Fused ring compounds that inhibit H-PGDS

Abstract

The present invention provides: compounds that have an inhibitory activity on hematopoietic prostaglandin D synthase (H-PGDS) and are useful for the prevention or treatment of diseases in which the synthase is implicated; and drug compositions that contain the compounds. In specific terms, the present invention provides compounds given by formula (I) or a pharmaceutically acceptable salt thereof. [In formula (I), R1 represents a hydrogen atom, etc.; R2 represents a hydrogen atom, etc.; R3 represents a hydrogen atom, etc.; R4 represents a hydrogen atom, etc.; R5 represents a hydrogen atom, etc.; W represents an oxygen atom, etc.; and X represents a C1-6 alkyl group, etc.]

Description

[Technical Field]

[0001] The present invention relates to fused ring compounds that inhibit H-PGDS and are useful in the pharmaceutical field. Specifically, the present invention relates to fused ring compounds that have hematopoietic prostaglandin D synthase inhibitory activity and are useful for the prevention and treatment of diseases associated with the enzyme, pharmaceutical compositions containing the compounds, and inhibitors of the enzyme. [Background technology]

[0002] Prostaglandin D synthase is an enzyme that converts prostaglandin H2, a common intermediate of various prostaglandins, to prostaglandin D2. Hematopoietic prostaglandin D synthase (H-PGDS), which is distributed in mast cells and Th2 lymphocytes, is known to be involved in various diseases (e.g., allergic diseases, inflammatory diseases, neuromuscular disorders, ischemic diseases, etc.) through the production of prostaglandin D2. Therefore, attempts have been made to develop pharmaceutical compounds that treat the above-mentioned various diseases by inhibiting H-PGDS (Patent Documents 1 to 23 and Non-Patent Documents 1 to 3). [Prior art documents] [Patent documents]

[0003] [Patent Document 1] International Publication No. WO2019 / 203296 [Patent Document 2] Japanese Patent Application Laid-Open No. 2013-14520 [Patent Document 3] International Publication No. WO2012 / 033069 [Patent Document 4] International Publication No. WO2011 / 090062 [Patent Document 5] International Publication No. WO2010 / 104024 [Patent Document 6] International Publication No. WO2007 / 007778 [Patent Document 7] Japanese Patent Application Laid-Open No. 2007-51121 [Patent Document 8] International Publication No. WO2020 / 095215 [Patent Document 9] International Publication No. WO2019 / 116256 [Patent Document 10] International Publication No. WO2018 / 229629 [Patent Document 11] International Publication No. WO2018 / 069863 [Patent Document 12] International Publication No. WO2017 / 103851 [Patent Document 13] International Publication No. WO2011 / 044307 [Patent Document 14] International Publication No. WO2008 / 121670 [Patent Document 15] International Publication No. WO2007 / 041634 [Patent Document 16] International Publication No. WO2011 / 150457 [Patent Document 17] International Publication No. WO2010 / 033977 [Patent Document 18] International Publication No. WO2009 / 153721 [Patent Document 19] International Publication No. WO2009 / 153720 [Patent Document 20] International Publication No. WO2008 / 104869 [Patent Document 21] International Publication No. WO2008 / 075172 [Patent Document 22] International Publication No. WO2005 / 094805 [Patent Document 23] International Publication No. WO2017 / 209272 [Non-patent literature]

[0004] [Non-Patent Document 1] Bioorg.Med.Chem.Lett.2012,22,3795-3799 [Non-patent document 2] J.Med.Chem.2010,53,5536-5548 [Non-patent document 3] Bioorg.Med.Chem.Lett.2021,34,127759 Summary of the Invention [Problem to be solved by the invention]

[0005] An objective of the present invention is to provide novel fused ring compounds that have excellent H-PGDS inhibitory activity and are useful for treating or preventing diseases associated with H-PGDS. [Means for solving the problem]

[0006] In order to solve the above problems, the present inventors have extensively synthesized and investigated novel compounds, and as a result, have found that a fused ring compound represented by the following formula (I) has excellent H-PGDS inhibitory activity, thereby completing the present invention. Thus, the present invention provides a compound of formula (I): TIFF0007734129000001.tif2545 [In formula (I), R 1 is a hydrogen atom, a halogen atom or C 1-6 represents an alkyl group; R 2 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, a carbamoyl group, C 1-6 Alkyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 Alkyl group or C 1-6 represents an alkoxy group; R 3 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl group, C 2-7Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl)C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkylsulfonylamino group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, C 3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, or a halocyclic amino group; R 4 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, mono C 1-6 Alkylamino group or diC 1-6 represents an alkylamino group; R 5 is a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, C 1-6 Alkyl group, halo C 1-6 Alkyl or hydroxy C 1-6 represents an alkyl group; W is an oxygen atom, a sulfur atom, or a group represented by the general formula: -N(R 6 )- represents a group represented by; R 6 is a hydrogen atom or C 1-6 represents an alkyl group; X is C1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group, (haloC 1-6 Alkoxy)C 1-6 Alkyl group, amino C 1-6 Alkyl group, (mono C 1-6 Alkylamino)C 1-6 Alkyl group, (diC 1-6 Alkylamino)C 1-6 Alkyl group, carbamoyl C 1-6 Alkyl group, (mono C 1-6 Alkylcarbamoyl)C 1-6 Alkyl group, (diC 1-6 Alkylcarbamoyl)C 1-6 Alkyl group, sulfamoyl C 1-6 Alkyl group, (mono C 1-6 Alkyl sulfamoyl)C 1-6 Alkyl group, (diC 1-6 Alkyl sulfamoyl)C 1-6 an alkyl group, or General formula (II): TIFF0007734129000002.tif2561(in the formula, The wavy line represents the point of attachment to the nitrogen atom; L 1 is a single bond, C 1-6 Alkanediyl group or hydroxy C 1-6 represents an alkanediyl group; Ring Y is C 6-10 Aryl groups, heteroaryl groups, C 3-10 represents a cycloalkyl group or a 4- to 10-membered heterocyclyl group (wherein the C 3-10 The cycloalkyl group and the 4- to 10-membered heterocyclyl group may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may form a bicyclo or spiro ring group; R 7are each independently a halogen atom, a cyano group, a hydroxy group, a sulfanyl group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, a formyl group, an imino group, an azido group, a hydrazino group, a nitro group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group, C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, hydroxy C 1-6 Alkoxy group, C 1-6 Alkylthio group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, mono(haloC 1-6 alkyl)amino group, C 2-7 Alkoxycarbonyl group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl)C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkyl sulfonyl amino group, mono(C 2-7 Alkoxycarbonyl)amino group, C 3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, a halocyclic amino group, or an oxo group; L 2 is a single bond, C 1-6 Alkanediyl group, hydroxy C 1-6 represents an alkanediyl group, a carbonyl group, or a sulfonyl group; Ring Z represents a phenyl group, a heteroaryl group, or a 4- to 10-membered heterocyclyl group (the 4- to 10-membered heterocyclyl group may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may form a bicyclo ring group or a spiro ring group); R 8 are each independently a halogen atom, a cyano group, a hydroxy group, a sulfanyl group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group, C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, C 2-7 Alkoxycarbonyl group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl)C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkyl sulfonyl amino group, mono(C 2-7 Alkoxycarbonyl)amino group, C 3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, a halocyclic amino group, or an oxo group; m represents 0, 1, 2 or 3; n represents 0, 1, or 2; and p is a group represented by the formula: or a pharmaceutically acceptable salt thereof (hereinafter also referred to as "the compound of the present invention"). Furthermore, the compounds of the present invention include those having the formula (I) where R 7 is an oxetanylamino group, hydroxyhalo C 1-6 Alkyl group, halo C 2-7 Alkanoyl group, hydroxy C 2-7 Alkanoyl group, hydroxy C 3-6 Cycloalkyl groups, (hydroxy C 3-6 Cycloalkyl)C 1-6 Alkoxy group or C 3-6 is a cycloalkylcarbonyl group, R 8 Also included are compounds in which is a morpholinocarbonyl group.

