enhancing the immune-enhancing effect of other drugs prescribed in combination, i.e., as an adjuvant. In the present invention, when formulated in combination with other drugs, the dosage form may be a combination formulation in which both components are combined in a single formulation, or may be administered as separate formulations. Such combined use can complement the preventive, symptom progression suppression, recurrence suppression, and / or therapeutic effect of the other drug, or maintain or reduce the dosage or frequency of administration. When the compound of the present invention, etc. and the other drug are formulated separately, they may be administered simultaneously for a certain period of time, and then the compound of the present invention, etc., or the other drug may be administered alone. Furthermore, the compound of the present invention or the like may be administered first, followed by the other drug, or the other drug may be administered first, followed by the compound of the present invention or the like. Furthermore, during the administration, there may be a period during which both drugs are administered simultaneously. The administration methods for each drug may be the same or different. Depending on the properties of the drugs, a kit containing a formulation containing the compound of the present invention and another formulation containing the other drug may also be provided. The dosage of the other drug can be appropriately selected based on the dose used in clinical practice. Any two or more other drugs may be administered in combination at an appropriate ratio. The other drugs include not only those discovered so far, but also those to be discovered in the future.

[0430] Examples of anticancer agents that can be used in combination with the compound of the present invention in cancer treatment include alkylating agents (e.g., dacarbazine, nimustine, temozolomide, fotemustine, bendamustine, cyclophosphamide, ifosfamide, carmustine, chlorambucil, and procarbazine, etc.), platinum compounds (e.g., cisplatin, carboplatin, nedaplatin, and oxaliplatin, etc.), antimetabolites (e.g., antifolates (e.g., pemetrexed, leucovorin, and methotrexate, etc.)), pyridine metabolism inhibitors (e.g., TS-1 (registered trademark), 5-fluorouracil, UF T, Carmofur, Doxifluridine, FdUrd, Cytarabine, and Capecitabine, etc.), purine metabolism inhibitors (e.g., Fludarabine, Cladribine, and Nelarabine, etc.), ribonucleotide reductase inhibitors, nucleotide analogs (e.g., Gemcitabine, etc.), topoisomerase inhibitors (e.g., Irinotecan, Nogitecan, and Etoposide, etc.), microtubule polymerization inhibitors (e.g., Vinblastine, Vincristine, Vindesine, Vinorelbine, Eribulin, etc.), microtubule depolymerization inhibitors (e.g., Docetaxel and Paclitaxel), antitumor antibiotics (e.g., Bleomycin, Mitomycin, etc.),C, Doxorubicin, Daunorubicin, Idarubicin, Etoposide, Mitoxantrone, Vinblastine, Vincristine, Peplomycin, Amrubicin, Aclarubicin, and Epirubicin, etc.), cytokine preparations (e.g., IFN-α2a, IFN-α2b, PEG-IFN-α2b, natural IFN-β, and Interleukin-2, etc.), antihormonal drugs (e.g., Tamoxifen, Fulvestrant, Goserelin, Leuprorelin, Anastrozole, Letrozole, and Exemestane, etc.), molecularly targeted drugs, cancer immunotherapy drugs, and other antibody pharmaceuticals.

[0431] Examples of molecular targeted drugs include ALK inhibitors (e.g., Crizotinib, Ceritinib, Ensartinib, Alectinib, and Lorlatinib), BCR-ABL inhibitors (e.g., Imatinib and Dasatinib), EGFR inhibitors (e.g., Erlotinib, EGF816, Afatinib, and Osimertinib), and mesylate, Gefitinib, and Rociletinib), B-Raf inhibitors (e.g., Sorafenib, Vemurafenib, TAK-580, Dabrafenib, Encorafenib, LXH254, Emurafenib, and BGB-3111), VEGFR inhibitors (e.g., Bevacizumab, Apatinib, Lenvatinib, Aflibercept, and Axitinib), FGFR inhibitors (e.g., AZD4547, B-701, FGF401, and INCB054828), c-Met inhibitors (e.g., Savolitinib, Merestinib, Capmatinib, INC280, and Glesati nib), Axl inhibitors (e.g., ONO-7475 and BGB324), Mek inhibitors (e.g., Cobimetinib, Binimetinib, Selumetinib, and Trametinib), CDK inhibitors (e.g., Dinaciclib, Abemaciclib, Palbociclib, and Trilaciclib), Btk inhibitors (e.g., ONO-4059, Ibrutinib, and Acalabrutinib), PI3K-δ / γ inhibitors (e.g., TGR-1202, INCB050465, and IPI-549), JAK-1 / 2 inhibitors (e.g., Itacitinib and Ruxolitinib), ERK inhibitors (e.g., SCH 900353), TGFbR1 inhibitors (e.g., Galunisertib), Cancer cell stemness kinase inhibitors (e.g., Amcasertib), FAK inhibitors (e.g., Defactinib), Syk / FLT3Dual inhibitors (e.g., TAK-659), ATR inhibitors (e.g., AZD6738), Wee1 kinase inhibitors (e.g., AZD1775), multi-tyrosine kinase inhibitors (e.g., Sunitinib, Pazopanib, Cabozantinib, Regorafenib, Nintedanib, Sitravatinib, and Midostaurin), mTOR inhibitors (e.g., Temsirolimus, Everolimus, Vistusertib, Irinotecan), HDAC inhibitors (e.g., Vorinostat, Romidepsin, Entinostat, Chidamide, Mocetinostat, Citarinostat, stat, Panobinostat, Valproate), PARP inhibitors (e.g., Niraparib, Olaparib, Veliparib, Rucaparib, Beigene-290), aromatase inhibitors (e.g., Exemestane, Letrozole), EZH2 inhibitors (e.g., tazemetostat), galectin-3 inhibitors (e.g., GR-MD-02), STAT3 inhibitors (e.g., Napabucasin), DNMT inhibitors (e.g., Azacitidine), SMO inhibitors (e.g., Vismodegib), Hsp90 inhibitors (e.g., XL888), γ-tubulin-specific inhibitors (e.g., Glaziovianin A, Plinabulin), HIF2α inhibitors (e.g., PT2385), glutaminase inhibitors (e.g., CB-839), E3 ligase inhibitors (e.g., Avadomide), Nrf2 activators (e.g., Omaveloxolone), arginase inhibitors (e.g., CB-1158), cell cycle inhibitors (e.g., Trabectedin), Ephrin B4 inhibitors (e.g., sEphB4-HAS), IAP antagonists (e.g., Birinapant), BET protein inhibitors (e.g., CC-90010), LSD1 inhibitors (e.g., CC-90011), CRBN regulators (e.g., Avadomide), anti-Her2 antibodies (e.g., Trastuzumab,emtansine, Pertuzumab, and Margetuximab), anti-EGFR antibodies (e.g., Cetuximab, Panitumumab, Necitumumab, and Nimotuzumab), anti-VEGF antibodies (e.g., Bevacizumab), anti-VEGFR2 antibodies (e.g., Ramucirumab), anti-CD20 antibodies (e.g., Rituximab, Ofatumumab, Ublituximab, and Obinutuzumab), anti-CD30 antibodies (e.g., Brentuximab Vedotin), anti-CD38 antibodies (e.g., Daratumumab), anti-DR5 antibodies (e.g., DS-8273a), anti-CA125 antibodies (e.g., Oregovomab), anti-DLL4 antibodies (e.g., Demcizumab), anti-fucosyl GM1 antibodies (e.g., BMS-986012), anti-gpNMB antibodies (e.g., Glembatumumab vedotin), anti-Mesothelin antibody (e.g., BMS-986148), anti-MMP9 antibody (e.g., Andecaliximab), anti-GD2 antibody (e.g., Dinutuximab-β), anti-c-Met antibody (e.g., ABT-399), anti-FOLR1 antibody (e.g., Mirvetuximab soravtansine), anti-Fucosyl-GM1 antibody (e.g., BMS-986012), anti-Ang2-VEGF bispecific antibody (e.g., Vanucizumab), anti-CD30-CD16A bispecific antibody (e.g., AFM13), anti-CD79b antibody (e.g., Polatuzumab Vedotin), anti-FAP antibody / IL-2 fusion protein (e.g., RO6874281), anti-CEA antibody / IL-2 fusion protein (e.g., Cergutuzumab amunaleukin), anti-CEA-CD3 bispecific antibodies (e.g., RO6958688), anti-DLL3 antibodies (e.g., robalpituzumab tesirine), anti-CD3-CD19 bispecific antibodies (e.g., blinatumomab), and anti-CD20-CD3 bispecific antibodies (e.g., REGN1979).

[0432] Furthermore, examples of cancer immunotherapeutic drugs include anti-PD-1 antibodies (e.g., Nivolumab, Cemiplimab (REGN-2810), Pembrolizumab (MK-3475), Spartalizumab (PDR-001), Tislelizumab (BGB-A317), AMP-514 (MEDI0680), Dostarlimab (ANB011 / TSR-042), Toripalimab (JS001), Camrelizumab (SHR-1210), Genolimzumab (CBT-501), Sintilimab (IBI308), STI-A1110, ENUM 388D4, ENUM 244C8, GLS010, MGA012, AGEN2034, CS1003, HLX10, BAT-1306, AK105, AK103, BI 754091, LZM009, CMAB819, Sym021, GB226, SSI-361, JY034, HX008, ABBV181, BCD-100, PF-06801591, CX-188, JNJ-63723283, and AB122, etc.), anti-PD-L1 antibodies (e.g., atezolizumab (RG7446 / MPDL3280A), Av elumab(PF-06834635 / MSB0010718C), Durvalumab(MEDI4736), BMS-936559, STI-1014, KN035, LY3300054, HLX20, SHR-1316, CS1001, MSB2311, BGB-A333, KL-A167, CK-301, AK106, AK104, ZKAB 001, FAZ053, CBT-502, JS003, and CX-072, etc.), PD-1 antagonists (e.g., AUNP-12, and the compounds BMS-M1 to BMS-M10 (WO2014 / 151634, WO2016 / 039749, WO2016 / 057624, WO2016 / 077518, WO2016 / 100285, WO2016 / 100608 , WO2016 / 126646, WO2016 / 149351, WO2017 / 151830 and WO2017 / 176608), BMS-1, BMS-2, BMS-3, BMS-8, BMS-37, BMS-200, BMS-202, BMS-230, BMS-242, BMS-1001 and BMS-1166 (see WO2015 / 034820,WO2015 / 160641, WO2017 / 066227 and Oncotarget. 2017 Sep 22; 8(42): 72167-72181), Incyte-1 to Incyte-6 compounds (see WO2017 / 070089, WO2017 / 087777, WO2017 / 106634, WO2017 / 112730, WO2017 / 192961, and WO2017 / 205464), CAMC-1 to CAMC-4 (see WO2017 / 202273, WO2017 / 202274, WO2017 / 202275, and WO2017 / 202276), RG_1 (see WO2017 / 118762), and DPPA-1 (Angew. Chem. Int. Ed. 2015, 54, 11760-11764), etc.), PD-L1 / VISTA antagonists (e.g., CA-170), PD-L1 / TIM3 antagonists (e.g., CA-327), anti-PD-L2 antibodies, PD-L1 fusion proteins, PD-L2 fusion proteins (e.g., AMP-224), anti-CTLA-4 antibodies (e.g., ipilimumab (MDX-010), AGEN1884, and tremelimumab), anti-LAG-3 antibodies (e.g., Relatlimab (BMS-986016 / ONO-4482), LAG525, REGN3767, and MK-4280), LAG-3 fusion proteins (e.g., IMP321), anti-Tim3 antibodies (e.g., MBG453, TSR-022, and BMS-986258 / ONO-7807), and anti-KIR Antibodies (e.g., Lirilumab (BMS-986015 / ONO-4483), IPH2101, LY3321367, and MK-4280, etc.), anti-BTLA antibodies, anti-TIGIT antibodies (e.g., Tiragolumab (MTIG-7192A / RG-6058 / RO-7092284) and BMS-986207 (ONO-4686, etc.), TIGIT bispecific antibodies antibodies, anti-VISTA antibodies (e.g., JNJ-61610588, etc.), anti-CD137 antibodies (e.g., Urelumab (ONO-4481 / BMS-663513) and Utomilumab (PF-05082566), etc.), anti-CSF-1R antibodies / CSF-1R inhibitors (e.g., Cabiralizumab (FPA008 / BMS-986227 / ONO-4687)),Emactuzumab (RG7155 / RO5509554), LY3022855, MCS-110, IMC-CS4, AMG820, Pexidartinib, BLZ945, and ARRY-382, etc.), anti-OX40 antibodies (e.g., MEDI6469, PF-04518600, MEDI0562, MEDI6383, Efizonerimod, GSK3174998, BMS-986178, and MOXR0916, etc.), anti-HVEM antibodies, anti-CD27 antibodies (e.g., Varlilumab (CD X-1127, etc.), anti-GITR antibodies (e.g., MK-4166, INCAGN01876, GWN323, and TRX-518, etc.), anti-CD28 antibodies, anti-CCR4 antibodies (e.g., Mogamulizumab, etc.), anti-B7-H3 antibodies (e.g., Enoblituzumab, etc.), anti-ICOS agonist antibodies (e.g., JTX-2011 and GSK3359609, etc.), anti-CD4 antibodies (e.g., MTRX-1011A, TRX-1, Ibalizumab, huB-F5, Zanolimumab, 4162, etc.), W94, Clenoliximab, Keliximab, AD-519, PRO-542, Cedelizumab, TNX-355, Dacetuzumab, Tregalizumab, Priliximab, MDX-CD4, CAMPATH-9, and IT1208, etc.), anti-DEC-205 antibody / NY-ESO-1 fusion protein (e.g., CDX-1401, etc.), anti-SLAMF7 antibody (e.g., Elotuzumab, etc.), anti-CD73 antibody (e.g., Oleclumab and BMS-986179, etc.), ), anti-CD122 antibodies (e.g., NKTR-214, etc.), anti-CD40 agonist antibodies (e.g., ABBV-428, APX005M, and RO7009789, etc.), IDO inhibitors (e.g., Epacadostat, Indoximod, and BMS-986205, etc.), TLR agonists (e.g., Motolimod, CMP-001, G100, IMO-2125, SD-101, and MEDI9197, etc.), adenosine A2A receptor antagonists (e.g., Preladenant, AZD4635, PBF 509, and CPI-444, etc.), anti-NKG2A antibodies (e.g., Monalizumab, etc.), anti-CSF-1 antibodies (e.g., PD0360324, etc.), immune enhancers (e.g.,PV-10, etc.), IL-15 superagonists (e.g., ALT-803, etc.), soluble LAG3 (e.g., IMP321, etc.), CD47 antagonists (e.g., ALX148, etc.), anti-CD47 antibodies (e.g., ONO-7913, etc.), SIRPα fusion proteins (e.g., TTI-621, TTI-622, ALX148, etc.), anti-CCR8 antibodies, IL-12 antagonists (e.g., M9241, etc.), IL-12 fusion proteins, TGFβ receptor fusion proteins (e.g., BMS-986416, etc.), anti-ILT4 antibodies (e.g., MK-4830, etc.), EP4 antagonists (e.g., ONO-4578, etc.), STING agonists (e.g., ONO-7914, etc.), and T cell engagers (blinatumomab, BRiTE, etc.). Nivolumab can be produced according to the method described in WO2006 / 121168, pembrolizumab can be produced according to the method described in WO2008 / 156712, BMS-936559 can be produced according to the method described in WO2007 / 005874, and ipilimumab can be produced according to the method described in WO2001 / 014424.

[0433] Other antibody drugs include, for example, anti-IL-1β antibodies (such as canakinumab) and anti-CCR2 antibodies (such as plozalizumab).

[0434] In addition, other cancer treatments include radiation therapy, transarterial chemoembolization (TACE), transarterial embolization (TAE), cancer vaccines (e.g., synthetic peptides, DNA vaccines, and recombinant viruses), and immune cell therapy (e.g., dendritic cells, CAR-T cells, etc.). [Prescription] When the compounds of the present invention or combinations of the compounds of the present invention with other drugs are used for the above purposes, they are usually administered systemically or locally, orally or parenterally. The dosage varies depending on age, body weight, symptoms, therapeutic effect, administration method, treatment time, etc., but is usually administered orally in the range of 1 ng to 2,000 mg per adult once or several times a day, or parenterally in the range of 0.1 ng to 200 mg per adult once or several times a day, or by continuous intravenous administration for 30 minutes to 24 hours a day. Of course, as mentioned above, the dosage varies depending on various conditions, so a smaller dosage than the above may be sufficient, or a dosage exceeding the range may be necessary. [formulation] When the compound of the present invention, etc., or a combination of the compound of the present invention and another drug is administered, it is used as a solid or liquid preparation for oral administration, a sustained-release preparation or a controlled-release preparation for oral administration, or an injection, infusion, external preparation, inhalant, suppository, etc. for parenteral administration.

[0435] Examples of solid preparations for oral administration include tablets, pills, capsules, powders, and granules, and examples of capsules include hard capsules and soft capsules.

[0436] The solid preparation may be prepared by, for example, combining the compound of the present invention with a pharmaceutically acceptable carrier. Examples of the pharmaceutically acceptable carrier used in the preparation of the solid preparation include excipients (e.g., lactose, mannitol, glucose, microcrystalline cellulose, and starch), binders (e.g., hydroxypropyl cellulose, polyvinylpyrrolidone, and magnesium aluminometasilicate), disintegrants (e.g., calcium cellulose glycolate), lubricants (e.g., magnesium stearate), stabilizers, and solubilizers (e.g., glutamic acid, aspartic acid). If necessary, the solid preparation may be coated with a coating agent (e.g., sucrose, gelatin, hydroxypropyl cellulose, and hydroxypropylmethylcellulose phthalate), or may be coated with two or more layers. Furthermore, the solid preparation may be contained in a capsule containing gelatin.

[0437] Liquid preparations for oral administration may be in any form, such as a solution, suspension, emulsion, syrup, or elixir, and may be formulated by dissolving, suspending, or emulsifying the compound of the present invention in a diluent (e.g., purified water, ethanol, or a mixture thereof). Furthermore, the liquid preparation may contain a wetting agent, a suspending agent, an emulsifier, a sweetener, a flavoring agent, an aromatic agent, a preservative, or a buffer.

[0438] The sustained-release preparation for oral administration may contain, for example, a gel-forming substance, and examples of the gel-forming substance include gum arabic, agar, polyvinylpyrrolidone, sodium alginate, propylene glycol alginate, carboxyvinyl polymer, carboxymethylcellulose, sodium carboxymethylcellulose, guar gum, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, methylcellulose, and hydroxyethylmethylcellulose.

[0439] Injections or infusions for parenteral administration may be in the form of any of aqueous solutions, suspensions, or emulsions, or may be formulated as solid preparations together with a pharmaceutically acceptable carrier so that they can be dissolved, suspended, or emulsified by adding a solvent (e.g., distilled water for injection, physiological saline, glucose solution, and isotonic solutions (e.g., solutions of sodium chloride, potassium chloride, glycerin, mannitol, sorbitol, boric acid, borax, propylene glycol, etc.)) when used. Here, examples of the "pharmaceutically acceptable carrier" include stabilizers (e.g., various amino acids, albumin, globulin, gelatin, mannitol, glucose, dextran, ethylene glycol, propylene glycol, polyethylene glycol, ascorbic acid, sodium bisulfite, sodium thiosulfate, sodium edetate, sodium citrate, and dibutylhydroxytoluene), solubilizing agents (e.g., alcohols (e.g., ethanol), polyalcohols (e.g., propylene glycol, polyethylene glycol), and nonionic surfactants (e.g., Polysorbate 20 (registered trademark), Polysorbate 80 (registered trademark), and HCO-50), etc.), suspending agents (e.g., glyceryl monostearate, aluminum monostearate, methylcellulose, carboxymethylcellulose, hydroxymethylcellulose, and sodium lauryl sulfate, etc.), emulsifiers (e.g., gum arabic, sodium alginate, tragacanth, etc.), soothing agents (e.g., benzyl alcohol, chlorobutanol, sorbitol, etc.), buffers (e.g., phosphate buffer, acetate buffer, borate buffer, carbonate buffer, citrate buffer, Tris buffer, glutamate buffer, epsilon aminocaproic acid buffer, etc.), preservatives (e.g., methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, chlorobutanol, benzyl alcohol, benzalkonium chloride, sodium dehydroacetate, sodium edetate, boric acid, borax, etc.), antiseptics (e.g., benzalkonium chloride, parahydroxybenzoic acid, chlorobutanol, etc.), pH adjusters (e.g., hydrochloric acid, sodium hydroxide, phosphoric acid, acetic acid, etc.), and antioxidants.Examples of antioxidants that can be used include: (1) water-soluble antioxidants such as ascorbic acid, cysteine ​​hydrochloride, sodium bisulfate, sodium metabisulfite, and sodium sulfite; (2) oil-soluble antioxidants such as ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, lecithin, propyl gallate, and α-tocopherol; and (3) metal chelating agents such as citric acid, ethylenediaminetetraacetic acid, sorbitol, tartaric acid, and phosphoric acid.

[0440] The injection or infusion solution can be produced by sterilizing it in the final step or by an aseptic procedure, for example, by sterilizing it by filtration with a filter or the like, and then filling it into a sterile container. Alternatively, the injection or infusion solution can be used by dissolving a sterile powder (which may contain a powder of a pharmaceutically acceptable carrier) obtained by vacuum drying or freeze-drying in an appropriate solvent just before use.

[0441] Dosage forms of external preparations for parenteral administration include, for example, aerosols, inhalants, sprays, ointments, gels, creams, poultices, patches, liniments, and nasal drops.

[0442] The propellants, inhalants and sprays may contain, in addition to commonly used diluents, stabilizers such as sodium bisulfite and buffers that provide isotonicity, such as sodium chloride, sodium citrate or citric acid. The manufacturing methods for sprays are described in detail in, for example, U.S. Patent Nos. 2,868,691 and 3,095,355.

[0443] The inhalant may be a liquid or powder for inhalation, and the liquid may be dissolved or suspended in water or other suitable medium before use. These inhalants are produced according to known methods. For example, in the case of a liquid for inhalation, preservatives (e.g., benzalkonium chloride and parabens, etc.), colorants, buffers (e.g., sodium phosphate and sodium acetate, etc.), isotonicity agents (e.g., sodium chloride and concentrated glycerin, etc.), thickeners (e.g., carboxyvinyl polymers, etc.), and absorption enhancers, etc. are mixed as needed. On the other hand, in the case of powder for inhalation, lubricants (e.g., stearic acid and its salts, etc.), binders (e.g., starch and dextrin, etc.), excipients (e.g., lactose and cellulose, etc.), colorants, preservatives (e.g., benzalkonium chloride and parabens, etc.), and absorption enhancers, etc. are mixed as needed. When administering liquid preparations for inhalation, sprayers (such as atomizers and nebulizers) are usually used, while when administering powder preparations for inhalation, inhalation administerers for powder preparations are usually used.

[0444] The ointment is prepared by a known or commonly used formulation, for example, by mixing or dissolving the compound of the present invention in an ointment base. Here, the ointment base is selected from known or commonly used ones, and examples thereof include higher fatty acids or higher fatty acid esters (e.g., adipic acid, myristic acid, palmitic acid, stearic acid, oleic acid, adipate esters, myristic acid esters, palmitate esters, stearates, oleate esters, etc.), waxes (e.g., beeswax, spermaceti, ceresin, etc.), surfactants (e.g., polyoxyethylene alkyl ether phosphate esters, etc.), higher alcohols (e.g., cetanol, stearyl alcohol, cetosterol, etc.), and the like. These agents are used by mixing one or more selected from the group consisting of: allyl alcohol, silicone oils (e.g., dimethylpolysiloxane, etc.), hydrocarbons (e.g., hydrophilic petrolatum, white petrolatum, refined lanolin, and liquid paraffin, etc.), glycols (e.g., ethylene glycol, diethylene glycol, propylene glycol, polyethylene glycol, and macrogol, etc.), vegetable oils (e.g., castor oil, olive oil, sesame oil, and turpentine oil, etc.), animal oils (e.g., mink oil, egg yolk oil, squalane, and squalene, etc.), water, absorption enhancers, and anti-rash agents. They may also contain moisturizers, preservatives, stabilizers, antioxidants, and fragrances.

[0445] The gel is prepared by a known or commonly used method, for example, by dissolving the compound of the present invention in a gel base. Here, the gel base is selected from known or commonly used ones, and is used by mixing one or more selected from lower alcohols (e.g., ethanol and isopropyl alcohol), gelling agents (e.g., carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, and ethylcellulose), neutralizing agents (e.g., triethanolamine and diisopropanolamine), surfactants (e.g., polyethylene glycol monostearate), gums, water, absorption enhancers, and anti-rash agents. In addition, the gel may contain preservatives, antioxidants, flavoring agents, etc.

[0446] Creams are prepared according to known or commonly used formulations, for example, by dissolving or emulsifying the compound of the present invention in a cream base. The cream base is selected from known or commonly used bases, and may be a mixture of one or more of higher fatty acid esters, lower alcohols, hydrocarbons, polyhydric alcohols (e.g., propylene glycol and 1,3-butylene glycol), higher alcohols (e.g., 2-hexyldecanol and cetanol), emulsifiers (e.g., polyoxyethylene alkyl ethers and fatty acid esters), water, absorption enhancers, and anti-rash agents. The cream base may further contain preservatives, antioxidants, flavoring agents, etc.

[0447] The poultice can be prepared by a known or commonly used method, for example, by dissolving the compound of the present invention in a poultice base, kneading the mixture, and spreading it on a support. Here, the poultice base can be selected from known or commonly used poultice bases, and can be used by mixing one or more selected from thickeners (e.g., polyacrylic acid, polyvinylpyrrolidone, gum arabic, starch, gelatin, methylcellulose, etc.), humectants (e.g., urea, glycerin, propylene glycol, etc.), fillers (e.g., kaolin, zinc oxide, talc, calcium, magnesium, etc.), water, solubilizers, tackifiers, and anti-rash agents. It may further contain preservatives, antioxidants, flavoring agents, etc.

[0448] The patch is prepared by a known or commonly used method, for example, by dissolving the compound of the present invention in a patch base and spreading the resulting mixture on a support. The patch base is selected from known or commonly used bases, and may be a mixture of one or more selected from polymer bases, oils and fats, higher fatty acids, tackifiers, and anti-rash agents. It may further contain a preservative, antioxidant, flavoring agent, etc.

[0449] The liniment is prepared by a known or commonly used formulation, for example, by dissolving, suspending or emulsifying the compound of the present invention in one or more selected from water, alcohol (e.g., ethanol, polyethylene glycol, etc.), higher fatty acid, glycerin, soap, emulsifier, suspending agent, etc. It may further contain a preservative, antioxidant, flavoring agent, etc.

[0450] Unless otherwise defined, all technical and scientific terms and abbreviations used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0451] In one aspect, the present invention provides the following embodiment. [1] General formula (I)

[0452] [ka]

[0453] (In the formula, R 1 (1) 1 to 5 R 11 (2) methylene substituted with a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 12 (3) methylene substituted with a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R 13 (4) methylene substituted with a C2-4 alkenyl group optionally substituted with 1 to 5 R 14 represents a methylene substituted by a C2-4 alkynyl group which may be substituted by R 11 , R 12 , R 13 and R 14 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, or (6) a cyano group; 11 , R 12 , R 13 and R 14may be the same or different, R 2 (1) 1 to 5 R 15 (2) a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R 16 or (3) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 17 represents a C1-4 alkyl group optionally substituted with R 15 , R 16 and R 17 are each independently (1) 1 to 5 R 18 (1) a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with (C1-8 alkyl)carbonyl group; (2) a (C1-8 alkyl)carbonyl group; (3) 1 to 5 R 19 (4) a C1-8 haloalkyl group, (5) a 5- or 6-membered carbocyclic ring, (6) a 5- or 6-membered heterocyclic ring, (7) a C1-4 alkylsulfonyl group, (8) a C2-4 alkenylsulfonyl group, (9) a C1-4 alkoxycarbonyl group, (10) a C1-4 haloalkylamino group, (11) a t-butyloxycarbonylamino group, or (12) a 5,5-dimethyl-2,4-dioxooxazolidin-3-yl group; Multiple R 15 , R 16 and R 17 may be the same or different, R 18 and R 19 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, or (6) a cyano group; Multiple R 18 and R 19 may be the same or different, R 3 is (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, (6) a C1-4 haloalkoxy group, (7) a cyano group, or (8) 1 to 5 R 20(9) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 21 a 3- to 15-membered heterocycle optionally substituted with (10)-NR 22 R 23 , (11)-OR 24 , (12)-CONR 25 R 26 (13) a (C1-8 alkyl)carbonyl group, (14) a C1-4 alkyl group substituted with a hydroxyl group, or (15) a 1-(hydroxyimino)ethyl group; R 20 and R 21 are each independently: (1) 1 to 5 R 27 (1) a C1-4 alkyl group optionally substituted with (1-5), (2) a halogen atom, (3) 1 to 5 R 28 (4) a C cycloalkyl group optionally substituted with 1 to 5 R 27-1 (5) a C1-4 alkoxy group optionally substituted with (4), (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R 20 and R 21 may be the same or different, R 27 , R 27-1 and R 28 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R 27 , R 27-1 and R 28 may be the same or different, R 22 , R 23 and R 24 are each independently (1) a hydrogen atom, (2) 1 to 5 R 29 (3) a C alkyl group optionally substituted with 1 to 5 R 29-1 (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2(5) a C2-4 alkynyl group optionally substituted with 1 to 5 R 30 or (6) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 31 represents a 3- to 15-membered heterocycle optionally substituted by R 29 , R 29-1 , R 29-2 , R 30 and R 31 are each independently (1) 1 to 5 R 32 (1) a C1-4 alkyl group optionally substituted with (1-5), (2) a halogen atom, (3) 1 to 5 R 33 (4) a C cycloalkyl group optionally substituted with 1 to 5 R 34 (5) a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R 35 (6) a 5- to 6-membered heterocycle optionally substituted with 1 to 5 R 32-1 (7) a C1-4 alkoxy group optionally substituted with (4), (8) a hydroxyl group, (9) a carbamoyl group, or (10) a cyano group; Multiple R 29 , R 29-1 , R 29-2 , R 30 and R 31 may be the same or different, R 32 , R 32-1 , R 33 , R 34 and R 35 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R 32 , R 32-1 , R 33 , R 34 and R 35 may be the same or different, R 25 and R 26are each independently (1) a hydrogen atom, (2) 1 to 5 R 36 (3) a C alkyl group optionally substituted with 1 to 5 R 36-1 (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 36-2 (5) a C2-4 alkynyl group optionally substituted with 1 to 5 R 37 or (6) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R 38 represents a 3- to 15-membered heterocycle optionally substituted by R 36 , R 36-1 , R 36-2 , R 37 and R 38 each independently represents (1) a C1-4 alkyl group, (2) a halogen, (3) a C3-8 cycloalkyl group, (4) a 5- or 6-membered carbocyclic ring, (5) a 5- or 6-membered heterocyclic ring, (6) a C1-4 alkoxy group, (7) a C1-4 haloalkyl group, (8) a C1-4 haloalkoxy group, (9) a hydroxyl group, (10) a carboxyl group, (11) a carbamoyl group, or (12) a cyano group; Multiple R 36 , R 36-1 , R 36-2 , R 37 and R 38 may be the same or different, R 4 represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; R 5 represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; X is a nitrogen atom or CR 7 represents X 1 , X 2 , and X 3 are each independently a nitrogen atom, CH, or CR 6 represents R 6 represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; R 6 If there are multiple R 6 may be the same or different, Y 1 is a nitrogen atom, or CR 8 represents Y 2 is a nitrogen atom, or CR 9 represents Y 3 is a nitrogen atom, or CR 10 represents R 7 represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R 8 represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R 9 represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R 10 is (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, (6) a C1-4 haloalkoxy group, (7) a hydroxyl group, (8) an amino group, (9) a carboxyl group, (10) a carbamoyl group, (11) a (C1-4 alkyl)aminocarbonyl group, (12) a di-(C1-4 alkyl)aminocarbonyl group, (13) -CO- (a 3- to 6-membered saturated heterocycle), or (14) -CONHR 39 or (15) a cyano group; R 39is (1) a C1-4 alkyl group substituted with a cyano group, (2) a C1-4 alkoxy group, (3) a C1-4 haloalkyl group, (4) a C1-4 haloalkoxy group, (5) a hydroxyl group, (6) an amino group, (7) a (C1-4 alkyl)amino group, (8) a di-(C1-4 alkyl)amino group, or (9) 1 to 5 R 40 or (10) 1 to 5 R 41 represents a 3- to 6-membered saturated heterocycle optionally substituted by R 40 and R 41 each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, or (5) a C1-4 haloalkoxy group; Multiple R 40 and R 41 may be the same or different, r represents an integer of 0 to 3, and a plurality of R 4 may be the same or different, s represents an integer of 0 to 3, and a plurality of R 5 may be the same or different. wherein each hydrogen atom may be a deuterium atom or a tritium atom.) or a salt thereof; [2] General formula (I-1)

[0454] [ka]

[0455] (wherein t represents an integer of 0 to 3, and other symbols have the same meanings as in [1]), or a salt thereof; [3] R 2 However, 1 to 5 R 15 the compound according to [1] or [2], or a salt thereof, wherein the compound is a 5- to 7-membered nitrogen-containing saturated heterocycle optionally substituted by [4] R 1 However, 1 to 5 R 11the compound according to any one of [1] to [3], or a salt thereof, wherein methylene is substituted with a 5- or 6-membered carbocyclic ring optionally substituted with [5] R 3 However, (1) each has 1 to 5 R 20 (2) a 5- to 6-membered carbocyclic ring or indan, optionally substituted with 1 to 5 R 21 or (3) -NR 22 R 23 the compound according to any one of [1] to [4], or a salt thereof; [6] General formula (I-1-1)

[0456] [ka]

[0457] (In the formula, R 1-1 is 1 to 5 R 11 ring 1 represents a 5- to 7-membered nitrogen-containing saturated heterocycle; R 3-1 (1) 1 to 5 R 20 (2) a 5- to 6-membered carbocyclic ring or indan, optionally substituted with 1 to 5 R 21 or (3) -NR 22 R 23 represents R 15-1 is 1 to 5 R 18 a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted by, or a C1-8 haloalkyl group, u represents an integer of 0 to 2, and other symbols have the same meaning as in [1].), or a salt thereof according to any one of [1] to [5]; [7] General formula (I-1-1-1)

[0458] [ka]

[0459] (Wherein, ring 2 is (1) each of 1 to 5 R 20 (2) a 5- to 6-membered carbocyclic ring or indane, optionally substituted with 1 to 5 R 21 and the other symbols have the same meanings as in [1] and [6].) or a salt thereof; [8] The compound is (1) 1-(3-{7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)cyclopropanecarboxylic acid, (2) 2-(3-{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)-2-methylpropanoic acid, or (3) The compound according to [7], which is 4-({7-[(5-{9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-2-[2-methyl-4-(trifluoromethoxy)phenyl]-8-oxo-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)-3-fluorobenzonitrile, or a salt thereof; [9] General formula (I-1-1-2)

[0460] [ka]

[0461] (wherein ring 3 is a group having 1 to 5 R 30a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R 31 represents a 5- to 6-membered heterocycle optionally substituted by 23-1 is (1) a hydrogen atom, (2) 1 to 5 R 29 (3) a C alkyl group optionally substituted with 1 to 5 R 29-1 or (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R 29-2 and the other symbols have the same meanings as in [1] and [6].) or a salt thereof;

[10] The compound is (1) 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-{[4-(difluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one, (2) 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, (3) 9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7-(6-{[9-(2-fluoro-4-methylbenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-6-methyl-2-{[4-(trifluoromethoxy)phenyl]amino}-7,9-dihydro-8H-purin-8-one, (4) 4-[(7-{[5-(9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, (5) 3-fluoro-4-({7-[(5-{2-[(3-fluorophenyl)amino]-6-methyl-8-oxo-9-(1-{[1-(trifluoromethyl)cyclopropyl]methyl}-4-piperidinyl)-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile, (6) 4-[(7-{[5-(2-{[2-chloro-4-(trifluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, or (7) The compound according to [9], which is 7-(6-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, or a salt thereof;

[11] General formula (I-1-1-3)

[0462] [ka]

[0463] (wherein all symbols have the same meaning as in [1], [6] and [9]), or a salt thereof;

[12] The compound according to

[11] , wherein the compound is (1) 1-{[{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}(cyclohexyl)amino]methyl}cyclobutanecarboxylic acid, or a salt thereof;

[13] A pharmaceutical composition containing the compound represented by formula (I) or a salt thereof according to [1]; [13-1] The pharmaceutical composition according to

[13] , further comprising a pharmaceutically acceptable carrier;

[14] The pharmaceutical composition according to

[13] , which is a DGKα and / or DGKζ inhibitor;

[15] The pharmaceutical composition according to

[13] or

[14] , which is an agent for inhibiting the progression, inhibiting recurrence, and / or treating a DGKα- and / or DGKζ-associated disease;

[16] The pharmaceutical composition according to

[15] , wherein the DGKα and / or DGKζ-associated disease is cancer or an infectious disease;

[17] The pharmaceutical composition according to

[16] , wherein the cancer is a solid cancer or a blood cancer;

[18] The pharmaceutical composition according to

[17] , wherein the solid cancer is one or more cancers selected from malignant melanoma, non-small cell lung cancer, small cell lung cancer, head and neck cancer, renal cell carcinoma, breast cancer, ovarian cancer, ovarian clear cell adenocarcinoma, nasopharyngeal carcinoma, uterine cancer, anal cancer, colorectal cancer, rectal cancer, colon cancer, hepatocellular carcinoma, esophageal cancer, gastric cancer, esophagogastric junction cancer, pancreatic cancer, urothelial carcinoma, prostate cancer, fallopian tube cancer, primary peritoneal cancer, malignant pleural mesothelioma, gallbladder cancer, bile duct cancer, biliary tract cancer, skin cancer, testicular cancer (germ cell tumor), vaginal cancer, vulvar cancer, penile cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, spinal tumor, neuroblastoma, medulloblastoma, ocular retinoblastoma, neuroendocrine tumor, brain tumor, and squamous cell carcinoma;

[19] The pharmaceutical composition according to

[17] , wherein the solid cancer is bone and soft tissue sarcoma or Kaposi's sarcoma;

[20] The pharmaceutical composition according to

[17] , wherein the blood cancer is one or more cancers selected from multiple myeloma, malignant lymphoma, leukemia, myelodysplastic syndrome, and myeloproliferative syndrome;

[21] An agent for inhibiting the progression, inhibiting recurrence and / or treating a DGKα and / or DGKζ-associated disease, comprising the compound represented by general formula (I) according to [1] or a salt thereof;

[22] A method for inhibiting the progression, inhibiting recurrence, and / or treating a DGKα and / or DGKζ-associated disease, comprising administering an effective amount of the compound represented by general formula (I) according to [1] or a salt thereof to a mammal;

[23] A compound represented by formula (I) according to [1] or a salt thereof, used for inhibiting the progression, inhibiting recurrence and / or treating a DGKα and / or DGKζ-associated disease; and

[24] Use of a compound represented by general formula (I) according to [1] or a salt thereof for the manufacture of an agent for inhibiting the progression, inhibiting recurrence and / or treating a disease associated with DGKα and / or DGKζ.