[0007] Furthermore, the present invention relates to pharmaceutical compositions containing the compounds of the present invention, particularly pharmaceutical compositions for use in the treatment or prevention of diseases associated with H-PGDS. Furthermore, the present invention relates to an H-PGDS inhibitor containing the compound of the present invention. [Effects of the Invention]

[0008] As will be shown in the Examples below, the compounds of the present invention have excellent H-PGDS inhibitory activity and are therefore useful as therapeutic or preventive agents for diseases involving H-PGDS. DETAILED DESCRIPTION OF THE INVENTION

[0009] The definitions of the terms used to identify the compounds of the present invention are explained below.

[0010] The "halogen atom" in formula (I) (including formula (II) and formula (III) in formula (I), the same applies hereinafter) includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom.

[0011] "C" in formula (I) 1-6The term "alkyl group" means a straight-chain or branched alkyl group having 1 to 6 carbon atoms, and examples thereof include a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, a pentyl group, an isopentyl group, a neopentyl group, a 1,1-dimethylpropyl group, a 1-methylbutyl group, a 2-methylbutyl group, a 1,2-dimethylpropyl group, a 1-ethylpropyl group, a hexyl group, an isohexyl group, a 1-methylpentyl group, a 2-methylpentyl group, a 3-methylpentyl group, a 1,1-dimethylbutyl group, a 1,2-dimethylbutyl group, a 2,2-dimethylbutyl group, a 1,3-dimethylbutyl group, a 2,3-dimethylbutyl group, a 3,3-dimethylbutyl group, a 1-ethylbutyl group, a 2-ethylbutyl group, and a 1,2,2-trimethylpropyl group.

[0012] "HaloC" in formula (I) 1-6 The term "alkyl group" refers to the "C alkyl group" in which any substitutable position is substituted with one or more, preferably 1 to 5, identical or different "halogen atoms". 1-6 It means an "alkyl group," and examples thereof include a fluoromethyl group, a difluoromethyl group, a trifluoromethyl group, a 2-fluoroethyl group, a 1,2-difluoroethyl group, a 2,2,2-trifluoroethyl group, a 2,2,3,3,3-pentafluoropropyl group, a chloromethyl group, a 2-chloroethyl group, a 1,2-dichloroethyl group, a bromomethyl group, and an iodomethyl group.

[0013] "Hydroxy C" in formula (I) 1-6 The term "alkyl group" refers to the above-mentioned "C alkyl group" in which any substitutable position is substituted with one or more, preferably one or two, hydroxy groups. 1-6 It means an "alkyl group," and examples thereof include a hydroxymethyl group, a 1-hydroxyethyl group, a 1-hydroxypropyl group, a 2-hydroxyethyl group, a 2-hydroxypropyl group, a 2-hydroxy-1-methylethyl group, a 1-hydroxy-1-methylethyl group, a 1,2-dihydroxyethyl group, and a 3-hydroxypropyl group.

[0014] "HydroxyhaloC" in formula (I) 1-6The term "alkyl group" refers to the above-mentioned "halo C alkyl group" substituted with one or more, preferably one or two, hydroxy groups at any substitutable position. 1-6 Examples of the alkyl group include 2,2,2-trifluoro-1-hydroxyethyl and 2-hydroxy-1,1-difluoroethyl groups.

[0015] "C" in formula (I) 1-6 An "alkoxy group" is a group in which the hydrogen atom of a hydroxy group is substituted with one of the above "C 1-6 It means a group substituted with an "alkyl group," and examples thereof include a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a butoxy group, a sec-butoxy group, a tert-butoxy group, a pentyloxy group, an isopentyloxy group, a hexyloxy group, and an isohexyloxy group.

[0016] "C" in formula (I) 2-6 The term "alkenyl group" means a straight-chain or branched alkenyl group having 2 to 6 carbon atoms, and examples thereof include a vinyl group, a 1-propenyl group, an allyl group, an isopropenyl group, a 3-butenyl group, a 2-butenyl group, a 1-butenyl group, a 1-methyl-2-propenyl group, a 1-methyl-1-propenyl group, a 1-ethyl-1-ethenyl group, a 2-methyl-2-propenyl group, a 2-methyl-1-propenyl group, a 3-methyl-2-butenyl group, and a 4-pentenyl group.

[0017] "C" in formula (I) 2-7 The "alkanoyl group" refers to the group defined above as "C 1-6 It means a group in which an "alkyl group" is bonded to a carbonyl group, i.e., an alkanoyl group having 2 to 7 carbon atoms, and examples thereof include an acetyl group, a propanoyl group, a butanoyl group, a 2-methylpropanoyl group, a pentanoyl group, a 3-methylbutanoyl group, and a 2,2-dimethylpropanoyl group.

[0018] "HaloC" in formula (I) 2-7 The term "alkanoyl group" refers to the "C alkyl group" in which any substitutable position is substituted with one or more, preferably 1 to 5, of the same or different "halogen atoms". 2-7alkanoyl group, and examples thereof include 3,3,3-trifluoropropanoyl group.

[0019] "Hydroxy C" in formula (I) 2-7 The term "alkanoyl group" refers to the above-mentioned "C alkanoyl group" in which any substitutable position is substituted with one or more, preferably one or two, hydroxy groups. 2-7 alkanoyl group, and examples thereof include 2-hydroxy-2-methylpropanoyl group.

[0020] "C" in formula (I) 1-6 The "alkylsulfonyl group" is the same as the "C 1-6 It means a group in which an "alkyl group" and a sulfonyl group are bonded, and examples thereof include a methylsulfonyl group, an ethylsulfonyl group, a propylsulfonyl group, an isopropylsulfonyl group, a butylsulfonyl group, a sec-butylsulfonyl group, an isobutylsulfonyl group, a tert-butylsulfonyl group, a pentylsulfonyl group, an isopentylsulfonyl group, a hexylsulfonyl group, and an isohexylsulfonyl group.

[0021] "HaloC" in formula (I) 1-6 An "alkoxy group" is a group in which the hydrogen atom of a hydroxy group is substituted with one of the above-mentioned "halo C 1-6 "alkyl" refers to a group substituted with "alkyl group," and examples thereof include a fluoromethoxy group, a difluoromethoxy group, a trifluoromethoxy group, a 2-fluoroethoxy group, a 1,2-difluoroethoxy group, a 2,2,2-trifluoroethoxy group, a chloromethoxy group, a 2-chloroethoxy group, a 1,2-dichloroethoxy group, a bromomethoxy group, and an iodomethoxy group.

[0022] "C" in formula (I) 1-6 The term "alkylsulfonyloxy group" refers to a group in which the hydrogen atom of the hydroxy group is substituted with the alkyl group described above. 1-6 and the like. Examples of the substituted alkylsulfonyl group include a methylsulfonyloxy group, an ethylsulfonyloxy group, a propylsulfonyloxy group, and an isopropylsulfonyloxy group.

[0023] "HaloC" in formula (I)1-6 The term "alkylsulfonyloxy group" refers to the "C alkylsulfonyloxy group" in which any substitutable position is substituted with one or more, preferably one to three, of the same or different "halogen atoms". 1-6 alkylsulfonyloxy group," and examples thereof include a fluoromethylsulfonyloxy group, a difluoromethylsulfonyloxy group, a trifluoromethylsulfonyloxy group, and a 2,2,2-trifluoroethylsulfonyloxy group.

[0024] "Mono C" in formula (I) 1-6 The term "alkylamino group" refers to a group in which one hydrogen atom of the amino group is substituted with the above-mentioned "C 1-6 and examples thereof include methylamino group, ethylamino group, propylamino group, isopropylamino group, butylamino group, sec-butylamino group, and tert-butylamino group.

[0025] "DiC" in formula (I) 1-6 The term "alkylamino group" refers to an amino group in which two hydrogen atoms of the amino group are the same or different. 1-6 "N-methylamino" means a group substituted with "an alkyl group," and examples thereof include a dimethylamino group, a diethylamino group, a dipropylamino group, a diisopropylamino group, a dibutylamino group, a diisobutylamino group, a dipentylamino group, a dihexylamino group, an N-ethyl-N-methylamino group, an N-methyl-N-propylamino group, an N-butyl-N-methylamino group, an N-methyl-N-pentylamino group, and an N-hexyl-N-methylamino group.

[0026] "Mono C" in formula (I) 2-7 An "alkanoylamino group" refers to a group in which one hydrogen atom of the amino group is substituted with one of the above-mentioned "C 2-7 It means a group substituted with an "alkanoyl group", and examples thereof include an acetylamino group, a propanoylamino group, a butanoylamino group, a 2-methylpropanoylamino group, a pentanoylamino group, a 3-methylbutanoylamino group, and a 2,2-dimethylpropanoylamino group.

[0027] "(C 2-7Alkanoyl)C 1-6 The "mono C alkylamino group" is 1-6 The hydrogen atom bonded to the nitrogen atom of the "C alkylamino group" is 2-7 It means a group substituted with an "alkanoyl group", and examples thereof include an N-acetyl-N-methylamino group, an N-methyl-N-propanoylamino group, an N-butanoyl-N-methylamino group, an N-methyl-N-pentanoylamino group, an N-acetyl-N-ethylamino group, and an N-acetyl-N-propylamino group.

[0028] "DiC" in formula (I) 2-7 The term "alkanoylamino group" refers to an amino group in which two hydrogen atoms of the amino group are the same or different. 2-7 It means a group substituted with an "alkanoyl group", and examples thereof include a diacetylamino group, a dipropanoylamino group, and an N-acetyl-N-propanoylamino group.

[0029] "Mono C" in formula (I) 1-6 The term "alkylsulfonylamino group" refers to a group in which one hydrogen atom of the amino group is substituted with the above-mentioned "C 1-6 and the like.

[0030] "Mono C" in formula (I) 1-6 The term "alkylcarbamoyl group" refers to a carbamoyl group in which one hydrogen atom is substituted with the aforementioned "C 1-6 and examples thereof include methylcarbamoyl, ethylcarbamoyl, propylcarbamoyl, isopropylcarbamoyl, butylcarbamoyl, sec-butylcarbamoyl, and tert-butylcarbamoyl groups.

[0031] "DiC" in formula (I) 1-6 The term "alkylcarbamoyl group" refers to a carbamoyl group in which two hydrogen atoms are the same or different.1-6 and examples thereof include a dimethylcarbamoyl group, a diethylcarbamoyl group, a dipropylcarbamoyl group, a diisopropylcarbamoyl group, and an N-ethyl-N-methylcarbamoyl group.