[0464] The contents of all patent and non-patent literature or references explicitly cited in this specification are hereby incorporated by reference in their entirety.

[0465] The present invention will be described in more detail by the following examples, but the scope of the present invention is not limited thereto. Various changes or modifications can be made by those skilled in the art based on the description of the present invention, and these changes or modifications are also included in the present invention. [Example] The present invention will be described in detail below with reference to examples and biological examples, but the present invention is not limited to these.

[0466] The solvents in parentheses shown in the chromatographic separations and TLC charts indicate the elution or development solvents used, and the ratios are by volume. The medium-pressure preparative cartridge column used was a Chromatorex Q-PACK SI or NH (Fuji Silysia Chemical), and the inject column was silica gel or amino (Yamazen). Reverse-phase HPLC column purification was performed under the following conditions: Column: YMC Triart C 18 30 mm x 75 mm, 5 μm; Flow rate: 40 mL / min; Mobile phase A: 0.1% trifluoroacetic acid (TFA) in water; Mobile phase B: 0.1% TFA in acetonitrile; Gradient (ratio of mobile phase (A):mobile phase (B) is listed): 0-0.50 min: (90%:10%); 0.50-9.00 min: (90%:10%) to (20%:80%); 9.01-11.00 min: (0%:100%) LCMS was carried out using a Shimadzu Nexera X2 (A) or Waters i-class (B) system under the following conditions. Column: YMC Triart C 18 2.0 mm × 30 mm, 1.9 μm; Flow rate: 1.0 mL / min; Temperature: 30 °C; Mobile phase A: 0.1% TFA in water; Mobile phase B: 0.1% TFA in acetonitrile; Gradient (ratio of mobile phase (A) to mobile phase (B) is given): 0 to 0.10 min: (95%:5%); 0.10 to 1.20 min: (95%:5%) to (5%:95%); 1.20 to 1.50 min: (5%:95%).

[0467] The values ​​shown in the NMR section are those obtained when the measurement solvent shown in parentheses was used. 1 These are H-NMR measurements (chemical shift values).