[0032] "Mono C" in formula (I) 1-6 The term "alkylsulfamoyl group" refers to a group in which one hydrogen atom of the sulfamoyl group is substituted with the above-mentioned "C 1-6 and examples thereof include methylsulfamoyl, ethylsulfamoyl, propylsulfamoyl, isopropylsulfamoyl, butylsulfamoyl, sec-butylsulfamoyl, and tert-butylsulfamoyl groups.

[0033] "DiC" in formula (I) 1-6 The term "alkylsulfamoyl group" refers to a sulfamoyl group in which two hydrogen atoms are the same or different. 1-6 and examples thereof include a dimethylsulfamoyl group, a diethylsulfamoyl group, a dipropylsulfamoyl group, a diisopropylsulfamoyl group, and an N-ethyl-N-methylsulfamoyl group.

[0034] "C" in formula (I) 3-6 The term "cycloalkyl group" means a 3- to 6-membered aliphatic cyclic group, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.

[0035] "Hydroxy C" in formula (I) 3-6 The term "cycloalkyl group" refers to the above-mentioned "C cycloalkyl group" in which any substitutable position is substituted with one or more, preferably one or two, hydroxy groups. 3-6 It means a "cycloalkyl group" and includes, for example, a 1-hydroxycyclopropyl group, a 2-hydroxycyclopropyl group, and a 1-hydroxycyclobutyl group.

[0036] "(hydroxy C 3-6 Cycloalkyl)C 1-6The term "alkoxy group" refers to a group in which any substitutable position is one or more, preferably one of the above-mentioned "hydroxy C 3-6 The "C" substituted with "cycloalkyl group" 1-6 and examples thereof include a (1-hydroxycyclopropyl)methoxy group, a (2-hydroxycyclopropyl)methoxy group, and a (1-hydroxycyclobutyl)methoxy group.

[0037] "C" in formula (I) 3-6 The "cycloalkylcarbonyl group" means the "C 3-6 It means a group in which a "cycloalkyl" is bonded to a carbonyl group, and examples thereof include a cyclopropylcarbonyl group, a cyclobutylcarbonyl group, a cyclopentylcarbonyl group, and a cyclohexylcarbonyl group.

[0038] The "cyclic ether group" in formula (I) is the same as the "C 3-6 It means a group in which one or two carbon atoms constituting the ring of a "cycloalkyl group" are substituted with one or two oxygen atoms, and examples thereof include an oxiranyl group, an oxetanyl group, an oxolanyl group, a dioxolanyl group, an oxanyl group, and a dioxanyl group.

[0039] The "cyclic amino group" in formula (I) is the same as the "C 3-6 "Cycloalkyl group" means a group in which one or two carbon atoms constituting the ring of the cycloalkyl group are substituted with nitrogen atoms and the nitrogen atoms have a bond thereon, and examples thereof include azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, and piperazin-1-yl groups.

[0040] The "halocyclic amino group" in formula (I) means the "cyclic amino group" in which any substitutable position is substituted with one or more, preferably one to five, identical or different "halogen atoms" as defined above, and examples thereof include a 3-fluoroazetidin-1-yl group, a 3,3-difluoroazetidin-1-yl group, a 3,3-difluoropyrrolidin-1-yl group, a 3,3,4,4-tetrafluoropyrrolidin-1-yl group, and a 3,3-difluoropiperidin-1-yl group.

[0041] "(C 1-6 Alkoxy)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one or two, of the same or different "C 1-6 The "C" substituted with an "alkoxy group" 1-6 It means an "alkyl group," and examples thereof include a methoxymethyl group, an ethoxymethyl group, a 1-methoxyethyl group, a 1-ethoxyethyl group, a 2-methoxyethyl group, a 2-ethoxyethyl group, a 1-methoxy-1-methylethyl group, a 1,2-dimethoxyethyl group, and a 3-methoxypropyl group.

[0042] "(haloC)" in formula (I) 1-6 Alkoxy)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one or two, of the same or different "halo C 1-6 The "C" substituted with an "alkoxy group" 1-6 It means an "alkyl group," and examples thereof include a fluoromethoxymethyl group, a difluoromethoxymethyl group, a trifluoromethoxymethyl group, a 1-(fluoromethoxy)ethyl group, a 1-(difluoromethoxy)ethyl group, a 1-(trifluoromethoxy)ethyl group, a 2-(fluoromethoxy)ethyl group, a 2-(difluoromethoxy)ethyl group, a 2-(trifluoromethoxy)ethyl group, a chloromethoxymethyl group, and a bromomethoxymethyl group.

[0043] "Amino C" in formula (I) 1-6 The term "alkyl group" refers to the above-mentioned "C alkyl group" in which any substitutable position is substituted with one or more, preferably one or two, amino groups. 1-6 It means an "alkyl group," and examples thereof include an aminomethyl group, a 1-aminoethyl group, a 1-aminopropyl group, a 2-aminoethyl group, a 2-aminopropyl group, a 2-amino-1-methylethyl group, a 1-amino-1-methylethyl group, a 1,2-diaminoethyl group, and a 3-aminopropyl group.

[0044] "(mono C 1-6 Alkylamino)C 1-6The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one, of the above-mentioned "mono C 1-6 The "C" substituted with an alkylamino group 1-6 and examples thereof include a methylaminomethyl group, an ethylaminomethyl group, a propylaminomethyl group, an isopropylaminomethyl group, a 1-(methylamino)ethyl group, a 2-(methylamino)ethyl group, and a 2-(isopropylamino)ethyl group.

[0045] In formula (I), "(diC 1-6 Alkylamino)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one of the above-mentioned "diC 1-6 The "C" substituted with an alkylamino group 1-6 It means an "alkyl group," and examples thereof include a dimethylaminomethyl group, a diethylaminomethyl group, a dipropylaminomethyl group, a diisopropylaminomethyl group, a 1-(diisopropylamino)ethyl group, a 2-(diisopropylamino)ethyl group, an (N-ethyl-N-methylamino)methyl group, a 1-(N-ethyl-N-methylamino)ethyl group, and a 2-(N-ethyl-N-methylamino)ethyl group.