[0468] The names of compounds used in this specification were generally generated using computer programs that perform naming according to IUPAC rules, such as ACD / Name (registered trademark) (version 6.00, manufactured by Advanced Chemistry Development Inc.), Chemdraw Ultra (version 12.0, manufactured by Cambridge Soft), or Lexichem Toolkit (version 1.4.2, manufactured by OpenEye Scientific Software), or were generated according to IUPAC nomenclature. Reference example 1 2-Methyl-2-propanyl 9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate 2-Methyl-2-propanyl 5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate (CAS: 1354801-07-2, 4.0 g) and 1-(bromomethyl)-2,4-difluorobenzene (2.1 mL) were dissolved in dimethylformamide (DMF) (40 mL). The reaction mixture was ice-cooled, and sodium hydride (60% suspension in paraffin oil, 703 mg) was added and stirred for 40 minutes. Saturated aqueous ammonium chloride was added to the reaction mixture, followed by stirring and extraction with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 4:1) to give the title compound (5.1 g) with the following physical properties. TLC: Rf 0.42 (hexane:ethyl acetate=4:1); 1 H-NMR (CDCl3): δ 1.47, 2.79, 3.74, 4.53, 5.45, 6.73, 6.77-7.04, 7.08, 7.80, 8.29. Reference example 2 9-(2,4-Difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine dihydrochloride The compound (5.1 g) prepared in Reference Example 1 was dissolved in methanol (10 mL), and a 4N hydrogen chloride / 1,4-dioxane solution (32 mL) was added, followed by stirring at room temperature for 40 minutes. The reaction mixture was concentrated and azeotroped with toluene. The resulting residue was filtered using 2-methoxy-2-methylpropane (hereinafter sometimes abbreviated as MTBE) to give the title compound (4.6 g) having the following physical properties: TLC: Rf 0.37 (dichloromethane:methanol=9:1); 1 H-NMR (DMSO-d6): δ 2.98, 3.43, 4.35, 5.53, 6.97-7.03, 7.06, 7.13-7.33, 8.03, 8.29, 9.94. Reference example 3 2-Methyl-2-propanyl 4-[(5-amino-2-chloro-6-methyl-4-pyrimidinyl)amino]-1-piperidinecarboxylate N-ethyl-N-isopropyl-2-propanamine (hereinafter sometimes abbreviated as DIPEA) (4.7 mL) was added to 2-methyl-2-propanyl 4-amino-1-piperidinecarboxylate (2.6 g) and 2,4-dichloro-6-methyl-5-pyrimidinamine (2.2 g), and the mixture was stirred at 100 °C overnight. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 3:1 → 1:4) to give the title compound (2.8 g) with the following physical properties. LC-MS(A) retention time (min): 1.11; MS(ESI, Pos.): 342 (M + H) + ; 1 H-NMR (DMSO-d6): δ 1.24-1.37, 1.39-1.42, 1.82-1.91, 2.12, 2.80-3.00, 3.85-4.06, 4.66, 6.51. Reference example 4 2-Methyl-2-propanyl 4-[(2-chloro-5-{[4-(methoxycarbonyl)phenyl]amino}-6-methyl-4-pyrimidinyl)amino]-1-piperidinecarboxylate The compound prepared in Reference Example 3 (5.0 g) and methyl 4-iodobenzoate (4.6 g) were dissolved in anhydrous 1,2-dimethoxyethane (hereinafter, sometimes abbreviated as DME) (50 mL). To the solution were added cesium carbonate (7.1 g), (9,9)-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (hereinafter, sometimes abbreviated as Xantphos) (510 mg), and (1E,4E)-1,5-diphenyl-1,4-pentadiene-3-one-palladium complex (3:2) (hereinafter, sometimes abbreviated as Pd2(dba)3) (400 mg). The atmosphere in the reaction vessel was replaced with nitrogen, and the mixture was stirred at 80°C for 4 hours. The reaction mixture was diluted with DME (100 mL), stirred at 80°C for 15 minutes, and then filtered through Celite (trade name) to remove insoluble matter. The filtrate was concentrated, and to the resulting residue was added a mixture of hexane and ethyl acetate (2:1) (60 mL), followed by stirring and filtering to obtain the title compound (6.6 g) having the following physical properties: LC-MS(A) retention time (min): 1.14; MS(ESI, Pos.): 476 (M + H) + ; 1 H-NMR(CDCl3):δ 1.18-1.35, 1.43, 1.89-1.98, 2.22, 2.90, 3.83-3.91, 3.95-4.20, 5.09, 5.23, 6.51-6.57, 7.88-7.94. Reference example 5 2-Methyl-2-propanyl 4-{2-chloro-7-[4-(methoxycarbonyl)phenyl]-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl}-1-piperidinecarboxylate The compound prepared in Reference Example 4 (1.7 g) was dissolved in tetrahydrofuran (hereinafter sometimes abbreviated as THF) (17 mL), and di-1H-imidazol-1-ylmethanone (hereinafter sometimes abbreviated as CDI) (1.2 g) and 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine (hereinafter sometimes abbreviated as DBU) (540 mg) were added and stirred at room temperature for 2 hours. The reaction solution was diluted with ethyl acetate and washed successively with water, 0.1 N hydrochloric acid, and saturated brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound (1.8 g) having the following physical properties: TLC: Rf 0.54 (hexane:ethyl acetate=1:1); 1 H-NMR(CDCl3): δ 1.50, 1.76-1.86, 2.09, 2.59, 2.76-2.93, 3.97, 4.23-4.61, 4.52-4.63, 7.45-7.52, 8.20-8.25. Reference example 6 4-[2-chloro-6-methyl-9-(1-{[(2-methyl-2-propanyl)oxy]carbonyl}-4-piperidinyl)-8-oxo-8,9-dihydro-7H-purin-7-yl]benzoic acid The compound prepared in Reference Example 5 (469 mg) was dissolved in THF (18 mL) and cooled to 0°C. Potassium trimethylsilanolate (hereinafter sometimes abbreviated as TMSOK) (239 mg) was added thereto and stirred at room temperature for 3 hours. 1N hydrochloric acid was added to the reaction solution to adjust the pH to 2, and the solution was extracted with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (450 mg) having the following physical properties: LC-MS(A) retention time (min): 1.15; MS(ESI, Pos.): 488 (M + H) + ; 1 H-NMR(CDCl3): δ 1.50, 1.76-1.86, 2.11, 2.48-2.66, 2.74-2.95, 4.24-4.44, 4.52-4.62, 7.49-7.53, 8.26-8.31. Reference example 7 2-Methyl-2-propanyl 4-[2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate The compound prepared in Reference Example 2 (536 mg) and the compound prepared in Reference Example 6 (650 mg) were dissolved in DMF (13 mL), DIPEA (0.69 mL) and (dimethylamino)-N,N-dimethyl(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yloxy)methaniminium hexafluorophosphate (hereinafter sometimes abbreviated as HATU) (658 mg) were added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water and extracted with a hexane:ethyl acetate mixture (3:7). The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 2:1 → 0:1) to give the title compound (1.0 g) with the following physical properties. LC-MS(A) retention time (min): 1.27; MS(ESI, Pos.): 769 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.44, 1.82, 2.25-2.40, 2.79-3.00, 3.60-4.16, 4.51, 4.59-4.91, 5.22-5.61, 6.84-7.08, 7.09-7.38, 7.65, 7.93, 8.24. Reference example 8 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-9-(4-piperidinyl)-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 7 (450 mg) was dissolved in methanol (4.5 mL), and a 4N hydrogen chloride / 1,4-dioxane solution (2.9 mL) was added and stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was dissolved in methanol and passed through an inject column (Amino (trade name)). The resulting filtrate was concentrated to give the title compound (390 mg) having the following physical properties: LC-MS(A) retention time (min): 0.96; MS(ESI, Pos.): 669 (M + H) + . Reference example 9 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 8 (390 mg) was dissolved in DMF (7.8 mL), and pivalaldehyde (0.32 mL), acetic acid (0.33 mL), and sodium triacetoxyborohydride (618 mg) were added, followed by stirring at room temperature for 4 hours. The reaction mixture was ice-cooled, and saturated aqueous sodium bicarbonate solution was added. After extraction with ethyl acetate, the organic layer was washed with water and concentrated through an inject column (Amino (trade name)) to obtain the title compound (406 mg) having the following physical properties. LC-MS(A) retention time (min): 1.06; MS(ESI, Pos.): 739 (M + H) + . Example 1 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 9 (390 mg) was dissolved in toluene (2.5 mL), and aniline (94 mg), cesium carbonate (330 mg), Xantphos (44 mg), and palladium acetate (11 mg) were added. The mixture was stirred at 100°C for 1 hour under a nitrogen atmosphere. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed twice with water and with saturated brine. After drying over anhydrous sodium sulfate, the organic layer was concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate = 3:1 → 1:2) to give the title compound (315 mg) having the following physical properties. LC-MS(A) retention time (min): 1.04; MS(ESI, Pos.): 796 (M + H) + ; 1 H-NMR(CDCl3):δ 0.95, 1.66-1.81, 1.99-2.07, 2.14, 2.38-2.53, 2.73-3.05, 3.69-4.16, 4.28-4.45, 4.55-4.95, 5.14-5.65, 6.66-7.06, 7.07-7.15, 7.33-7.40, 7.41-7.67, 7.67-7.74, 7.78-7.87, 8.32. Example 2 2-Cyclopentyl-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate The compound prepared in Reference Example 9 (20 mg) was dissolved in THF (0.2 mL), and bromo(cyclopentyl)zinc (0.3 mL, 0.5 mol / L, THF solution) and palladium-tris(2-methyl-2-propanyl)phosphine (1:2) (2.8 mg) were added, followed by stirring at 100°C for 2 hours under a nitrogen atmosphere. The reaction solution was ice-cooled, and saturated aqueous ammonium chloride solution was added, followed by extraction with ethyl acetate. The organic layer was concentrated, and the resulting residue was purified using a reverse-phase HPLC column to give the title compound (11 mg) having the following physical properties. LC-MS(A) retention time (min): 1.06; MS(ESI, Pos.): 773 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.02-1.16, 1.60-1.74, 1.74-1.85, 1.85-2.14, 2.81-3.07, 3.19-3.29, 3.62-3.73, 4.62-4.93, 5.19-5.62, 6.82-7.40, 7.45-7.81, 7.90-8.01, 8.19-8.31, 8.69-8.84, 8.92-9.02. Example 3 1-{7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}-3-piperidinecarboxylic acid 2-trifluoroacetate Dimethyl sulfoxide (hereinafter sometimes abbreviated as DMSO) (0.3 mL) was added to the compound (15 mg) prepared in Reference Example 9, and then 3-piperidinecarboxylic acid (6.6 mg), cesium fluoride (7.7 mg), and DIPEA (0.035 mL) were added and stirred for 15 hours at 100° C. Insoluble matter was filtered off with a cotton plug, and the filtrate was purified by reverse-phase HPLC column to give the title compound (15 mg) having the following physical properties. LC-MS(A) retention time (min): 1.03; MS(ESI, Pos.): 832 (M + H) + ; 1H-NMR(DMSO-d6):δ 1.03-1.13, 1.40-1.57, 1.57-1.77, 1.77-2.09, 2.36-2.46, 2.82-2.97, 3.01-3.14, 3.15-3.27, 3.31-3.35, 3.59-3.73, 3.96-4.07, 4.20-4.29, 4.44-4.55, 4.55-4.80, 4.81-4.90, 5.18-5.60, 6.85-7.22, 7.28-7.40, 7.44-7.76, 7.90-7.98, 8.12-8.31, 8.46-8.78, 8.86-9.05. Reference example 10 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one Using 2-methyl-2-propanyl (3S)-3-amino-1-piperidinecarboxylate instead of 2-methyl-2-propanyl 4-amino-1-piperidinecarboxylate used in Reference Example 3, the same procedures as in Reference Example 3 → Reference Example 4 → Reference Example 5 → Reference Example 6 → Reference Example 7 → Reference Example 8 → Reference Example 9 were carried out to obtain the title compound having the following physical properties. TLC: Rf 0.28 (hexane:ethyl acetate=1:1); 1 H-NMR (CDCl3):δ 0.87, 1.72-1.82, 1.83-1.95, 2.06-2.22, 2.31-2.43, 2.77-2.95, 3.17, 3.69-4.17, 4.54-4.93, 5.21-5.59, 6.68-6.79, 6.85, 6.91-7.06, 7.11, 7.37-7.70, 7.82, 8.32. Example 4 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one The same procedure as in Example 1 was carried out using the compound prepared in Reference Example 10 instead of the compound prepared in Reference Example 9 to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.13; MS(ESI, Pos.): 796 (M + H) + ; 1H-NMR(CDCl3):δ 0.89, 1.73-1.83, 1.83-1.94, 2.04, 2.09-2.21, 2.33-2.53, 2.81-2.97, 3.23, 3.69-4.10, 4.56-4.92, 5.22-5.59, 6.68-6.79, 6.81-6.97, 6.97-7.13, 7.30-7.38, 7.45-7.67, 7.69, 7.82, 8.32. Example 4-1 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-2-{[2-(trifluoromethoxy)phenyl]amino}-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate The same procedure as in Example 4 was carried out using 2-(trifluoromethoxy)aniline instead of aniline, and the title compound having the following physical properties was obtained by purification using a reversed-phase HPLC column. LC-MS(A) retention time (min): 1.14; MS(ESI, Pos.): 880 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.07, 1.76-2.09, 2.24-2.37, 2.55, 2.80-2.96, 3.02-3.20, 3.59-4.07, 4.58-5.03, 5.24-5.64, 6.73-7.26, 7.30-7.48, 7.51-7.72, 7.90-8.07, 8.20-8.30, 8.73-8.98. Example 5 2-(Cyclopentyloxy)-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[(3R)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate The compound (18 mg) prepared in Reference Example 10 was dissolved in 1-methyl-2-pyrrolidinone (hereinafter sometimes abbreviated as NMP) (0.19 mL), and cyclopentanol (6.5 mg) and cesium carbonate (25 mg) were added, followed by stirring overnight at 110° C. The reaction solution was purified by reverse-phase HPLC column to obtain the title compound (1.3 mg) having the following physical properties: LC-MS(A) retention time (min): 1.14; MS(ESI, Pos.): 789 (M + H) + ; 1H-NMR(DMSO-d6):δ 1.00-1.11, 1.56-1.66, 1.66-1.79, 1.91-2.11, 2.81-2.90, 3.07-3.25, 3.62-3.80, 3.90-4.15, 4.79-5.06, 5.27-5.44, 5.51-5.65, 6.36-6.72, 6.88-7.17, 7.23-7.41, 7.48-7.82, 7.92-7.97, 8.19-8.33, 8.64-8.77. Example 6 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-2-(4-methoxyphenyl)-6-methyl-7,9-dihydro-8H-purin-8-one The compound (20 mg) prepared in Reference Example 10 was dissolved in NMP (0.4 mL), and (4-methoxyphenyl)boronic acid (16 mg), an aqueous solution of tripotassium phosphate (0.054 mL, 2 mol / L), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (8.8 mg) were added thereto, followed by stirring at 100°C for 4 hours. The reaction solution was cooled to room temperature, and water was added thereto, followed by extraction with ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, and then The residue obtained by concentration under reduced pressure was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate=7:3→0:1) to obtain the title compound (4.4 mg) having the following physical properties: LC-MS(A) retention time (min): 1.16; MS(ESI, Pos.): 811 (M + H) + ; 1 H-NMR (CDCl3):δ 0.89, 1.76-1.85, 1.90-1.99, 2.14-2.24, 2.36-2.46, 2.50-2.61, 2.83-2.98, 3.28, 3.74-4.13, 3.89, 4.67-4.95, 5.28-5.59, 6.68-6.79, 6.80-6.96, 6.97-7.03, 7.07-7.13, 7.44-7.70, 7.78-7.85, 8.28-8.41. Reference example 11 2-chloro-N-(2,4-dimethoxybenzyl)-6-methyl-5-nitro-4-pyrimidinamine 2,4-Dichloro-6-methyl-5-nitropyrimidine (1.0 g) was dissolved in THF (20 mL) and cooled to -70 °C. To this was added a THF solution (10 mL) of 1-(2,4-dimethoxyphenyl)methanamine (804 mg) and DIPEA (1.25 mL), followed by stirring at -70 °C for 2 hours. The reaction mixture was returned to room temperature, diluted with ethyl acetate, and the organic layer was washed with water and saturated brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 9:1 → 1:1) to give the title compound (1.0 g) with the following physical properties. TLC: Rf 0.27 (hexane:ethyl acetate=9:1); 1 H-NMR (CDCl3): δ 2.70., 3.81, 3.88, 4.70, 6.43-6.51, 7.23-7.28, 8.71. Reference example 12 2-chloro-N-4-(2,4-dimethoxybenzyl)-6-methyl-4,5-pyrimidinediamine Zinc (15 g) and ammonium chloride (7.5 g) were suspended in water (5 mL), and an ethyl acetate solution (20 mL) of the compound (7.9 g) produced in Reference Example 11 was added, followed by stirring at room temperature for 5 hours. The reaction mixture was filtered through Celite (trade name) to remove insoluble matter, and the filtrate was washed with saturated brine. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure to give the title compound (5.3 g) having the following physical properties: TLC: Rf 0.37 (hexane:ethyl acetate=3:7). Reference example 13 2-chloro-9-(2,4-dimethoxybenzyl)-6-methyl-7,9-dihydro-8H-purin-8-one The compound (5.3 g) prepared in Reference Example 12 was dissolved in THF (30 mL), and CDI (5.6 g) and DBU (2.6 g) were added, followed by stirring at room temperature for 16 hours. The reaction mixture was diluted with ethyl acetate and washed sequentially with 1N hydrochloric acid, saturated aqueous sodium carbonate, and saturated brine. The resulting organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was washed with MTBE and collected by filtration to give the title compound (5.8 g) having the following physical properties: TLC: Rf 0.43 (hexane:ethyl acetate=3:7); 1 H-NMR (CDCl3): δ 2.50, 3.78, 3.80, 5.07, 6.38-6.45, 7.17, 9.16-9.27. Reference example 14 Methyl 4-[2-chloro-9-(2,4-dimethoxybenzyl)-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl]benzoate The compound prepared in Reference Example 13 (1.3 g) was dissolved in acetonitrile (536 mL), and [4-(methoxycarbonyl)phenyl]boronic acid (2.2 g), N,N-diethylethanamine (hereinafter sometimes abbreviated as NEt3) (11 mL), pyridine (30 mL), and copper(II) acetate (1.5 g) were added. The atmosphere in the reaction vessel was purged with oxygen, and the mixture was stirred at room temperature for 21 hours. The reaction solution was concentrated, dissolved in ethyl acetate, and washed sequentially with aqueous ammonia, water, 1N hydrochloric acid, water, saturated sodium bicarbonate, and saturated brine. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=67:33) to give the title compound (1.5 g) having the following physical properties. TLC: Rf 0.23 (hexane:ethyl acetate=2:1); 1 H-NMR (CDCl3): δ 2.09, 3.79, 3.82, 3.96, 5.14, 6.41-6.47, 7.27-7.31, 7.43-7.48, 8.16-8.23. Reference example 15 4-[2-chloro-9-(2,4-dimethoxybenzyl)-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl]benzoic acid The compound prepared in Reference Example 14 (1.5 g) was dissolved in THF (30 mL), TMSOK (844 mg) was added, and the mixture was stirred at room temperature for 90 minutes. The reaction mixture was diluted with water and adjusted to pH 2 or less with 1N hydrochloric acid. After extraction with ethyl acetate, the resulting organic layer was washed with water and saturated brine. After drying over anhydrous sodium sulfate, the mixture was concentrated under reduced pressure to give the title compound (1.5 g) having the following physical properties: TLC: Rf 0.31 (dichloromethane:methanol=9:1); 1H-NMR (DMSO-d6): δ 1.99, 3.69-3.76, 3.79-3.87, 4.96, 6.46, 6.60, 7.03, 7.65-7.73, 8.08-8.15, 13.25. Reference example 16 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-(2,4-dimethoxybenzyl)-6-methyl-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 15 (1.6 g) and the compound prepared in Reference Example 2 (1.2 g) were dissolved in DMF (15 mL), and DIPEA (2.0 mL) and HATU (1.7 g) were added and stirred at room temperature for 15 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=33:67) to give the title compound (2.1 g) having the following physical properties: TLC: Rf 0.30 (hexane:ethyl acetate=1:2); 1 H-NMR(CDCl3):δ 2.11, 2.78-2.98, 3.79, 3.83, 4.50-4.97, 5.16, 5.24-5.60, 6.43-6.48, 6.65-7.03, 7.11, 7.28-7.35, 7.38-7.69, 7.82, 8.32. Reference example 17 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-7,9-dihydro-8H-purin-8-one sodium salt Trifluoroacetic acid (26.7 mL) and triethylsilane (2.1 mL) were added to the compound (2.1 g) produced in Reference Example 16, and the mixture was stirred at 70°C for 21 hours. The reaction mixture was cooled to room temperature and extracted with a 2N aqueous sodium hydroxide solution and water. The resulting aqueous layer was washed with MTBE, and 2N hydrochloric acid was added, and the resulting precipitate was collected by filtration. The collected material was dissolved in ethyl acetate again and extracted with a 2N aqueous sodium hydroxide solution. The resulting precipitate was collected by filtration and washed with water and ethyl acetate to give the title compound (1.5 g) having the following physical properties: TLC: Rf 0.43 (ethyl acetate); 1H-NMR (DMSO-d6): δ 1.87, 2.86, 3.61-4.08, 4.65-4.90, 5.19-5.62, 6.81-7.19, 7.19-7.81, 7.93, 8.24. Reference example 18 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-9-[3-(4-morpholinyl)propyl]-7,9-dihydro-8H-purin-8-one The compound (18 mg) prepared in Reference Example 17 was dissolved in DMF (0.3 mL), and 4-(3-chloropropyl)morpholine hydrochloride (18 mg) and cesium carbonate (59 mg) were added, followed by stirring at 80°C for 17 hours. The reaction mixture was cooled to room temperature, diluted with water, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate=33:67) to give the title compound (13 mg) having the following physical properties: LC-MS(A) retention time (min): 0.99; MS(ESI, Pos.): 713 (M + H) + ; 1 H-NMR(CDCl3):δ 2.01-2.07, 2.13, 2.43, 2.46-2.52, 2.85-2.93, 3.61-3.82, 4.13, 4.52-4.95, 5.19-5.58, 6.64-6.79, 6.85, 6.92-7.03, 7.11, 7.36-7.71, 7.82, 8.33. Example 7 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-9-[3-(4-morpholinyl)propyl]-7,9-dihydro-8H-purin-8-one The same procedure as in Example 1 was carried out using the compound (35 mg) prepared in Reference Example 18 instead of the compound prepared in Reference Example 9 to give the title compound (32 mg) having the following physical properties. LC-MS(A) retention time (min): 0.98; MS(ESI, Pos.): 770 (M + H) + ; 1H-NMR(CDCl3):δ 2.05-2.12, 2.43, 2.51, 2.88, 3.58-3.74, 3.72-4.11, 4.50-4.96, 5.22-5.62, 6.66-6.79, 6.81-6.89, 6.90-7.05, 7.11, 7.33, 7.42-7.71, 7.78-7.86, 8.32. Examples 7-1 to 7-3 The same procedures as in Reference Example 18 → Example 7 were carried out using the corresponding amine compound instead of 4-(3-chloropropyl)morpholine hydrochloride, and the title compound having the following physical properties was obtained by silica gel column purification or reverse-phase HPLC column purification. Example 7-1 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-9-(tetrahydro-3-furanyl)-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate LC-MS(A) retention time (min): 1.28; MS(ESI, Pos.): 713 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.85-2.02, 2.25-2.35, 2.55-2.61, 2.81-2.92, 3.60-3.75, 3.83-4.11, 4.13-4.24, 4.55-4.93, 5.03-5.15, 5.23-5.62, 6.84-7.20, 7.23-7.37, 7.49-7.71, 7.78, 7.91-7.98, 8.21-8.29, 9.43. Example 7-2 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-9-{2-[methyl(2,2,2-trifluoroethyl)amino]ethyl}-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate LC-MS(A) retention time (min): 1.36; MS(ESI, Pos.): 782 (M + H) + ; 1H-NMR(DMSO-d6):δ 1.86-2.03, 2.82-2.90, 3.01-3.07, 3.23-3.33, 3.43, 3.65-3.73, 3.96-4.04, 4.57-4.93, 5.24-5.61, 6.86-7.18, 7.23-7.37, 7.47-7.72, 7.80, 7.90-7.97, 8.22-8.28, 9.46. Example 7-3 3-{3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]propyl}-5,5-dimethyl-1,3-oxazolidine-2,4-dione LC-MS(A) retention time (min): 1.14; MS(ESI, Pos.): 812 (M + H) + ; 1 H-NMR (CDCl3):δ 1.55-1.59, 2.03-2.09, 2.32, 2.84-2.95, 3.63-3.73, 3.74-4.12, 4.03, 4.53-4.94, 5.19-5.60, 6.68-6.79, 6.86, 6.91-7.13, 7.35, 7.45-7.72, 7.83, 8.32. Reference example 19 2-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-isopropyl-6-methyl-7,9-dihydro-8H-purin-8-one The same procedure as in Reference Example 18 was carried out using 2-iodopropane instead of 4-(3-chloropropyl)morpholine hydrochloride used in Reference Example 18 to give the title compound having the following physical properties. TLC: Rf 0.39 (hexane:ethyl acetate=1:2); 1 H-NMR(CDCl3):δ 1.64, 2.11, 2.83-2.91, 3.64-4.18, 4.53-4.95, 5.20-5.60, 6.67-6.80, 6.80-6.91, 6.91-7.05, 7.11, 7.37-7.71, 7.82, 8.32. Example 8 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-isopropyl-2,6-dimethyl-7,9-dihydro-8H-purin-8-one The compound (39 mg) prepared in Reference Example 19 was dissolved in DME (1 mL), and trimethylboroxine (39 mg), an aqueous solution of tripotassium phosphate (0.062 mL, 2 mol / L), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (4.5 mg) were added. The mixture was stirred at 140°C for 1 hour using a microwave device. The reaction solution was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative TLC (dichloromethane:methanol = 9:1) to give the title compound (30 mg) having the following physical properties. LC-MS(A) retention time (min): 0.96; MS(ESI, Pos.): 608 (M + H) + ; 1 H-NMR((CDCl3):δ 1.64, 2.03-2.15, 2.67, 2.81-2.98, 3.70-4.17, 4.57-4.95, 5.31-5.61, 6.66-6.78, 6.81-6.91, 6.90-7.05, 7.11, 7.41-7.71, 7.82, 8.32. Example 9 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-isopropyl-6-methyl-8-oxo-8,9-dihydro-7H-purine-2-carbonitrile The compound (69 mg) prepared in Reference Example 19 was dissolved in DMSO (1 mL), and N,N,N-tributyl-1-butanaminium cyanide (88 mg) and DBU (0.036 mL) were added, followed by stirring at 100°C for 2 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=33:67) to give the title compound (64 mg) having the following physical properties. LC-MS(A) retention time (min): 1.23; MS(ESI, Pos.): 619 (M + H) + ; 1H-NMR(CDCl3):δ 1.63-1.69, 2.15, 2.84-3.03, 3.69-4.10, 4.53-5.00, 5.22-5.61, 6.69-6.78, 6.77-6.90, 6.91-7.04, 7.11, 7.39-7.73, 7.82, 8.32. Reference example 20 Methyl 4-[9-(2,4-dimethoxybenzyl)-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl]benzoate The compound (120 mg) prepared in Reference Example 14 was dissolved in THF (5 mL) and methanol (5 mL), and NEt (0.043 mL) and 5% palladium-activated carbon (50% wet, 50 mg) were added. The atmosphere in the reaction vessel was replaced with hydrogen, and the mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through Celite (trade name), and the obtained filtrate was concentrated under reduced pressure to give the title compound (120 mg) having the following physical properties. LC-MS (B) retention time (min): 0.86; MS(ESI, Pos.): 435 (M + H) + ; 1 H-NMR (CDCl3): δ 3.77-3.84, 3.96, 5.18, 6.41-6.45, 6.45, 7.23, 7.46-7.53, 8.18-8.23, 8.64. Reference example 21 4-[9-(2,4-dimethoxybenzyl)-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl]benzoic acid The compound (120 mg) prepared in Reference Example 20 was dissolved in THF (0.6 mL) and methanol (0.6 mL), and 2N aqueous sodium hydroxide solution (0.28 mL) was added and stirred at room temperature for 3 hours. 