[0046] "Carbamoyl C" in formula (I) 1-6 The term "alkyl group" refers to the above-mentioned "C alkyl group" in which any substitutable position is substituted with one or more, preferably one, carbamoyl group. 1-6 It means an "alkyl group," and examples thereof include a carbamoylmethyl group, a 1-carbamoylethyl group, a 1-carbamoylpropyl group, a 2-carbamoylethyl group, a 2-carbamoylpropyl group, a 2-carbamoyl-1-methylethyl group, a 1-carbamoyl-1-methylethyl group, and a 3-carbamoylpropyl group.

[0047] "(mono C 1-6 Alkylcarbamoyl)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one, of the above-mentioned "mono C 1-6 The "C" substituted with an alkylcarbamoyl group 1-6It means an "alkyl group," and examples thereof include a methylcarbamoylmethyl group, an ethylcarbamoylmethyl group, a propylcarbamoylmethyl group, an isopropylcarbamoylmethyl group, a 1-(methylcarbamoyl)ethyl group, a 2-(methylcarbamoyl)ethyl group, a 1-(ethylcarbamoyl)ethyl group, and a 2-(ethylcarbamoyl)ethyl group.

[0048] In formula (I), "(diC 1-6 Alkylcarbamoyl)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one of the above-mentioned "diC 1-6 The "C" substituted with an alkylcarbamoyl group 1-6 It means an "alkyl group," and examples thereof include a dimethylcarbamoylmethyl group, a diethylcarbamoylmethyl group, a dipropylcarbamoylmethyl group, a diisopropylcarbamoylmethyl group, a 1-(dimethylcarbamoyl)ethyl group, a 2-(dimethylcarbamoyl)ethyl group, an (N-ethyl-N-methylcarbamoyl)methyl group, a 1-(N-ethyl-N-methylcarbamoyl)ethyl group, and a 2-(N-ethyl-N-methylcarbamoyl)ethyl group.

[0049] "Sulfamoyl C" in formula (I) 1-6 The term "C alkyl group" refers to the above-mentioned "C alkyl group" in which any substitutable position is substituted with one or more, preferably one, sulfamoyl group. 1-6 It means an "alkyl group," and examples thereof include a sulfamoylmethyl group, a 1-sulfamoylethyl group, a 1-sulfamoylpropyl group, a 2-sulfamoylethyl group, a 2-sulfamoylpropyl group, a 2-sulfamoyl-1-methylethyl group, a 1-sulfamoyl-1-methylethyl group, and a 3-sulfamoylpropyl group.

[0050] "(mono C 1-6 Alkyl sulfamoyl)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one, of the above-mentioned "mono C 1-6 The above "C" substituted with an alkylsulfamoyl group 1-6It means an "alkyl group," and examples thereof include a methylsulfamoylmethyl group, an ethylsulfamoylmethyl group, a propylsulfamoylmethyl group, an isopropylsulfamoylmethyl group, a 1-(methylsulfamoyl)ethyl group, a 2-(methylsulfamoyl)ethyl group, a 1-(ethylsulfamoyl)ethyl group, and a 2-(ethylsulfamoyl)ethyl group.

[0051] In formula (I), "(diC 1-6 Alkyl sulfamoyl)C 1-6 The term "alkyl group" refers to a group in which any substitutable position is one or more, preferably one of the above-mentioned "diC 1-6 The above "C" substituted with an alkylsulfamoyl group 1-6 and examples thereof include a dimethylsulfamoylmethyl group, a diethylsulfamoylmethyl group, a dipropylsulfamoylmethyl group, a diisopropylsulfamoylmethyl group, a 1-(dimethylsulfamoyl)ethyl group, a 2-(dimethylsulfamoyl)ethyl group, an (N-ethyl-N-methylsulfamoyl)methyl group, a 1-(N-ethyl-N-methylsulfamoyl)ethyl group, and a 2-(N-ethyl-N-methylsulfamoyl)ethyl group.

[0052] "C" in formula (I) 1-6 The "alkanediyl group" refers to the group defined above as "C 1-6 It means a divalent group obtained by removing one hydrogen atom from an "alkyl group," and examples thereof include a methylene group, an ethane-1,1-diyl group, an ethane-1,2-diyl group, a propane-1,1-diyl group, a propane-1,2-diyl group, a propane-2,2-diyl group, and a propane-1,3-diyl group.

[0053] "Hydroxy C" in formula (I) 1-6 The term "alkanediyl group" refers to the above-mentioned "C alkanediyl group" in which any substitutable position is substituted with one or more, preferably one or two, hydroxy groups. 1-6It means an "alkanediyl group," and examples thereof include a hydroxymethylene group, a 1-hydroxyethane-1,1-diyl group, a 2-hydroxyethane-1,1-diyl group, a 1-hydroxyethane-1,2-diyl group, a 2-hydroxyethane-1,2-diyl group, a 1,2-dihydroxyethane-1,1-diyl group, and a 1,2-dihydroxyethane-1,2-diyl group.

[0054] "C" in formula (I) 6-10 The term "aryl group" refers to an aromatic hydrocarbon group having 6 to 10 carbon atoms, and examples thereof include a phenyl group and a naphthyl group.

[0055] The "heteroaryl group" in formula (I) means a 5- or 6-membered monocyclic ring containing one or more, preferably 1 to 4, heteroatoms, which may be the same or different, selected from the group consisting of oxygen atoms, nitrogen atoms, and sulfur atoms, or a bicyclic ring in which the monocyclic ring is fused with a benzene ring or a pyridine ring, and examples thereof include a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, a thiazolyl group, an isothiazolyl group, an oxazolyl group, an isoxazolyl group, a triazolyl group, a tetrazolyl group, a 1,2,3-oxadiazolyl group, a 1,2,4-oxadiazolyl group, a 1,3,4-oxadiazolyl group, a 1,2,5-oxadiazolyl group, a 1,2,3-thiadiazolyl group, a 1,2,4- Examples thereof include a thiadiazolyl group, a 1,3,4-thiadiazolyl group, a 1,2,5-thiadiazolyl group, a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, a 1,2,4-triazinyl group, a 1,3,5-triazinyl group, an indolyl group, an isoindolyl group, a benzofuranyl group, a benzothienyl group, a benzimidazolyl group, a benzoxazolyl group, a benzisoxazolyl group, a benzothiazolyl group, a benzisothiazolyl group, an indazolyl group, an imidazopyridyl group, a purinyl group, a quinolyl group, a quinolidinyl group, an isoquinolyl group, a phthalazinyl group, a naphthyridinyl group, a quinoxalinyl group, a quinazolinyl group, a cinnolinyl group, a pteridinyl group, and a pyrido[3,2-b]pyridyl group.