2N hydrochloric acid was added to the reaction mixture to adjust the pH to about 3, followed by extraction with ethyl acetate, and the organic layer was washed with saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure to give the title compound (106 mg) having the following physical properties: LC-MS (B) retention time (min): 0.76; MS(ESI, Pos.): 421 (M + H) + . Reference example 22 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-(2,4-dimethoxybenzyl)-6-methyl-7,9-dihydro-8H-purin-8-one The same procedure as in Reference Example 16 was carried out using the compound (106 mg) prepared in Reference Example 21 instead of the compound prepared in Reference Example 15 to give the title compound (142 mg) having the following physical properties. LC-MS (B) retention time (min): 0.96; MS(ESI, Pos.): 702 (M + H) + ; 1 H-NMR(DMSO-d6):δ 2.05, 2.87, 3.61-4.09, 3.75, 3.83, 4.64-4.92, 5.03, 5.24-5.61, 6.45, 6.61, 6.88-7.17, 7.23-7.41, 7.51-7.74, 7.94, 8.25, 8.55. Reference example 23 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-7,9-dihydro-8H-purin-8-one Trifluoroacetic acid (1.5 mL) and triethylsilane (0.16 mL) were added to the compound (142 mg) prepared in Reference Example 22, and the mixture was stirred at 80° C. for 16 hours. The reaction mixture was cooled to room temperature, and saturated aqueous sodium bicarbonate solution was added, followed by extraction with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound (89 mg) having the following physical properties: LC-MS (B) retention time (min): 0.76; MS(ESI, Pos.):552 (M + H) + . Example 10 9-benzyl-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-7,9-dihydro-8H-purin-8-one The same procedure as in Reference Example 18 was carried out using the compound prepared in Reference Example 23 instead of the compound prepared in Reference Example 17 and (bromomethyl)benzene instead of 4-(3-chloropropyl)morpholine hydrochloride to obtain the title compound having the following physical properties. LC-MS (B) retention time (min): 0.94; MS(ESI, Pos.): 642 (M + H) + ; 1H-NMR (DMSO-d6):δ 2.01-2.08, 2.84-2.90, 3.59-4.01, 4.55-4.96, 5.14, 5.21-5.64, 6.84-7.10, 7.14, 7.29-7.45, 7.53-7.77, 7.94, 8.25, 8.59. Example 11 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-9-phenyl-7,9-dihydro-8H-purin-8-one The compound (49 mg) prepared in Reference Example 23 was dissolved in DMF (0.88 mL), and phenylboronic acid (32 mg), pyridine (0.072 mL), and copper(II) acetate (18 mg) were added, followed by stirring at room temperature for 24 hours. Aqueous ammonia was added to the reaction mixture, which was then extracted with ethyl acetate and washed with water and saturated brine. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative TLC (ethyl acetate) to give the title compound (15 mg) having the following physical properties: LC-MS (B) retention time (min): 0.94; MS(ESI, Pos.): 628 (M + H) + ; 1 H-NMR(CDCl3):δ 2.20, 2.84-3.00, 3.73-4.11, 4.57-4.97, 5.32-5.62, 6.68-6.79, 6.81-6.92, 6.92-7.03, 7.11, 7.42-7.51, 7.52-7.76, 7.83, 8.32, 8.62-8.69. Reference example 24 2-Methyl-2-propanyl (3R)-3-{[2-(benzylamino)-6-methyl-5-nitro-4-pyrimidinyl]amino}-1-piperidinecarboxylate 2,4-Dichloro-6-methyl-5-nitropyrimidine (1.5 g) was dissolved in THF (30 mL) and a THF solution (10 mL) of DIPEA (1.9 mL) and 2-methyl-2-propanyl (3R)-3-amino-1-piperidinecarboxylate (1.5 g) was added at 0 °C. The mixture was stirred at 0 °C for 2 hours and then at room temperature overnight. The reaction mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 9:1 → 1:1). The resulting compound (400 mg) was dissolved in THF (10 mL), and DIPEA (0.21 mL) and 1-phenylmethanamine (0.13 mL) were added. The mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure to give a residue, which was purified by silica gel chromatography (hexane:ethyl acetate=4:1→3:2) to give the title compound (303 mg) having the following physical properties: TLC: Rf 0.45 (hexane:ethyl acetate=7:3). Reference example 25 2-Methyl-2-propanyl (3R)-3-{[5-amino-2-(benzylamino)-6-methyl-4-pyrimidinyl]amino}-1-piperidinecarboxylate The same procedure as in Reference Example 12 was carried out using the compound (300 mg) prepared in Reference Example 24 instead of the compound prepared in Reference Example 11 to give the title compound (275 mg) having the following physical properties. TLC: Rf 0.35 (Fuji Silysia NH (trade name), ethyl acetate). Reference example 26 2-Methyl-2-propanyl (3R)-3-[2-(benzylamino)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate The same procedure as in Reference Example 13 was carried out using the compound (275 mg) prepared in Reference Example 25 instead of the compound prepared in Reference Example 12 to give the title compound (199 mg) having the following physical properties. TLC: Rf 0.25 (Fuji Silysia NH (trade name), ethyl acetate); 1H-NMR(CDCl3):δ 1.40-1.48, 1.72-1.89, 2.33, 2.49-2.76, 3.43-3.62, 3.90-4.38, 4.58, 5.18-5.30, 7.27-7.38, 7.69. Example 12 2-Methyl-2-propanyl (3R)-3-[2-(benzylamino)-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate The compound prepared in Reference Example 26 was used instead of the compound prepared in Reference Example 13, and the same procedures as in Reference Example 14 → Reference Example 15 → Reference Example 16 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.20; MS(ESI, Pos.): 840 (M + H) + ; 1 H-NMR(CDCl3):δ 1.40-1.51, 1.71-1.82, 1.84-1.94, 1.97, 2.29-2.48, 2.55-2.77, 2.88, 3.60, 3.72-4.21, 4.36, 4.52-4.97, 5.21-5.62, 6.68-6.79, 6.80-7.00, 7.10, 7.22-7.26, 7.27-7.41, 7.47, 7.60, 7.82, 8.32. Reference example 27 4-Methyl 1-(2-methyl-2-propanyl) 4-(2-chloro-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl)-1,4-piperidinedicarboxylate Using 4-methyl 1-(2-methyl-2-propanyl) 4-amino-1,4-piperidinecarboxylate instead of 1-(2,4-dimethoxyphenyl)methanamine used in Reference Example 11, the same procedures as in Reference Example 11 → Reference Example 12 → Reference Example 13 were carried out to obtain the title compound having the following physical properties. TLC: Rf 0.60 (hexane:ethyl acetate=1:4); 1 H-NMR (CDCl3): δ 1.47, 2.21-2.36, 2.51, 3.07-3.23, 3.29-3.56, 3.76, 9.25-9.49. Reference example 28 4-Methyl 1-(2-methyl-2-propanyl) 4-(7-{4-[(benzyloxy)carbonyl]phenyl}-2-chloro-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl)-1,4-piperidinedicarboxylate The same procedure as in Reference Example 14 was carried out using the compound (195 mg) prepared in Reference Example 27 instead of the compound prepared in Reference Example 13 and {4-[(benzyloxy)carbonyl]phenyl}boronic acid instead of [4-(methoxycarbonyl)phenyl]boronic acid to obtain the title compound (98 mg) having the following physical properties. TLC: Rf 0.30 (Fuji Silysia NH (trade name), hexane:ethyl acetate=3:1); 1 H-NMR(CDCl3):δ 1.48, 2.07, 2.24-2.39, 3.10-3.23, 3.44-3.60, 3.64-3.75, 3.78, 5.40, 7.35-7.51, 8.21-8.27. Reference example 29 4-Methyl 1-(2-methyl-2-propanyl) 4-(2-anilino-7-{4-[(benzyloxy)carbonyl]phenyl}-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl)-1,4-piperidinedicarboxylate The same procedure as in Example 1 was carried out using the compound (30 mg) prepared in Reference Example 28 instead of the compound prepared in Reference Example 9 to give the title compound (32 mg) having the following physical properties. TLC: Rf 0.28 (Fuji Silysia NH (trade name), hexane:ethyl acetate=7:3); 1 H-NMR(CDCl3):δ 1.46, 2.01, 2.25-2.38, 3.14-3.29, 3.48-3.60, 3.65-3.77, 5.40, 6.91, 7.03, 7.28-7.54, 8.22. Example 13 4-Methyl 1-(2-methyl-2-propanyl) 4-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1,4-piperidinedicarboxylate The compound prepared in Reference Example 29 (30 mg) was dissolved in THF (1.5 mL) and methanol (1.5 mL), and 5% palladium-activated carbon (50% wet, 30 mg) was added. The atmosphere in the reaction vessel was replaced with hydrogen and stirred at room temperature for 2 hours. The reaction solution was filtered through Celite (trade name), and the resulting filtrate was concentrated under reduced pressure. This was dissolved in DMF (2 mL), and the compound prepared in Reference Example 2 (15 mg), NEt3 (0.023 mL), and HATU (24 mg) were added and stirred at room temperature for 2 hours. The reaction solution was diluted with water and extracted with ethyl acetate. The resulting organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue obtained was purified by silica gel chromatography (hexane:ethyl acetate = 2:3 → 3:7) to give the title compound (33 mg) with the following physical properties. LC-MS(A) retention time (min): 1.27; MS(ESI, Pos.): 884 (M + H) + ; 1 H-NMR(CDCl3):δ 1.42-1.54, 2.04, 2.24-2.44, 2.82-2.96, 3.16-3.32, 3.48-3.61, 3.66-4.17, 4.54-4.94, 5.26-5.56, 6.69-6.78, 6.79-6.99, 6.99-7.08, 7.11, 7.27-7.39, 7.40-7.69, 7.75-7.87, 8.27-8.35. Reference example 30 2-Methyl-2-propanyl 9-(2,4-difluorobenzyl)-5-methoxy-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate The compound (200 mg) prepared in Reference Example 1 and tetraethylammonium p-toluenesulfonate (1206 mg) were dissolved in methanol (20 mL). The reaction solution was electrified (Kikusui DC power supply: PMC350-0.2A, 12 mA, anode: carbon felt, cathode: platinum plate) and stirred for 30 minutes. Ethyl acetate was added to the reaction solution and stirred, and the precipitated crystals were filtered off. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=4:1) to give the title compound (9.8 mg) having the following physical properties. TLC: Rf 0.28 (hexane:ethyl acetate=3:1); 1 H-NMR(CDCl3):δ 1.42-1.54, 3.20-3.47, 3.53, 4.08-4.45, 4.55-4.68, 4.73-5.10, 5.37-5.54, 6.69-6.78, 6.83, 6.90-7.15, 7.94, 8.31. Reference example 31 2-Methyl-2-propanyl 9-(2,4-difluorobenzyl)-5-hydroxy-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate The compound (9.8 mg) prepared in Reference Example 30 was dissolved in 1,4-dioxane (0.16 mL), and water (0.040 mL) and 4-methylbenzenesulfonic acid hydrate (0.87 mg) were added. The mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by preparative TLC (hexane:ethyl acetate=1:1) to give the title compound (9.0 mg) having the following physical properties. TLC: Rf 0.38 (hexane:ethyl acetate=1:1); 1 H-NMR(CDCl3):δ 1.49, 3.47, 4.11-4.31, 4.76-5.09, 5.36-5.55, 6.71-6.87, 6.95-7.13, 7.13, 8.01, 8.32. Reference example 32 9-(2,4-Difluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-5-ol The compound (9.0 mg) prepared in Reference Example 31 was dissolved in dichloromethane (0.4 mL), trifluoroacetic acid (0.2 mL) was added, and the mixture was stirred at 0°C for 90 minutes. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to give the title compound (5.1 mg) having the following physical properties: TLC: Rf 0.22 (dichloromethane:methanol=9:1); 1 H-NMR (CDCl3): δ 3.04, 3.28, 3.75-4.01, 4.91, 5.19-5.52, 6.68-6.87, 6.97, 7.12, 7.99, 8.31. Reference example 33 2-Methyl-2-propanyl (3S)-3-{2-chloro-7-[4-(methoxycarbonyl)phenyl]-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl}-1-piperidinecarboxylate Using 2-methyl-2-propanyl (3S)-3-amino-1-piperidinecarboxylate instead of 2-methyl-2-propanyl 4-amino-1-piperidinecarboxylate used in Reference Example 3, the same procedures as in Reference Example 3 → Reference Example 4 → Reference Example 5 were carried out to obtain the title compound having the following physical properties. TLC: Rf 0.35 (hexane:ethyl acetate=2:1); 1 H-NMR(CDCl3):δ 1.47, 1.61-1.81, 1.82-1.90, 1.95-2.03, 2.09, 2.43-2.61, 2.68-2.86, 3.59-3.75, 3.93-4.00, 4.07-4.29, 4.43-4.54, 7.49, 8.23. Reference example 34 Methyl 4-{2-chloro-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl}benzoate The same procedures as in Reference Example 8→Reference Example 9 were carried out using the compound prepared in Reference Example 33 instead of the compound prepared in Reference Example 7 to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 0.96; MS(ESI, Pos.): 472 (M + H) + . Reference example 35 Methyl 4-{2-anilino-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl}benzoate The same procedure as in Example 1 was carried out using the compound (1.4 g) prepared in Reference Example 34 instead of the compound prepared in Reference Example 9 to give the title compound (1.1 g) having the following physical properties. LC-MS(A) retention time (min): 1.01; MS(ESI, Pos.):529 (M + H) + . Reference example 36 4-{2-Anilino-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl}benzoic acid monohydrochloride The compound (106 mg) prepared in Reference Example 35 was dissolved in THF (2 mL), and TMSOK (57 mg) was added and stirred at room temperature for 90 minutes. A 4N solution of hydrogen chloride in 1,4-dioxane was added to the reaction mixture, which was then concentrated to give the title compound (110 mg) having the following physical properties: TLC: Rf 0.35 (dichloromethane:methanol=9:1). Example 14 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5-hydroxy-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[(3S)-1-(2,2-dimethylpropyl)-3-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one The same procedure as in Reference Example 7 was carried out using the compound (5.1 mg) prepared in Reference Example 32 instead of the compound prepared in Reference Example 2, and the compound prepared in Reference Example 36 instead of the compound prepared in Reference Example 6, to obtain the title compound (6.8 mg) having the following physical properties. LC-MS(A) retention time (min): 1.06; MS(ESI, Pos.): 812 (M + H) + ; 1 H-NMR (CDCl3):δ 0.86-0.90, 1.73-1.81, 1.85-1.93, 2.01-2.06, 2.08-2.21, 2.29-2.53, 2.75-2.94, 3.23, 3.46-3.72, 4.11-4.21, 4.25-4.45, 4.63, 5.07, 5.28-5.67, 6.68-6.78, 6.86, 6.98-7.12, 7.16, 7.34, 7.48, 7.63-7.88, 8.00, 8.34. Reference example 37 2-Methyl-2-propanyl 3-[(2-anilino-5-nitro-4-pyrimidinyl)amino]-1-piperidinecarboxylate 2,4-Dichloro-5-nitropyrimidine (4.8 g) was dissolved in THF (40 mL), and a THF solution (10 mL) of 2-methyl-2-propanyl 3-amino-1-piperidinecarboxylate (5.0 g) and DIPEA (8.5 mL) was added at 0°C. After stirring at 0°C for 1 hour, a mixture of aniline (2.3 g) and DIPEA (8.5 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with a mixture of ethyl acetate and methanol (1:1), and the resulting precipitate was collected by filtration to give the title compound (5.9 g) with the following physical properties. LC-MS(A) retention time (min): 1.27; MS(ESI, Pos.): 415 (M + H) + . Reference example 38 2-Methyl-2-propanyl 3-[(5-amino-2-anilino-4-pyrimidinyl)amino]-1-piperidinecarboxylate The compound prepared in Reference Example 37 (1.0 mg) was dissolved in DMF (100 mL), 5% palladium-activated carbon (50% wet, 280 mg) was added, the atmosphere in the reaction vessel was replaced with hydrogen, and the mixture was stirred at room temperature for 5 hours. The reaction solution was filtered through Celite (trade name), and the filtrate was diluted with a mixture of ethyl acetate and hexane (3:7) and washed with water and saturated brine. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound (680 mg) having the following physical properties: LC-MS(A) retention time (min): 1.00; MS(ESI, Pos.): 385 (M + H) + . Reference example 39 2-Methyl-2-propanyl 3-(2-anilino-8-oxo-7,8-dihydro-9H-purin-9-yl)-1-piperidinecarboxylate The same procedure as in Reference Example 13 was carried out using the compound (3.7 g) prepared in Reference Example 38 instead of the compound prepared in Reference Example 12 to give the title compound (1.7 g) having the following physical properties. LC-MS(A) retention time (min): 1.00; MS(ESI, Pos.): 411 (M + H) + . Reference example 40 2-Methyl-2-propanyl 3-{2-anilino-7-[4-(methoxycarbonyl)phenyl]-8-oxo-7,8-dihydro-9H-purin-9-yl}-1-piperidinecarboxylate The same procedure as in Reference Example 14 was carried out using the compound (1.6 g) prepared in Reference Example 39 instead of the compound prepared in Reference Example 13 to give the title compound (690 mg) having the following physical properties. LC-MS(A) retention time (min): 1.20; MS(ESI, Pos.):545 (M + H) + ; 1H-NMR(DMSO-d6):δ 1.42, 1.46-1.59, 1.80-1.89, 1.94-2.03, 2.68-2.83, 3.46-3.69, 3.90, 4.01-4.19, 4.27, 6.93, 7.28, 7.76, 7.81-7.86, 8.11-8.15, 8.31, 9.55. Reference example 41 4-[2-anilino-9-(1-{[(2-methyl-2-propanyl)oxy]carbonyl}-3-piperidinyl)-8-oxo-8,9-dihydro-7H-purin-7-yl]benzoic acid The same procedure as in Reference Example 6 was carried out using the compound (686 mg) prepared in Reference Example 40 instead of the compound prepared in Reference Example 5 to give the title compound (356 mg) having the following physical properties. LC-MS(A) retention time (min): 1.16; MS(ESI, Pos.):531 (M + H) + . Reference example 42 2-Methyl-2-propanyl 3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate The same procedure as in Reference Example 7 was carried out using the compound (207 mg) prepared in Reference Example 41 instead of the compound prepared in Reference Example 6 to give the title compound (287 mg) having the following physical properties. LC-MS(A) retention time (min): 1.28; MS(ESI, Pos.): 812 (M + H) + ; 1 H-NMR (CDCl3):δ 1.43-1.53, 1.64-1.77, 1.83-1.95, 1.99-2.04, 2.55-2.69, 2.72-2.96, 3.69-3.86, 4.09-4.37, 4.49, 4.55-4.93, 5.25-5.59, 6.68-6.79, 6.81-6.89, 6.90-7.00, 7.02-7.13, 7.35, 7.51-7.70, 7.83, 8.11, 8.32. Reference example 43 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-(3-piperidinyl)-7,9-dihydro-8H-purin-8-one dihydrochloride The compound (170 mg) prepared in Reference Example 42 was suspended in methanol (3 mL), and a 4N hydrogen chloride / 1,4-dioxane solution (1.0 mL) was added and stirred at room temperature for 2 hours. The reaction mixture was concentrated to give the title compound (167 mg) having the following physical properties: LC-MS(A) retention time (min): 1.02; MS(ESI, Pos.): 712 (M + H) + . Example 15 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(3,3-dimethylbutyl)-3-piperidinyl]-7,9-dihydro-8H-purin-8-one The compound (14 mg) prepared in Reference Example 43 was dissolved in dichloromethane (1.0 mL), and 3,3-dimethylbutanal (18 mg) and sodium triacetoxyborohydride (38 mg) were added. The mixture was stirred at room temperature for 4 hours. The reaction mixture was ice-cooled, and saturated aqueous sodium bicarbonate solution was added. After extraction with ethyl acetate, the organic layer was washed with water and saturated brine. The residue obtained after drying over anhydrous sodium sulfate and concentration under reduced pressure was purified by silica gel chromatography (hexane:ethyl acetate = 1:1 → 0:1) to give the title compound (4.9 mg) having the following physical properties. LC-MS(A) retention time (min): 1.15; MS(ESI, Pos.): 796 (M + H) + ; 1 H-NMR(DMSO-d6):δ 0.91, 1.50-1.67, 1.80-1.93, 2.05-2.19, 2.82-2.99, 3.14-3.32, 3.63-3.75, 3.79-3.89, 3.95-4.07, 4.58-4.93, 5.26-5.67, 6.93-7.10, 7.11-7.18, 7.28-7.37, 7.51-7.81, 7.94, 8.20-8.39, 9.54, 9.60-9.75. Example 15-1 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-3-piperidinyl]-2-(2-pyridinylamino)-7,9-dihydro-8H-purin-8-one Using 2-aminopyridine instead of aniline used in Reference Example 37 and pivalaldehyde instead of 3,3-dimethylbutanal used in Example 15, the same operations as in Reference Example 37 → Reference Example 38 → Reference Example 39 → Reference Example 40 → Reference Example 41 → Reference Example 42 → Reference Example 43 → Example 15 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 0.96; MS(ESI, Pos.): 783 (M + H) + ; 1 H-NMR(CDCl3):δ 0.84-0.91, 1.75-1.85, 1.93, 2.08-2.24, 2.32-2.52, 2.82-2.98, 3.15-3.25, 3.70-4.16, 4.41, 4.54-4.94, 5.24-5.60, 6.50, 6.64, 6.68-6.79, 6.85, 6.89-7.00, 7.11, 7.42, 7.51-7.73, 7.83, 8.07, 8.17, 8.29-8.34, 8.41. Example 16 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(3,3-dimethylbutanoyl)-3-piperidinyl]-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 43 (10 mg) and 3,3-dimethylbutanoic acid (4.4 mg) were dissolved in DMF (0.5 mL), DIPEA (0.021 mL) and HATU (9.7 mg) were added, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate and washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1 → 0:1) to give the title compound (7.6 mg) with the following physical properties. LC-MS(A) retention time (min): 1.23; MS(ESI, Pos.): 810 (M + H) + ; 1H-NMR(CDCl3):δ 1.08, 1.91-2.02, 2.05-2.12, 2.28-2.38, 2.56-2.77, 2.80, 2.86-2.96, 3.04-3.65, 3.71-3.88, 3.69-4.09, 4.40-4.55, 4.56-4.97, 5.23-5.62, 6.68-6.79, 6.79-6.99, 7.00-7.14, 7.35, 7.50-7.72, 7.83, 8.12, 8.32. Example 17 2-Methyl-2-propanyl (3S)-3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-pyrrolidinecarboxylate