[0056] "C" in formula (I) 3-10The term "cycloalkyl group" means a 3- to 10-membered aliphatic cyclic group, and examples thereof include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and a cyclooctyl group. "C 3-10 The "cycloalkyl group" may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, and examples of such fused ring groups include an indan-1-yl group, an indan-2-yl group, a 1,2,3,4-tetrahydronaphthalen-1-yl group, and a 1,2,3,4-tetrahydronaphthalen-2-yl group. Furthermore, "C 3-10 The "cycloalkyl group" may form a bicyclo or spiro ring group, and examples of such a ring group include a bicyclo[2.2.1]heptyl group, a bicyclo[2.2.2]octyl group, a bicyclo[3.2.1]octyl group, a spiro[2.3]hexyl group, a spiro[3.3]heptyl group, a spiro[2.5]octyl group, and a spiro[3.4]octyl group.

[0057] The "4- to 10-membered heterocyclyl group" in formula (I) refers to an aliphatic cyclic group having 4 to 10 ring-constituting atoms and containing one or more, preferably one to three, heteroatoms which may be the same or different and selected from the group consisting of nitrogen atoms, oxygen atoms, and sulfur atoms. Examples include an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azepanyl group, an oxetanyl group, an oxolanyl group, an oxanyl group, a pyrazolidinyl group, an imidazolidinyl group, an oxazolidinyl group, an isoxazolidinyl group, a thiazolidinyl group, an isothiazolidinyl group, a dioxolanyl group, a dioxanyl group, a morpholinyl group, a piperazinyl group, and a thiomorpholinyl group. The "4- to 10-membered heterocyclyl group" may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, and examples of such fused ring groups include groups represented by the following formula (wherein the wavy line represents the point of attachment): TIFF0007734129000003.tif28170 Furthermore, the "4- to 10-membered heterocyclyl group" may form a bicyclo or spiro ring group, and examples of such ring groups include a 2-azabicyclo[2.2.1]heptyl group, a 1-azabicyclo[2.2.2]octyl group, a 2-azabicyclo[2.2.2]octyl group, a 2-azaspiro[3.3]heptyl group, a 2-azaspiro[3.4]octyl group, and a 2-oxaspiro[3.5]nonyl group.

[0058] The "4-10-membered nitrogen-containing heterocyclyl group" in the general formula (III) is a "4-10-membered heterocyclyl group" that contains one or more, preferably one, nitrogen atom among the atoms constituting the ring and is connected to L of formula (I) via the nitrogen atom. 2 and examples thereof include an azetidinyl group, a pyrrolidinyl group, a piperidinyl group, an azepanyl group, and a 2-azaspiro[3.3]heptyl group.

[0059] "Hydroxy C" in formula (I) 1-6 The term "alkoxy group" refers to the above-mentioned "C alkoxy group" in which any substitutable position is substituted with one or more, preferably one or two, hydroxy groups. 1-6 It means an "alkoxy group," and examples thereof include a 2-hydroxyethoxy group, a 2-hydroxypropoxy group, a 3-hydroxypropoxy group, and a 2-hydroxy-2-methylpropoxy group.

[0060] "C" in formula (I) 1-6 The term "alkylthio group" refers to a group in which the hydrogen atom of a sulfanyl group is substituted with the aforementioned "C 1-6 It means a group substituted with an "alkyl group," and examples thereof include a methylthio group, an ethylthio group, a propylthio group, an isopropylthio group, a butylthio group, a sec-butylthio group, an isobutylthio group, a tert-butylthio group, a pentylthio group, an isopentylthio group, a hexylthio group, and an isohexylthio group.

[0061] The "mono(haloC" in formula (I) 1-6 The term "halo (C alkyl) amino group" refers to a group in which one hydrogen atom of the amino group is substituted with one of the above-mentioned "halo (C alkyl) amino groups."1-6 and examples thereof include a 2-fluoroethylamino group, a 2,2-difluoroethylamino group, a 2,2,2-trifluoroethylamino group, and a 2,2,3,3,3-pentafluoropropylamino group.

[0062] "C" in formula (I) 2-7 The "alkoxycarbonyl group" refers to the "C 1-6 It means a group in which an "alkoxy group" is bonded to a carbonyl group, i.e., an alkoxycarbonyl group having 2 to 7 carbon atoms, and examples thereof include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, an isopropoxycarbonyl group, a butoxycarbonyl group, an isobutoxycarbonyl group, a tert-butoxycarbonyl group, and a pentyloxycarbonyl group.

[0063] In formula (I), "mono(C 2-7 The term "(alkoxycarbonyl)amino group" refers to a group in which one hydrogen atom of the amino group is substituted with the above-mentioned "C 2-7 "alkoxycarbonyl group" means a group substituted with an "alkoxycarbonyl group," and examples thereof include a methoxycarbonylamino group, an ethoxycarbonylamino group, a propoxycarbonylamino group, an isopropoxycarbonylamino group, a butoxycarbonylamino group, an isobutoxycarbonylamino group, a tert-butoxycarbonylamino group, and a pentyloxycarbonylamino group.

[0064] The "oxo group" in formula (I) refers to an oxygen atom (=O) bonded via a double bond. Thus, when an oxo group is bonded to a carbon atom, it forms a carbonyl group together with the carbon atom; when one oxo group is bonded to a sulfur atom, it forms a sulfinyl group together with the sulfur atom; and when two oxo groups are bonded to a sulfur atom, it forms a sulfonyl group together with the sulfur atom. Examples of cyclic groups in which an oxo group is bonded to a carbon atom that constitutes a ring include a 2-oxopyrrolidin-3-yl group, a 2-oxopiperidin-4-yl group, a 6-oxo-1,6-dihydropyridin-2-yl group, a 1-methyl-6-oxo-1,6-dihydropyridin-2-yl group, a 6-oxo-1,6-dihydropyrimidin-2-yl group, and a 1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl group. Examples of the cyclic group in which an oxo group is bonded to a sulfur atom constituting the ring include a 1,1-dioxoisothiazolidin-5-yl group and a 1,1-dioxothiomorpholin-4-yl group.