[0469] [ka]

[0470] Using 2-methyl-2-propanyl (3S)-3-amino-1-pyrrolidinecarboxylate instead of 2-methyl-2-propanyl 3-amino-1-piperidinecarboxylate used in Reference Example 37, the same procedures as in Reference Example 37 → Reference Example 38 → Reference Example 39 → Reference Example 40 → Reference Example 41 → Reference Example 42 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.21; MS(ESI, Pos.): 798 (M + H) + ; 1 H-NMR (CDCl3):δ 1.43-1.54, 2.05, 2.23-2.36, 2.82-3.01, 3.43-3.59, 3.69-4.15, 4.56-4.93, 5.07-5.22, 5.23-5.60, 6.67-7.00, 7.02-7.15, 7.35, 7.56-7.69, 7.82, 8.12, 8.32. Example 18 2-Methyl-2-propanyl (3S)-3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-fluorophenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-pyrrolidinecarboxylate Using 2-methyl-2-propanyl (3S)-3-amino-1-pyrrolidinecarboxylate instead of 2-methyl-2-propanyl 3-amino-1-piperidinecarboxylate used in Reference Example 37, and using [3-fluoro-4-(methoxycarbonyl)phenyl]boronic acid instead of [4-(methoxycarbonyl)phenyl]boronic acid used in Reference Example 40, the same procedures as in Reference Example 37 → Reference Example 38 → Reference Example 39 → Reference Example 40 → Reference Example 41 → Reference Example 42 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.24; MS(ESI, Pos.): 816 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.36-1.50, 2.19-2.35, 2.70-2.93, 3.61-3.77, 3.83-3.93, 3.94-4.12, 4.66, 4.91, 5.01-5.19, 5.30-5.39, 5.44-5.59, 6.89-7.00, 7.01-7.16, 7.23-7.36, 7.47-7.57, 7.59-7.72, 7.73-7.79, 7.97, 8.19-8.27, 8.28-8.38, 9.54-9.63. Example 19 2-Methyl-2-propanyl {3-[2-anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]propyl}carbamate Using 2-methyl-2-propanyl (3-aminopropyl)carbamate instead of 2-methyl-2-propanyl 3-amino-1-piperidinecarboxylate used in Reference Example 37, the same procedures as in Reference Example 37 → Reference Example 38 → Reference Example 39 → Reference Example 40 → Reference Example 41 → Reference Example 42 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.27; MS(ESI, Pos.): 786 (M + H) + ; 1H-NMR(DMSO-d6):δ 1.36, 1.89-2.01, 2.80-2.88, 3.02-3.09, 3.64-4.07, 4.56-4.92, 5.28-5.65, 6.84-6.95, 6.98-7.18, 7.25-7.37, 7.48-7.84, 7.94, 8.20-8.29, 9.57. Reference example 44 2-Methyl-2-propanyl 4-(2-anilino-8-oxo-7,8-dihydro-9H-purin-9-yl)-1-piperidinecarboxylate Using 2-methyl-2-propanyl 4-amino-1-piperidinecarboxylate instead of 2-methyl-2-propanyl 3-amino-1-piperidinecarboxylate used in Reference Example 37, the same procedures as in Reference Example 37 → Reference Example 38 → Reference Example 39 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 0.94; MS(ESI, Pos.): 411 (M + H) + . Reference example 45 2-Anilino-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7,9-dihydro-8H-purin-8-one The same procedures as in Reference Example 8→Reference Example 9 were carried out using the compound prepared in Reference Example 44 instead of the compound prepared in Reference Example 7 to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 0.77; MS(ESI, Pos.): 381 (M + H) + . Example 20 2-Anilino-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-2-methylphenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate The compound prepared in Reference Example 45 was used instead of the compound prepared in Reference Example 39, and [4-(methoxycarbonyl)-2-methylphenyl]boronic acid was used instead of [4-(methoxycarbonyl)phenyl]boronic acid used in Reference Example 40, and the same procedures as in Reference Example 40 → Reference Example 41 → Reference Example 42 were carried out, followed by reverse-phase HPLC column purification to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.13; MS(ESI, Pos.): 796 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.01-1.14, 2.03-2.28, 2.82-2.91, 3.04-3.10, 3.14-3.22, 3.29-3.35, 3.66-3.74, 3.90-4.09, 4.53-4.92, 5.28-5.63, 6.89-6.97, 7.00-7.16, 7.25-7.39, 7.42-7.60, 7.63-7.70, 7.71-7.79, 7.97, 8.18-8.29, 8.66-8.91, 9.38-9.52. Reference example 46 2-Methyl-2-propanyl 4-[(5-amino-6-chloro-4-pyrimidinyl)amino]-1-piperidinecarboxylate 4,6-Dichloro-5-pyrimidinamine (3.5 g) and 2-methyl-2-propanyl 4-amino-1-piperidinecarboxylate (6.4 g) were dissolved in N,N-dimethylacetamide (DMA) (18 mL), DIPEA (7.4 mL) was added, and the mixture was stirred for 17 hours at 120° C. The reaction mixture was cooled to room temperature, and water was added. The resulting precipitate was washed with a 1:1 mixture of hexane and ethyl acetate and collected by filtration to give the title compound (4.4 g) having the following physical properties: LC-MS(A) retention time (min): 0.91; MS(ESI, Pos.): 328 (M + H) + . Reference example 47 2-Methyl-2-propanyl 4-(6-chloro-8-oxo-7,8-dihydro-9H-purin-9-yl)-1-piperidinecarboxylate The same procedure as in Reference Example 13 was carried out using the compound (4.4 g) prepared in Reference Example 46 instead of the compound prepared in Reference Example 12 to give the title compound (4.4 g) having the following physical properties. LC-MS(A) retention time (min): 1.00; MS(ESI, Pos.): 354 (M + H) + . Reference example 48 6-chloro-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7,9-dihydro-8H-purin-8-one The same procedures as in Reference Example 8→Reference Example 9 were carried out using the compound prepared in Reference Example 47 instead of the compound prepared in Reference Example 7 to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 0.73; MS(ESI, Pos.): 324 (M + H) + . Reference example 49 6-chloro-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7,9-dihydro-8H-purin-8-one Using the compound prepared in Reference Example 48 instead of the compound prepared in Reference Example 39, the same procedures as in Reference Example 40 → Reference Example 41 → Reference Example 42 were carried out to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.01; MS(ESI, Pos.): 725 (M + H) + . Example 21 7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-8-oxo-8,9-dihydro-7H-purine-6-carbonitrile 2-trifluoroacetate The compound (20 mg) prepared in Reference Example 49 was dissolved in DMSO (0.4 mL), and N,N,N-tributyl-1-butanaminium cyanide (11 mg) and DBU (9.3 mg) were added, followed by stirring at 100°C for 5 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified using a reverse-phase HPLC column to give the title compound (7.6 mg) having the following physical properties: LC-MS(A) retention time (min): 1.00; MS(ESI, Pos.): 716 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.06-1.11, 2.05, 2.77-2.91, 2.91-3.05, 3.29-3.34, 3.57-3.74, 4.00-4.07, 4.53-4.93, 5.13-5.65, 6.94-7.22, 7.26-7.43, 7.56-7.79, 7.89-8.06, 8.33, 8.70-8.97. Reference example 50 9-benzyl-6-chloro-7,9-dihydro-8H-purin-8-one To a solution (10 mL) of 4,6-dichloro-5-pyrimidinamine (1.0 g) and (isocyanatomethyl)benzene (811 mg) in THF, potassium 2-methyl-2-butanolate (1.6 g) was added and stirred at room temperature for 4 hours. The reaction mixture was cooled to 0°C, and 1N hydrochloric acid (54 mL) was added and stirred at room temperature for 10 minutes. The resulting precipitate was washed with water and a mixture of hexane and ethyl acetate (1:1) to give the title compound (966 mg) with the following physical properties: TLC: Rf 0.45 (hexane:ethyl acetate=1:1); 1 H-NMR (CDCl3): δ 5.11, 7.29-7.36, 7.45-7.54, 8.30-8.45, 8.51. Reference example 51 6-Amino-9-benzyl-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 50 (3.9 g) was dissolved in DMF (30 mL), sodium azide (1.9 g) was added, and the mixture was stirred at 70°C for 16 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with dichloromethane. The resulting organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure, and the resulting residue was washed with a mixture of MTBE and hexane (1:4) and filtered. The resulting compound (3.5 g) was dissolved in THF (20 mL), trimethylphosphine (13 mL, 1.0 mol / L, THF solution) was added, and the mixture was stirred at 70°C for 16 hours. Water (3 mL) was then added to the reaction mixture, and the mixture was stirred at 70°C for 2 hours. The reaction mixture was concentrated, and the resulting residue was purified by reverse-phase silica gel column chromatography (water:acetonitrile = 9:1 → 1:9) to give the title compound (1.0 g) with the following physical properties. LC-MS (B) retention time (min): 0.53; MS(ESI, Pos.): 242 (M + H) + . Example 22 6-Amino-9-benzyl-7-(4-{[9-(2,4-difluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-7,9-dihydro-8H-purin-8-one The compound prepared in Reference Example 51 was used instead of the compound prepared in Reference Example 39, and the same procedures as in Reference Example 40 → Reference Example 41 → Reference Example 42 were carried out to obtain the title compound having the following physical properties. LC-MS (B) retention time (min): 0.90; MS(ESI, Pos.): 643 (M + H) + ; 1 H-NMR(DMSO-d6):δ 2.77-2.88, 3.65-4.04, 4.63-4.90, 5.00-5.09, 5.27-5.61, 5.93-6.11, 6.90-7.18, 7.23-7.42, 7.44-7.68, 7.92, 8.14-8.18, 8.19-8.26. Reference example 52 2-Methyl-2-propanyl 9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate 2-Methyl-2-propanyl 5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate (CAS: 1354801-07-2, 820 mg) and 4-(chloromethyl)-3-fluorobenzonitrile (560 mg) were dissolved in DMF (8.2 mL). The reaction mixture was ice-cooled, and sodium hydride (60% paraffin oil suspension, 144 mg) was added and stirred for 30 minutes. Saturated aqueous ammonium chloride was added to the reaction mixture, followed by stirring and extraction with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 67:33) to give the title compound (1.3 g) with the following physical properties. TLC: Rf 0.40 (hexane:ethyl acetate=2:1); 1 H-NMR (CDCl3): δ 1.47, 2.81, 3.75, 4.51, 5.52, 6.83-7.06, 7.10, 7.39, 7.82, 8.27. Reference example 53 3-Fluoro-4-(5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-ylmethyl)benzonitrile dihydrochloride The compound (1.3 g) prepared in Reference Example 52 was dissolved in methanol (2 mL), and 4N hydrogen chloride / 1,4-dioxane solution (7.8 mL) was added and stirred at room temperature for 40 minutes. The reaction solution was concentrated, washed with MTBE, and filtered to give the title compound (1.1 g) having the following physical properties: TLC: Rf 0.39 (dichloromethane:methanol=9:1); 1 H-NMR (DMSO-d6): δ 2.99, 3.40-3.56, 4.37, 5.61, 6.99, 7.18, 7.59, 7.93, 8.02, 8.26, 9.76. Reference example 54 2-Methyl-2-propanyl 4-[2-chloro-7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate The compound prepared in Reference Example 53 (872 mg) and the compound prepared in Reference Example 6 (976 mg) were dissolved in DMF (10 mL), DIPEA (1.4 mL) and HATU (1.1 g) were added, and the mixture was stirred at room temperature for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate=1:3) to give the title compound (1.0 g) having the following physical properties: LC-MS(A) retention time (min): 1.26; MS(ESI, Pos.): 776 (M + H) + ; 1 H-NMR(CDCl3):δ 1.45-1.55, 1.76-1.92, 2.11, 2.53-2.69, 2.78-3.00, 3.69-4.11, 4.24-4.42, 4.47-4.94, 5.31-5.67, 6.89-7.00, 7.14, 7.28-7.36, 7.37-7.73, 7.85, 8.31. Reference example 55 4-[(7-{4-[2-chloro-6-methyl-8-oxo-9-(4-piperidinyl)-8,9-dihydro-7H-purin-7-yl]benzoyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile dihydrochloride The compound (324 mg) prepared in Reference Example 54 was dissolved in 1,4-dioxane (0.32 mL) and 2-propanol (0.97 mL), and then 4N hydrogen chloride / 1,4-dioxane solution (1.6 mL) was added and stirred at room temperature for 1 hour. The reaction mixture was diluted with MTBE, and the precipitate was collected by filtration to give the title compound (280 mg) having the following physical properties: LC-MS(A) retention time (min): 0.94; MS(ESI, Pos.): 676 (M + H) + . Reference example 56 4-{[7-(4-{2-chloro-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl}benzoyl)-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl]methyl}-3-fluorobenzonitrile The compound prepared in Reference Example 55 (280 mg) was dissolved in DMF (2.8 mL) and NEt (0.16 mL) was added. To the resulting mixture, pivalaldehyde (169 mg), acetic acid (0.23 mL), and sodium triacetoxyborohydride (250 mg) were added and stirred at room temperature for 3 hours. The reaction mixture was ice-cooled, and saturated aqueous sodium bicarbonate solution was added. After extraction with a mixture of hexane and ethyl acetate (3:7), the organic layer was washed with saturated aqueous sodium bicarbonate and water and dried over anhydrous sodium sulfate. The residue obtained after concentration under reduced pressure was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate = 3:1 → 0:1) to give the title compound (230 mg) with the following physical properties. LC-MS(A) retention time (min): 1.02; MS(ESI, Pos.): 746 (M + H) + ; 1 H-NMR(CDCl3):δ 0.90, 1.62-1.80, 2.13, 2.41-2.50, 2.65-2.80, 2.85-3.01, 3.70-4.12, 4.43, 4.50-4.92, 5.34-5.66, 6.94, 7.14, 7.27-7.36, 7.39-7.72, 7.85, 8.31. Example 23 1-(3-{7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)cyclopropanecarboxylic acid

[0471] [ka]

[0472] The compound prepared in Reference Example 56 (550 mg) was dissolved in NMP (7.7 mL), 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarboxylic acid (637 mg), a tripotassium phosphate aqueous solution (1.1 mL, 2 mol / L), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (120 mg) were added, and the mixture was stirred at 140 °C for 1 hour using a microwave oven. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and water was added. The resulting organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The residue obtained after concentration under reduced pressure was purified by silica gel chromatography (ethyl acetate:methanol = 1:0 → 4:1) to give the title compound (275 mg) with the following physical properties. LC-MS(A) retention time (min): 1.07; MS(ESI, Pos.): 872 (M + H) + ; 1 H-NMR(CDCl3):δ 0.94, 1.34-1.42, 1.68-1.82, 2.11-2.26, 2.51, 2.88-3.03, 3.75-4.11, 4.48, 4.54-4.91, 5.33-5.65, 6.93, 7.14, 7.27-7.33, 7.40-7.70, 7.85, 8.31, 8.39, 8.45. Example 23-1 1-(3-{7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)cyclobutanecarboxylic acid The same procedure as in Example 23 was carried out using 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclobutanecarboxylic acid instead of 1-[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropanecarboxylic acid to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.10; MS(ESI, Pos.): 886 (M + H) + ; 1H-NMR(CDCl3):δ 0.94, 1.73-1.84, 1.90-2.01, 2.08-2.23, 2.45-2.55, 2.61-2.70, 2.87-2.99, 3.00-3.08, 3.74-4.15, 4.40-4.52, 4.54-4.93, 5.32-5.69, 6.89-7.02, 7.14, 7.27-7.33, 7.39-7.56, 7.65, 7.86, 8.30-8.34, 8.47. Reference example 57 3-Fluoro-4-{[7-(4-iodobenzoyl)-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl]methyl}benzonitrile The compound prepared in Reference Example 53 (1.2 g) and 4-iodobenzoic acid (960 mg) were dissolved in DMF (24 mL), DIPEA (3.0 mL) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium chloride (hereinafter sometimes abbreviated as DMTMM) (2.1 g) were added, and the mixture was stirred at room temperature for 40 minutes. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and then passed through an inject column (Amino (trade name)), and the obtained filtrate was concentrated. The residue was washed with a mixture of hexane and ethyl acetate (2:1) to obtain the title compound (1.6 g) having the following physical properties. LC-MS(A) retention time (min): 1.20; MS(ESI, Pos.): 537 (M + H) + ; 1 H-NMR(CDCl3):δ 2.87, 3.64-4.06, 4.40-4.88, 5.28-5.66, 6.92, 7.09-7.25, 7.27-7.34, 7.40, 7.72-7.88, 8.30. Reference example 58 Ethyl 5-amino-2-chloro-6-[(1-{[(2-methyl-2-propanyl)oxy]carbonyl}-4-piperidinyl)amino]-4-pyrimidinecarboxylate 2-Methyl-2-propanyl 4-amino-1-piperidinecarboxylate (1.0 g) and ethyl 5-amino-2,6-dichloro-4-pyrimidinecarboxylate (2.2 g) were dissolved in DMA (5 mL), DIPEA (1.1 mL) was added, and the mixture was stirred at 100 °C overnight. After cooling to room temperature, water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1 → 0:1) to give the title compound (1.6 g) with the following physical properties. LC-MS(A) retention time (min): 1.10; MS(ESI, Pos.): 400 (M + H) + ; 1 H-NMR (CDCl3): δ 1.34-1.44, 1.46, 2.03-2.15, 2.93, 4.04-4.29, 4.43, 5.30, 5.52. Reference example 59 Ethyl 2-chloro-5-[(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)amino]-6-[(1-{[(2-methyl-2-propanyl)oxy]carbonyl}-4-piperidinyl)amino]-4-pyrimidinecarboxylate The compound prepared in Reference Example 57 (590 mg) and the compound prepared in Reference Example 58 (400 mg) were dissolved in 1,4-dioxane (8 mL). Cesium carbonate (489 mg), Xantphos (116 mg), and Pd2(dba)3 (92 mg) were added to the solution. The atmosphere in the reaction vessel was replaced with nitrogen, and the mixture was stirred at 100°C for 4 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 7:3 → 0:1) to give the title compound (110 mg) having the following physical properties. LC-MS(A) retention time (min): 1.26; MS(ESI, Pos.): 808 (M + H) + . Reference example 60 Ethyl 2-chloro-7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-(1-{[(2-methyl-2-propanyl)oxy]carbonyl}-4-piperidinyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxylate The compound (110 mg) prepared in Reference Example 59 was dissolved in THF (1.1 mL), CDI (44 mg) and DBU (31 mg) were added, and the mixture was stirred at room temperature for 20 minutes. Saturated aqueous ammonium chloride was added to the reaction mixture, which was then diluted with ethyl acetate. The resulting organic layer was washed with saturated aqueous ammonium chloride and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 1:1 → 0:1) to give the title compound (40 mg) having the following physical properties. LC-MS(A) retention time (min): 1.28; MS(ESI, Pos.): 834 (M + H) + ; 1 H-NMR(CDCl3):δ 1.26, 1.47-1.55, 1.80-1.94, 2.54-2.72, 2.78-3.01, 3.73-4.08, 4.09-4.16, 4.24-4.92, 5.37-5.68, 6.89-7.00, 7.10-7.17, 7.29-7.70, 7.84, 8.31. Reference example 61 Ethyl 2-chloro-7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-8-oxo-8,9-dihydro-7H-purine-6-carboxylate The same procedures as in Reference Example 55→Reference Example 56 were carried out using the compound prepared in Reference Example 60 instead of the compound prepared in Reference Example 54 to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.08; MS(ESI, Pos.): 804 (M + H) + ; 1 H-NMR(CDCl3):δ 0.86-0.96, 1.22-1.29, 1.69-1.83, 2.14, 2.41-2.51, 2.65-2.81, 2.84-3.02, 3.73-4.08, 4.38-4.92, 5.31-5.65, 6.89-7.00, 7.13, 7.27-7.37, 7.37-7.68, 7.85, 8.30. Reference example 62 Ethyl 7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purine-6-carboxylate The compound prepared in Reference Example 61 (150 mg) was dissolved in DMF (1.5 mL) and toluene (1.5 mL). 4-(trifluoromethoxy)aniline (50 mg), cesium carbonate (182 mg), Xantphos (22 mg), and palladium acetate (4.2 mg) were added and the mixture was stirred at 100°C for 1 hour under a nitrogen atmosphere. After cooling the reaction mixture to room temperature, water was added and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and the resulting residue was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate = 1:1 → 0:1) to give the title compound (160 mg) having the following physical properties. LC-MS(A) retention time (min): 1.20; MS(ESI, Pos.): 945 (M + H) + . Reference example 63 7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purine-6-carboxylic acid The compound (150 mg) prepared in Reference Example 62 was dissolved in THF (3 mL) and cooled to 0° C. To this was added TMSOK (34 mg), and the mixture was stirred at 0° C. for 2 hours. The reaction mixture was neutralized with a 4N hydrogen chloride / 1,4-dioxane solution and concentrated under reduced pressure to give the title compound (120 mg) having the following physical properties: LC-MS(A) retention time (min): 1.02; MS(ESI, Pos.): 917 (M + H) + . Example 24 7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-N-hydroxy-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purine-6-carboxamide 2-trifluoroacetate The compound prepared in Reference Example 63 (25 mg) was dissolved in DMF (0.5 mL), DIPEA (0.023 mL) and ethyl carbonochloridate (8.9 mg) were added, and the mixture was stirred at room temperature for 10 minutes. 2-(aminooxy)tetrahydro-2H-pyran (16 mg) was then added and the mixture was stirred for 10 minutes. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The resulting residue was dissolved in methanol (0.25 mL), and a 4N solution of hydrogen chloride in 1,4-dioxane (0.12 mL) was added, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified using a reverse-phase HPLC column to give the title compound (11 mg) with the following physical properties. LC-MS(A) retention time (min): 1.02; MS(ESI, Pos.): 932 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.00-1.13, 1.99-2.22, 2.79-3.02, 3.02-3.24, 3.54-4.07, 4.46-4.91, 5.36-5.77, 6.90-7.23, 7.23-7.71, 7.71-8.02, 8.15-8.31, 8.62-8.99, 8.99-9.25, 9.68-9.86, 10.94-11.11. Reference example 64 2-Methyl-2-propanyl (3S)-3-[(5-amino-2-chloro-4-pyrimidinyl)amino]-1-pyrrolidinecarboxylate 2-Methyl-2-propanyl (3S)-3-amino-1-pyrrolidinecarboxylate (7.0 g) and 2,4-dichloro-5-pyrimidinamine (5.0 g) were dissolved in DMA (35 mL), DIPEA (11.6 mL) was added, and the mixture was stirred overnight at 100 °C. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, and the organic layer was washed sequentially with 1N hydrochloric acid, water, and saturated brine. The residue obtained after drying over anhydrous sodium sulfate and concentration under reduced pressure was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate = 3:7 → 0:1) to give the title compound (5.4 g) with the following physical properties. LC-MS(A) retention time (min): 0.88; MS(ESI, Pos.): 314 (M + H) + . Reference example 65 2-Methyl-2-propanyl (3S)-3-[(2-chloro-5-{[4-(methoxycarbonyl)phenyl]amino}-4-pyrimidinyl)amino]-1-pyrrolidinecarboxylate The compound prepared in Reference Example 64 (5.4 g) and methyl 4-iodobenzoate (5.4 g) were dissolved in dehydrated DME (50 mL). Cesium carbonate (11.1 g), Xantphos (1.2 g), and Pd(dba) (937 mg) were added to the solution. The atmosphere in the reaction vessel was replaced with nitrogen, and the mixture was stirred overnight at 80°C. The reaction mixture was cooled to room temperature and passed through an inject column (Amino (trade name)) to remove insoluble matter. The filtrate was concentrated, and the resulting residue was purified by silica gel chromatography (Fuji Silysia NH (trade name), hexane:ethyl acetate = 3:7 → 1:1) to give the title compound (5.2 g) with the following physical properties. LC-MS(A) retention time (min): 1.13; MS(ESI, Pos.): 448 (M + H) + . Reference example 66 2-Methyl-2-propanyl (3S)-3-{2-chloro-7-[4-(methoxycarbonyl)phenyl]-8-oxo-7,8-dihydro-9H-purin-9-yl}-1-pyrrolidinecarboxylate The compound (5.2 g) prepared in Example 65 was dissolved in THF (52 mL), CDI (3.8 g) and DBU (1.7 mL) were added, and the mixture was stirred at room temperature for 1 hour. Saturated aqueous ammonium chloride was added to the reaction mixture, which was then diluted with ethyl acetate. The resulting organic layer was washed with saturated aqueous ammonium chloride and saturated brine, and concentrated under reduced pressure to give the title compound (6.0 g) having the following physical properties: LC-MS(A) retention time (min): 1.18; MS(ESI, Pos.): 474 (M + H) + ; 1 H-NMR(CDCl3):δ 1.49, 2.22-2.36, 2.75-2.94, 3.42-3.58, 3.73-3.87, 3.89-3.96, 3.97, 5.12-5.22, 7.63, 8.21-8.27. Reference example 67 4-{2-chloro-9-[(3S)-1-{[(2-methyl-2-propanyl)oxy]carbonyl}-3-pyrrolidinyl]-8-oxo-8,9-dihydro-7H-purin-7-yl}benzoic acid The same procedure as in Reference Example 6 was carried out using the compound (400 mg) prepared in Reference Example 66 instead of the compound prepared in Reference Example 5 to give the title compound (420 mg) having the following physical properties. LC-MS(A) retention time (min): 1.08; MS(ESI, Pos.): 460 (M + H) + . Reference example 68 2-Methyl-2-propanyl (3S)-3-[2-chloro-7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-pyrrolidinecarboxylate The same procedure as in Reference Example 54 was carried out using the compound prepared in Reference Example 67 instead of the compound prepared in Reference Example 6 to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.21; MS(ESI, Pos.): 748 (M + H) + ; 1 H-NMR(CDCl3):δ 1.46-1.52, 2.31, 2.85-2.97, 3.50, 3.75-4.10, 4.45-4.91, 5.19, 5.40-5.66, 6.89-6.97, 7.14, 7.27-7.35, 7.42, 7.46-7.58, 7.61-7.73, 7.85, 8.20, 8.31. Reference example 69 2-Methyl-2-propanyl (3S)-3-[7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-7,8-dihydro-9H-purin-9-yl]-1-pyrrolidinecarboxylate The same procedure as in Reference Example 62 was carried out using the compound prepared in Reference Example 68 instead of the compound prepared in Reference Example 61 to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.30; MS(ESI, Pos.): 889 (M + H) + . Reference example 70 3-Fluoro-4-({7-[4-(8-oxo-9-[(3S)-3-pyrrolidinyl]-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)benzoyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile The compound prepared in Reference Example 69 (356 mg) was dissolved in methanol (4.0 mL), and a 4N hydrogen chloride / 1,4-dioxane solution (1.0 mL) was added, followed by stirring at room temperature for 4 hours. The reaction mixture was neutralized with saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with saturated brine and then concentrated under reduced pressure to give the title compound (300 mg) having the following physical properties: LC-MS(A) retention time (min): 1.08; MS(ESI, Pos.): 789 (M + H) + . Example 25 3-Fluoro-4-({7-[4-(9-[(3S)-1-(methylsulfonyl)-3-pyrrolidinyl]-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)benzoyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile trifluoroacetate The compound (15 mg) prepared in Reference Example 70 was dissolved in DMF (0.15 mL), and DIPEA (0.010 mL) and methanesulfonic anhydride (4.0 mg) were added and stirred at room temperature for 1 hour. The reaction solution was purified by reverse-phase HPLC column to give the title compound (11 mg) having the following physical properties. LC-MS(A) retention time (min): 1.28; MS(ESI, Pos.): 867 (M + H) + ; 1 H-NMR(DMSO-d6):δ 2.29-2.41, 2.68-2.82, 2.82-2.93, 3.01, 3.38-3.51, 3.65-3.80, 3.80-3.88, 4.47-4.93, 5.15-5.30, 5.38-5.75, 6.66-7.08, 7.09-7.19, 7.31, 7.36-7.82, 7.85-8.00, 8.17-8.34, 9.79. Example 26 3-Fluoro-4-({7-[4-(8-oxo-9-[(3S)-1-(3,3,3-trifluoro-2,2-dimethylpropyl)-3-pyrrolidinyl]-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)benzoyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile 2-trifluoroacetate The compound prepared in Reference Example 70 (15 mg) was dissolved in DMF (0.15 mL), and 3,3,3-trifluoro-2,2-dimethylpropyl trifluoromethanesulfonate (26 mg) and DIPEA (0.033 mL) were added, followed by stirring at 60°C for 17 hours. The reaction mixture was cooled to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was concentrated, and the resulting residue was purified using a reverse-phase HPLC column to give the title compound (4.9 mg) having the following physical properties. LC-MS(A) retention time (min): 1.15; MS(ESI, Pos.): 913 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.20-1.37, 2.81-2.94, 3.60-4.05, 4.51-4.95, 4.98-5.31, 5.34-5.77, 6.96-7.25, 7.27-7.37, 7.41-7.80, 7.80-7.91, 7.91-8.05, 8.18-8.40, 9.62-9.84. Reference example 71 2-Methyl-2-propanyl 9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate 2-Methyl-2-propanyl 5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate (CAS: 1354801-07-2, 5.0 g) and 1-(bromomethyl)-4-chloro-2-fluorobenzene (3.1 mL) were dissolved in DMF (50 mL). The reaction mixture was ice-cooled, and sodium hydride (60% paraffin oil suspension, 878 mg) was added and stirred for 1 hour. Saturated aqueous ammonium chloride was added to the reaction mixture, followed by stirring and extraction with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexane:ethyl acetate = 9:1) to give the title compound (6.9 g) with the following physical properties. TLC: Rf 0.18 (hexane:ethyl acetate=9:1); 1H-NMR (CDCl3): δ 1.47, 2.79, 3.74, 4.52, 5.45, 6.74-6.93, 6.94-7.01, 7.05-7.14, 7.80, 8.28. Reference example 72 9-(4-chloro-2-fluorobenzyl)-6,7,8,9-tetrahydro-5H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine dihydrochloride The compound (6.9 g) prepared in Reference Example 71 was dissolved in methanol (20 mL), and a 4N hydrogen chloride / 1,4-dioxane solution (42 mL) was added and stirred at room temperature for 1 hour. The reaction mixture was concentrated, azeotroped with toluene, and filtered using MTBE to give the title compound (6.6 g) having the following physical properties: TLC: Rf 0.38 (dichloromethane:methanol=9:1); 1 H-NMR (DMSO-d6): δ 2.98, 3.41-3.51, 4.36, 5.52, 6.97, 7.15-7.22, 7.49, 8.01, 8.27, 9.72. Reference example 73 2-Methyl-2-propanyl 4-[2-chloro-7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinecarboxylate The same procedure as in Reference Example 7 was carried out using the compound (1.1 g) prepared in Reference Example 72 instead of the compound prepared in Reference Example 2 to give the title compound (1.9 g) having the following physical properties. LC-MS(A) retention time (min): 1.30; MS(ESI, Pos.): 785 (M + H) + . Reference example 74 2-chloro-7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one The same procedures as in Reference Example 55→Reference Example 56 were carried out using the compound prepared in Reference Example 73 instead of the compound prepared in Reference Example 54 to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.09; MS(ESI, Pos.): 755 (M + H) + . Example 27 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-{[4-(difluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one

[0473] [ka]

[0474] The same procedure as in Example 1 was carried out using the compound prepared in Reference Example 74 instead of the compound prepared in Reference Example 9 and 4-(difluoromethoxy)aniline instead of aniline to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.11; MS(ESI, Pos.): 878 (M + H) + ; 1 H-NMR (CDCl3):δ 0.96, 1.70-1.80, 2.03, 2.14, 2.45, 2.75-2.86, 2.87-3.05, 3.72-4.10, 4.30-4.42, 4.50-4.92, 5.23-5.60, 6.24-6.67, 6.81-6.91, 6.95-7.04, 7.09-7.18, 7.40-7.65, 7.65-7.71, 7.83, 8.32. Example 27-1 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one

[0475] [ka]

[0476] The same procedure as in Example 27 was carried out using 3-fluoroaniline instead of 4-(difluoromethoxy)aniline to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.15; MS(ESI, Pos.): 830 (M + H) + ; 1H-NMR(CDCl3):δ 0.93, 1.69-1.80, 2.05, 2.14, 2.45, 2.71-2.85, 2.85-3.02, 3.65-4.18, 4.29-4.43, 4.49-4.93, 5.20-5.60, 6.67-6.75, 6.80-7.03, 7.04-7.08, 7.08-7.17, 7.27-7.36, 7.41-7.69, 7.83, 8.32. Example 28 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-[(cyclopentylmethyl)(2-hydroxy-2-methylpropyl)amino]-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate The compound prepared in Reference Example 74 (50 mg) and 1-[(cyclopentylmethyl)amino]-2-methyl-2-propanol (57 mg) were dissolved in DMSO (0.5 mL), DIPEA (0.057 mL) and cesium fluoride (50 mg) were added, and the mixture was stirred using a microwave device at 100°C for 30 minutes and then at 120°C for 4 hours. The reaction mixture was cooled to room temperature, and insoluble matter was removed. The title compound (11 mg) having the following physical properties was obtained by purifying the reaction mixture using a reverse-phase HPLC column. LC-MS(A) retention time (min): 1.11; MS(ESI, Pos.): 890 (M + H) + ; 1 H-NMR(CDCl3):δ 1.13-1.22, 1.24-1.40, 1.50-1.63, 1.63-1.79, 2.02-2.08, 2.08-2.33, 2.84-3.09, 3.39-3.53, 3.63-3.85, 3.91-4.16, 4.50-4.64, 4.67-4.93, 5.29-5.63, 6.83-6.93, 6.95-7.04, 7.09-7.17, 7.22, 7.38-7.70, 7.96, 8.40. Example 28-1 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-(cyclohexylamino)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one 2-trifluoroacetate The same procedure as in Example 28 was carried out using cyclohexylamine instead of 1-[(cyclopentylmethyl)amino]-2-methyl-2-propanol to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.03; MS(ESI, Pos.): 818 (M + H) + ; 1 H-NMR(DMSO-d6):δ 1.03-1.13, 1.13-1.40, 1.48-1.68, 1.68-1.92, 1.92-2.07, 2.78-2.98, 3.02-3.12, 3.16-3.26, 3.73-4.06, 4.40-4.91, 5.19-5.66, 6.63-6.86, 6.86-7.37, 7.37-7.75, 7.82-8.06, 8.16-8.30, 8.61-8.98. Reference example 75 1-({4-[2-chloro-7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl]-1-piperidinyl}carbonyl)cyclopropanecarbonitrile The compound (1.9 g) prepared in Reference Example 73 was suspended in methanol (19 mL), and a 4N hydrogen chloride / 1,4-dioxane solution (6.0 mL) was added. The mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated, and a portion of the resulting residue (30 mg) was dissolved in DMF (0.6 mL). 1-Cyanocyclopropanecarboxylic acid (6.9 mg), DIPEA (0.036 mL), and DMTMM (34 mg) were added and stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was passed through an injection column (Amino) and concentrated to give the title compound (30 mg) with the following physical properties. LC-MS(A) retention time (min): 1.18; MS(ESI, Pos.): 778 (M + H) + . Example 29 1-[(4-{7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-[(3-fluorophenyl)amino]-6-methyl-8-oxo-7,8-dihydro-9H-purin-9-yl}-1-piperidinyl)carbonyl]cyclopropanecarbonitrile The same procedure as in Example 1 was carried out using the compound prepared in Reference Example 75 instead of the compound prepared in Reference Example 9 and 3-fluoroaniline instead of aniline to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 1.18; MS(ESI, Pos.): 853 (M + H) + ; 1H-NMR(CDCl3):δ 1.61-1.68, 1.94-2.04, 2.06, 2.62-3.10, 3.26-3.48, 3.73-4.16, 4.54-4.94, 5.23-5.63, 6.71, 6.82-6.91, 6.95-7.03, 7.07-7.17, 7.40-7.54, 7.61-7.71, 7.83, 8.32. Reference example 76 2-Methyl-2-propanyl 9-[2-fluoro-4-(trifluoromethyl)benzyl]-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine-7-carboxylate The same procedure as in Reference Example 1 was carried out using 1-(bromomethyl)-2-fluoro-4-(trifluoromethyl)benzene instead of 1-(bromomethyl)-2,4-difluorobenzene to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.28; MS(ESI, Pos.): 450 (M + H) + . Reference example 77 9-[2-Fluoro-4-(trifluoromethyl)benzyl]-6,7,8,9-tetrahydro-5H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridine dihydrochloride The same procedure as in Reference Example 2 was carried out using the compound prepared in Reference Example 76 instead of the compound prepared in Reference Example 1 to obtain the title compound having the following physical properties. LC-MS(A) retention time (min): 0.90; MS(ESI, Pos.): 350 (M + H) + ; 1 H-NMR (DMSO-d6): δ 2.99, 3.46, 4.38, 5.62, 7.06, 7.18, 7.49, 7.75, 8.02, 8.27, 9.72. Reference example 78 Methyl 4-{2-chloro-8-oxo-9-[(3S)-3-pyrrolidinyl]-8,9-dihydro-7H-purin-7-yl}benzoate monohydrochloride The compound (3.0 g) prepared in Reference Example 66 was suspended in methanol (63 mL), and a 4N solution of hydrogen chloride in 1,4-dioxane (23 mL) was added, followed by stirring overnight at room temperature. The reaction mixture was concentrated to give the title compound (2.6 g) having the following physical properties: LC-MS(A) retention time (min): 0.81; MS(ESI, Pos.): 374 (M + H) + . Reference example 79 Methyl 4-{2-chloro-8-oxo-9-[(3S)-1-{[1-(trifluoromethyl)cyclopropyl]methyl}-3-pyrrolidinyl]-8,9-dihydro-7H-purin-7-yl}benzoate The compound (700 mg) prepared in Reference Example 78 was dissolved in DMA (17 mL), and 1-(bromomethyl)-1-(trifluoromethyl)cyclopropane (692 mg), DIPEA (1.5 mL), and potassium iodide (283 mg) were added, followed by stirring overnight at 50°C. Saturated aqueous ammonium chloride solution was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate. The residue obtained after concentration under reduced pressure was purified by silica gel chromatography (hexane:ethyl acetate = 3:2 → 2:3) to give the title compound (500 mg) having the following physical properties. LC-MS(A) retention time (min): 0.91; MS(ESI, Pos.): 496 (M + H) + ; 1 H-NMR(CDCl3):δ 0.60-0.75, 0.96-1.05, 2.28-2.45, 2.70-2.89, 3.09, 3.30, 3.93-3.98, 5.17-5.27, 7.62-7.66, 8.20, 8.22-8.28. Reference example 80 Methyl 4-(8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-9-[(3S)-1-{[1-(trifluoromethyl)cyclopropyl]methyl}-3-pyrrolidinyl]-8,9-dihydro-7H-purin-7-yl)benzoate The same procedure as in Reference Example 62 was carried out using the compound prepared in Reference Example 79 instead of the compound prepared in Reference Example 61 to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.11; MS(ESI, Pos.): 637 (M + H) + . Reference example 81 4-(8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-9-[(3S)-1-{[1-(trifluoromethyl)cyclopropyl]methyl}-3-pyrrolidinyl]-8,9-dihydro-7H-purin-7-yl)benzoic acid The same procedure as in Reference Example 36 was carried out using the compound prepared in Reference Example 80 instead of the compound prepared in Reference Example 35 to give the title compound having the following physical properties. LC-MS(A) retention time (min): 1.03; MS(ESI, Pos.): 623 (M + H) + . Example 30 7-[4-({9-[2-fluoro-4-(trifluoromethyl)benzyl]-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-...