[0065] "Any substitutable position" means a substitutable hydrogen atom on a carbon, nitrogen, oxygen, and / or sulfur atom where substitution of the hydrogen atom is chemically permissible and results in a stable compound.

[0066] Next, each group constituting formula (I) will be explained in detail.

[0067] R in formula (I) 1 is a hydrogen atom, a halogen atom or C 1-6 It represents an alkyl group, preferably a hydrogen atom. R 1 The halogen atom is preferably a fluorine atom or a chlorine atom. R 1 C 1-6 The alkyl group is preferably a methyl group or an ethyl group.

[0068] R in formula (I) 2 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, a carbamoyl group, C 1-6 Alkyl group, halo C1-6 Alkyl group, hydroxy C 1-6 Alkyl group or C 1-6 represents an alkoxy group, and is preferably a hydrogen atom, a halogen atom, or C 1-6 It is an alkyl group. R 2 The halogen atom is preferably a fluorine atom or a chlorine atom. R 2 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 2 Haro C 1-6 The alkyl group is preferably a trifluoromethyl group or a 2,2,2-trifluoroethyl group. R 2 Hydroxy C 1-6 The alkyl group is preferably a hydroxymethyl group or a 1-hydroxyethyl group. R 2 C 1-6 The alkoxy group is preferably a methoxy group or an ethoxy group.

[0069] R in formula (I) 3 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl group, C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl)C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkylsulfonylamino group, mono C1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, C 3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, or a halocyclic amino group, and is preferably a hydrogen atom, a halogen atom, or C 1-6 It is an alkyl group. R 3 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 3 C 2-6 The alkenyl group is preferably a vinyl group or an allyl group. R 3 Haro C 1-6 The alkyl group is preferably a trifluoromethyl group or a 2,2,2-trifluoroethyl group. R 3 Hydroxy C 1-6 The alkyl group is preferably a hydroxymethyl group or a 1-hydroxyethyl group. R 3 C 2-7 The alkanoyl group is preferably an acetyl group or a propanoyl group. R 3 C 1-6 The alkylsulfonyl group is preferably a methylsulfonyl group or an ethylsulfonyl group. R 3 C 1-6 The alkoxy group is preferably a methoxy group or an ethoxy group. R 3 Haro C 1-6 The alkoxy group is preferably a difluoromethoxy group or a trifluoromethoxy group. R 3 C 1-6 The alkylsulfonyloxy group is preferably a methylsulfonyloxy group or an ethylsulfonyloxy group. R 3 Haro C 1-6The alkylsulfonyloxy group is preferably a trifluoromethylsulfonyloxy group or a 2,2,2-trifluoroethylsulfonyloxy group. R 3 Mono C 1-6 The alkylamino group is preferably a methylamino group or an ethylamino group. R 3 The C 1-6 The alkylamino group is preferably a dimethylamino group or an N-ethyl-N-methylamino group. R 3 Mono C 2-7 The alkanoylamino group is preferably an acetylamino group or a propanoylamino group. R 3 (C 2-7 Alkanoyl)C 1-6 The alkylamino group is preferably an N-acetyl-N-methylamino group or an N-acetyl-N-ethylamino group. R 3 The C 2-7 The alkanoylamino group is preferably a diacetylamino group or a dipropanoylamino group. R 3 Mono C 1-6 The alkylsulfonylamino group is preferably a methylsulfonylamino group or an ethylsulfonylamino group. R 3 Mono C 1-6 The alkylcarbamoyl group is preferably a methylcarbamoyl group or an ethylcarbamoyl group. R 3 The C 1-6 The alkylcarbamoyl group is preferably a dimethylcarbamoyl group or an N-ethyl-N-methylcarbamoyl group. R 3 Mono C 1-6 The alkylsulfamoyl group is preferably a methylsulfamoyl group or an ethylsulfamoyl group. R 3 The C 1-6 The alkylsulfamoyl group is preferably a dimethylsulfamoyl group or an N-ethyl-N-methylsulfamoyl group. R3 C 3-6 The cycloalkyl group is preferably a cyclopropyl group or a cyclobutyl group. R 3 The cyclic ether group is preferably an oxetanyl group or an oxolanyl group. R 3 The cyclic amino group is preferably an azetidin-1-yl group or a pyrrolidin-1-yl group. R 3 The halocyclic amino group is preferably a 3,3-difluoroazetidin-1-yl group or a 3,3-difluoropyrrolidin-1-yl group.

[0070] R in formula (I) 4 represents a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, mono C 1-6 Alkylamino group or diC 1-6 represents an alkylamino group, and is preferably a hydrogen atom, a halogen atom, or C 1-6 It is an alkyl group. R 4 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 4 C 2-6 The alkenyl group is preferably a vinyl group or an allyl group. R 4 Haro C 1-6 The alkyl group is preferably a trifluoromethyl group or a 2,2,2-trifluoroethyl group. R 4 Hydroxy C 1-6 The alkyl group is preferably a hydroxymethyl group or a 1-hydroxyethyl group. R 4 C 1-6 The alkoxy group is preferably a methoxy group or an ethoxy group. R 4 Haro C 1-6 The alkoxy group is preferably a difluoromethoxy group or a trifluoromethoxy group. R 4 Mono C 1-6 The alkylamino group is preferably a methylamino group or an ethylamino group. R 4 The C 1-6 The alkylamino group is preferably a dimethylamino group or an N-ethyl-N-methylamino group.

[0071] R in formula (I) 5 is a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, C 1-6 Alkyl group, halo C 1-6 Alkyl or hydroxy C 1-6 It represents an alkyl group, and is preferably a hydrogen atom or a fluorine atom. R 5 The halogen atom is preferably a fluorine atom or a chlorine atom. R 5 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 5 Haro C 1-6 The alkyl group is preferably a trifluoromethyl group or a 2,2,2-trifluoroethyl group. R 5 Hydroxy C 1-6 The alkyl group is preferably a hydroxymethyl group or a 1-hydroxyethyl group.