Claims

1. General formula (I) 【Chemistry 1】 (In the formula, R １ (1) 1 to 5 R １１ (2) methylene substituted with a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R １２ (3) methylene substituted with a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R １３ (4) methylene substituted with a C2-4 alkenyl group optionally substituted with 1 to 5 R １４ represents a methylene substituted by a C2-4 alkynyl group which may be substituted by R １１ , R １２ , R １３ and R １４ each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, or (6) a cyano group; １１ , R １２ , R １３ and R １４ may be the same or different, R ２ (1) 1 to 5 R １５ (2) a 3- to 15-membered heterocycle optionally substituted with 1 to 5 R １６ or (3) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R １７ represents a C1-4 alkyl group optionally substituted by R １５ , R １６ and R １７ are each independently (1) 1 to 5 R １８ (1) a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with (C1-8 alkyl)carbonyl group; (2) a C1-8 alkyl group optionally substituted with a C3-6 cycloalkyl group optionally substituted with (C1-8 alkyl)carbonyl group; (3) 1 to 5 R １９ (4) a C1-8 haloalkyl group, (5) a 5- or 6-membered carbocyclic ring, (6) a 5- or 6-membered heterocyclic ring, (7) a C1-4 alkylsulfonyl group, (8) a C2-4 alkenylsulfonyl group, (9) a C1-4 alkoxycarbonyl group, (10) a C1-4 haloalkylamino group, (11) a t-butyloxycarbonylamino group, or (12) a 5,5-dimethyl-2,4-dioxooxazolidin-3-yl group; Multiple R １５ , R １６ and R １７ may be the same or different, R １８ and R １９ each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, or (6) a cyano group; Multiple R １８ and R １９ may be the same or different, R ３ is (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, (6) a C1-4 haloalkoxy group, (7) a cyano group, or (8) 1 to 5 R ２０ (9) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R ２１ (10) a 3- to 15-membered heterocycle optionally substituted with —NR ２２ R ２３ , (11)-OR ２４ , (12)-CONR ２５ R ２６ (13) a (C1-8 alkyl)carbonyl group, (14) a C1-4 alkyl group substituted with 1 to 3 hydroxyl groups, or (15) a 1-(hydroxyimino)ethyl group; R ２０ and R ２１ are each independently: (1) 1 to 5 R ２７ (2) a C1-4 alkyl group optionally substituted with one to five R ２８ (4) a C3-6 cycloalkyl group optionally substituted with 1 to 5 R ２７-1 (5) a C1-4 alkoxy group optionally substituted with (4), (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R ２０ and R ２１ may be the same or different, R ２７ , R ２７-1 and R ２８ each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R ２７ , R ２７-1 and R ２８ may be the same or different, R ２２ , R ２３ and R ２４ are each independently (1) a hydrogen atom, (2) 1 to 5 R ２９ (3) a C1-8 alkyl group optionally substituted with 1 to 5 R ２９－１ (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R ２９－２ (5) a C2-4 alkynyl group optionally substituted with 1 to 5 R ３０ or (6) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R ３１ represents a 3- to 15-membered heterocycle optionally substituted by R ２９ , R ２９－１ , R ２９－２ , R ３０ and R ３１ are each independently (1) 1 to 5 R ３２ (2) a C1-4 alkyl group optionally substituted with one to five R ３３ (4) a C3-8 cycloalkyl group optionally substituted with 1 to 5 R ３４ (5) a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R ３５ (6) a 5- to 6-membered heterocycle optionally substituted with 1 to 5 R ３２-1 (7) a C1-4 alkoxy group optionally substituted with (4), (8) a hydroxyl group, (9) a carbamoyl group, or (10) a cyano group; Multiple R ２９ , R ２９－１ , R ２９－２ , R ３０ and R ３１ may be the same or different, R ３２ , R ３２－１ , R ３３ , R ３４ and R ３５ each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, (7) a carbamoyl group, (8) a carboxyl group, or (9) a cyano group; Multiple R ３２ , R ３２－１ , R ３３ , R ３４ and R ３５ may be the same or different, R ２５ and R ２６ are each independently (1) a hydrogen atom, (2) 1 to 5 R ３６ (3) a C1-8 alkyl group optionally substituted with 1 to 5 R ３６－１ (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R ３６－２ (5) a C2-4 alkynyl group optionally substituted with 1 to 5 R ３７ or (6) a 3- to 15-membered carbocyclic ring optionally substituted with 1 to 5 R ３８ represents a 3- to 15-membered heterocycle optionally substituted by R ３６ , R ３６－１ , R ３６－２ , R ３７ and R ３８ each independently represents (1) a C1-4 alkyl group, (2) a halogen, (3) a C3-8 cycloalkyl group, (4) a 5- or 6-membered carbocyclic ring, (5) a 5- or 6-membered heterocyclic ring, (6) a C1-4 alkoxy group, (7) a C1-4 haloalkyl group, (8) a C1-4 haloalkoxy group, (9) a hydroxyl group, (10) a carboxyl group, (11) a carbamoyl group, or (12) a cyano group; Multiple R ３６ , R ３６－１ , R ３６－２ , R ３７ and R ３８ may be the same or different, R ４ represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; R ５ represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; X is a nitrogen atom or CR ７ represents X １ , X ２ , and X ３ are each independently a nitrogen atom, CH, or CR ６ represents R ６ represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, (5) a C1-4 haloalkoxy group, (6) a hydroxyl group, or (7) a cyano group; R ６ If there are multiple R ６ may be the same or different, Y １ is a nitrogen atom, or CR ８ represents Y ２ is a nitrogen atom, or CR ９ represents Y ３ is a nitrogen atom, or CR １０ represents R ７ represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R ８ represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R ９ represents (1) a hydrogen atom, (2) a halogen, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, or (6) a C1-4 haloalkoxy group; R １０ represents (1) a hydrogen atom, (2) a halogen atom, (3) a C1-4 alkyl group, (4) a C1-4 alkoxy group, (5) a C1-4 haloalkyl group, (6) a C1-4 haloalkoxy group, (7) a hydroxyl group, (8) an amino group, (9) a carboxyl group, (10) a carbamoyl group, (11) a (C1-4 alkyl)aminocarbonyl group, (12) a di-(C1-4 alkyl)aminocarbonyl group, (13) -CO- (a 3- to 6-membered saturated heterocycle), or (14) -CONHR ３９ or (15) a cyano group; R ３９ is (1) a C1-4 alkyl group substituted with a cyano group, (2) a C1-4 alkoxy group, (3) a C1-4 haloalkyl group, (4) a C1-4 haloalkoxy group, (5) a hydroxyl group, (6) an amino group, (7) a (C1-4 alkyl)amino group, (8) a di-(C1-4 alkyl)amino group, or (9) 1 to 5 R ４０ or (10) 1 to 5 R ４１ represents a 3- to 6-membered saturated heterocyclic ring optionally substituted by R ４０ and R ４１ each independently represents (1) a halogen, (2) a C1-4 alkyl group, (3) a C1-4 alkoxy group, (4) a C1-4 haloalkyl group, or (5) a C1-4 haloalkoxy group; Multiple R ４０ and R ４１ may be the same or different, r represents an integer of 0 to 3, and a plurality of R ４ may be the same or different, s represents an integer of 0 to 3, and a plurality of R ５ may be the same or different. wherein each hydrogen atom may be a deuterium atom or a tritium atom.) or a salt thereof.

2. General formula (I-1) 【Chemistry 2】 2. The compound according to claim 1, represented by the formula: (wherein t represents an integer of 0 to 3, and other symbols have the same meanings as in claim 1), or a salt thereof.

3. R ２ But 1 to 5 R １５ 3. The compound according to claim 1 or 2, wherein the compound is a 5- to 7-membered nitrogen-containing saturated heterocycle optionally substituted by:

4. R １ But 1 to 5 R １１ 4. The compound according to claim 1, wherein methylene is substituted with a 5- or 6-membered carbocyclic ring optionally substituted with: or a salt thereof.

5. R ３ (1) 1 to 5 R ２０ (2) a 5- to 6-membered carbocyclic ring or indane optionally substituted with 1 to 5 R ２１ or (3) a 5- to 6-membered heterocycle optionally substituted with —NR ２２ R ２３ The compound according to any one of claims 1 to 4, or a salt thereof,

6. General formula (I-1-1) 【Transformation 3】 (In the formula, R １－１ is 1 to 5 R １１ ring1 represents a 5- to 7-membered nitrogen-containing saturated heterocycle; R ３－１ (1) Each of the R ２０ (2) a 5- to 6-membered carbocyclic ring or indane optionally substituted with 1 to 5 R ２１ or (3) a 5- to 6-membered heterocycle optionally substituted with —NR ２２ R ２３ represents R １５－１ is 1 to 5 R １８ wherein u represents an integer of 0 to 2, and the other symbols have the same meanings as in claim 1.) or a salt thereof.

7. General formula (I-1-1-1) 【Chemistry 4】 (Wherein, ring 2 is (1) 1 to 5 R ２０ (2) a 5- to 6-membered carbocyclic ring or indane, optionally substituted with 1 to 5 R ２１ The compound according to claim 6, represented by the formula: wherein R represents a 5- or 6-membered heterocycle optionally substituted by R, and the other symbols have the same meanings as in claims 1 and 6, or a salt thereof.

8. The compound is (1) 1-(3-{7-(4-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)cyclopropanecarboxylic acid; (2) 2-(3-{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}phenyl)-2-methylpropanoic acid, or (3) The compound according to claim 7, which is 4-({7-[(5-{9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-2-[2-methyl-4-(trifluoromethoxy)phenyl]-8-oxo-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)-3-fluorobenzonitrile, or a salt thereof.

9. General formula (I-1-1-2) 【Transformation 5】 (Wherein, ring 3 is 1 to 5 R ３０ a 5- to 6-membered carbocyclic ring optionally substituted with 1 to 5 R ３１ represents a 5- to 6-membered heterocycle optionally substituted by ２３－１ is (1) a hydrogen atom, (2) 1 to 5 R ２９ (3) a C1-8 alkyl group optionally substituted with 1 to 5 R ２９－１ or (4) a C2-4 alkenyl group optionally substituted with 1 to 5 R ２９－２ The compound according to claim 6, represented by the formula: wherein R represents an optionally substituted C2-4 alkynyl group, and the other symbols have the same meanings as in claims 1 and 6, or a salt thereof.

10. The compound is (1) 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-2-{[4-(difluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-7,9-dihydro-8H-purin-8-one; (2) 7-(4-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}phenyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, (3) 9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-7-(6-{[9-(2-fluoro-4-methylbenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-6-methyl-2-{[4-(trifluoromethoxy)phenyl]amino}-7,9-dihydro-8H-purin-8-one, (4) 4-[(7-{[5-(9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-2-{[4-(trifluoromethoxy)phenyl]amino}-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, (5) 3-fluoro-4-({7-[(5-{2-[(3-fluorophenyl)amino]-6-methyl-8-oxo-9-(1-{[1-(trifluoromethyl)cyclopropyl]methyl}-4-piperidinyl)-8,9-dihydro-7H-purin-7-yl}-2-pyridinyl)carbonyl]-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl}methyl)benzonitrile, (6) 4-[(7-{[5-(2-{[2-chloro-4-(trifluoromethoxy)phenyl]amino}-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-7-yl)-2-pyridinyl]carbonyl}-5,6,7,8-tetrahydro-9H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-9-yl)methyl]-3-fluorobenzonitrile, or (7) The compound according to claim 9, which is 7-(6-{[9-(4-chloro-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-2-[(3-fluorophenyl)amino]-6-methyl-7,9-dihydro-8H-purin-8-one, or a salt thereof.

11. General formula (I-1-1-3) 【Transformation 6】 7. The compound according to claim 6, which is represented by the formula: (wherein all symbols have the same meanings as in claims 1, 6 and 9), or a salt thereof.

12. The compound according to claim 11, wherein the compound is (1) 1-{[{7-(6-{[9-(4-cyano-2-fluorobenzyl)-5,6,8,9-tetrahydro-7H-pyrido[4',3':4,5]pyrrolo[2,3-b]pyridin-7-yl]carbonyl}-3-pyridinyl)-9-[1-(2,2-dimethylpropyl)-4-piperidinyl]-6-methyl-8-oxo-8,9-dihydro-7H-purin-2-yl}(cyclohexyl)amino]methyl}cyclobutanecarboxylic acid, or a salt thereof.

13. A pharmaceutical composition comprising the compound represented by formula (I) according to claim 1 or a salt thereof and a pharmaceutically acceptable carrier.

14. The pharmaceutical composition according to claim 13, which is a DGKα and / or DGKζ inhibitor.

15. The pharmaceutical composition according to claim 13 or 14, which is an agent for inhibiting the progression, inhibiting the recurrence and / or treating a DGKα and / or DGKζ-associated disease.

16. The pharmaceutical composition according to claim 15, wherein the DGKα and / or DGKζ-associated disease is cancer or an infectious disease.

17. 17. The pharmaceutical composition according to claim 16, wherein the cancer is a solid cancer or a blood cancer.

18. 18. The pharmaceutical composition according to claim 17, wherein the solid cancer is one or more cancers selected from malignant melanoma, non-small cell lung cancer, small cell lung cancer, head and neck cancer, renal cell carcinoma, breast cancer, ovarian cancer, ovarian clear cell adenocarcinoma, nasopharyngeal carcinoma, uterine cancer, anal cancer, colorectal cancer, rectal cancer, colon cancer, hepatocellular carcinoma, esophageal cancer, gastric cancer, esophagogastric junction cancer, pancreatic cancer, urothelial cancer, prostate cancer, fallopian tube cancer, primary peritoneal cancer, malignant pleural mesothelioma, gallbladder cancer, bile duct cancer, biliary tract cancer, skin cancer, testicular cancer (germ cell tumor), vaginal cancer, vulvar cancer, penile cancer, small intestine cancer, endocrine system cancer, thyroid cancer, parathyroid cancer, adrenal cancer, spinal tumor, neuroblastoma, medulloblastoma, ocular retinoblastoma, neuroendocrine tumor, brain tumor, and squamous cell carcinoma.

19. 18. The pharmaceutical composition according to claim 17, wherein the solid cancer is bone and soft tissue sarcoma or Kaposi's sarcoma.

20. 18. The pharmaceutical composition according to claim 17, wherein the blood cancer is one or more cancers selected from multiple myeloma, malignant lymphoma, leukemia, myelodysplastic syndrome, and myeloproliferative disorder.

21. 10. An agent for inhibiting the progression, inhibiting recurrence and / or treating a DGKα and / or DGKζ-associated disease, comprising the compound represented by general formula (I) according to claim 1 or a salt thereof.

22. A method for inhibiting the progression, inhibiting recurrence and / or treating a DGKα and / or DGKζ-associated disease, which comprises administering to a mammal an effective amount of a compound represented by general formula (I) according to claim 1 or a salt thereof.

23. 2. The compound represented by formula (I) according to claim 1, or a salt thereof, for use in inhibiting the progression, inhibiting recurrence and / or treating DGKα and / or DGKζ-associated diseases.

24. 10. Use of a compound represented by formula (I) according to claim 1 or a salt thereof for the manufacture of an agent for inhibiting the progression, inhibiting recurrence and / or treating a DGKα and / or DGKζ-associated disease.

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