[0072] W in formula (I) is an oxygen atom, a sulfur atom, or a group represented by the general formula: -N(R 6 )-(R 6 is a hydrogen atom or C 1-6 represents an alkyl group), and is preferably an oxygen atom or a group represented by the general formula: -N(R 6 )-(wherein, R 6 has the same meaning as above), and more preferably an oxygen atom or —NH—. R 6 C 1-6The alkyl group is preferably a methyl group or an ethyl group.

[0073] X in formula (I) is C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group, (haloC 1-6 Alkoxy)C 1-6 Alkyl group, amino C 1-6 Alkyl group, (mono C 1-6 Alkylamino)C 1-6 Alkyl group, (diC 1-6 Alkylamino)C 1-6 Alkyl group, carbamoyl C 1-6 Alkyl group, (mono C 1-6 Alkylcarbamoyl)C 1-6 Alkyl group, (diC 1-6 Alkylcarbamoyl)C 1-6 Alkyl group, sulfamoyl C 1-6 Alkyl group, (mono C 1-6 Alkyl sulfamoyl)C 1-6 Alkyl group, (diC 1-6 Alkyl sulfamoyl)C 1-6 an alkyl group, or General formula (II): TIFF0007734129000004.tif2561(in the formula, The wavy line represents the point of attachment to the nitrogen atom; L 1 is a single bond, C 1-6 Alkanediyl group or hydroxy C 1-6 represents an alkanediyl group; Ring Y is C 6-10 Aryl groups, heteroaryl groups, C 3-10 Cycloalkyl group (C 3-10a cycloalkyl group which may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may be fused with a bicyclo ring group or a spiro ring group, or a 4- to 10-membered heterocyclyl group which may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may be fused with a bicyclo ring group or a spiro ring group; R 7 are each independently a halogen atom, a cyano group, a hydroxy group, a sulfanyl group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, a formyl group, an imino group, an azido group, a hydrazino group, a nitro group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group, C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, hydroxy C 1-6 Alkoxy group, C 1-6 Alkylthio group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, mono(haloC 1-6 alkyl)amino group, C 2-7 Alkoxycarbonyl group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl)C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkyl sulfonyl amino group, mono(C 2-7 Alkoxycarbonyl)amino group, C3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, a halocyclic amino group, or an oxo group; L 2 is a single bond, C 1-6 Alkanediyl group, hydroxy C 1-6 represents an alkanediyl group, a carbonyl group, or a sulfonyl group; Ring Z represents a phenyl group, a heteroaryl group, or a 4- to 10-membered heterocyclyl group (the 4- to 10-membered heterocyclyl group may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may form a bicyclo ring group or a spiro ring group); R 8 are each independently a halogen atom, a cyano group, a hydroxy group, a sulfanyl group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, or C 1-6 Alkyl group, C 2-6 Alkenyl group, haloC 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group, C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, haloC 1-6 Alkoxy group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, C 2-7 Alkoxycarbonyl group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, mono C 2-7 Alkanoylamino group, mono C 1-6 Alkyl sulfonyl amino group, mono(C 2-7 Alkoxycarbonyl)amino group, C 3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, a halocyclic amino group, or an oxo group; m represents 0, 1, 2 or 3; n represents 0, 1, or 2; and p is a group represented by the formula:

[0074] X's C 1-6 The alkyl group is preferably a butyl group or a hexyl group. X's C 2-6 The alkenyl group is preferably a vinyl group or an allyl group. X's Halo C 1-6 The alkyl group is preferably a 2,2,2-trifluoroethyl group or a 2,2,3,3,3-pentafluoropropyl group. X hydroxy C 1-6 The alkyl group is preferably a 3-hydroxypropyl group or a 2-hydroxypropyl group. X's (C 1-6 Alkoxy)C 1-6 The alkyl group is preferably a 3-methoxypropyl group or a 2-ethoxyethyl group. X's (Halo C 1-6 Alkoxy)C 1-6 The alkyl group is preferably a 2-(difluoromethoxy)ethyl group or a 2-(trifluoromethoxy)ethyl group. X Amino C 1-6 The alkyl group is preferably a 2-aminoethyl group or a 2-aminopropyl group. X's (mono C 1-6 Alkylamino)C 1-6 The alkyl group is preferably a 2-(methylamino)ethyl group or a 2-(isopropylamino)ethyl group. X's (C 1-6 Alkylamino)C 1-6 The alkyl group is preferably a 2-(diisopropylamino)ethyl group or a 2-(N-ethyl-N-methylamino)ethyl group. X Carbamoyl C 1-6 The alkyl group is preferably a 2-carbamoylethyl group or a 2-carbamoylpropyl group. X's (mono C 1-6 Alkylcarbamoyl)C 1-6The alkyl group is preferably a 2-(methylcarbamoyl)ethyl group or a 2-(ethylcarbamoyl)ethyl group. X's (C 1-6 Alkylcarbamoyl)C 1-6 The alkyl group is preferably a 2-(dimethylcarbamoyl)ethyl group or a 2-(N-ethyl-N-methylcarbamoyl)ethyl group. X sulfamoyl C 1-6 The alkyl group is preferably a 2-sulfamoylethyl group or a 2-sulfamoylpropyl group. X's (mono C 1-6 Alkyl sulfamoyl)C 1-6 The alkyl group is preferably a 2-(methylsulfamoyl)ethyl group or a 2-(ethylsulfamoyl)ethyl group. X's (C 1-6 Alkyl sulfamoyl)C 1-6 The alkyl group is preferably a 2-(dimethylsulfamoyl)ethyl group or a 2-(N-ethyl-N-methylsulfamoyl)ethyl group.

[0075] L 1 C 1-6 The alkanediyl group is preferably a methylene group or a propane-1,3-diyl group. L 1 Hydroxy C 1-6 The alkanediyl group is preferably a 2-hydroxyethane-1,1-diyl group or a 2-hydroxyethane-1,2-diyl group. L 1 is preferably a single bond or a methylene group.

[0076] Ring Y C 6-10 The aryl group is preferably a phenyl group or a naphthyl group. The heteroaryl group of ring Y is preferably a pyrazolyl group or a pyridyl group. Ring Y C 3-10 The cycloalkyl group is preferably a cyclohexyl group, an indan-1-yl group, or a spiro[3.3]heptyl group. The 4- to 10-membered heterocyclyl group for ring Y is preferably a 4- to 10-membered nitrogen-containing heterocyclyl group or a fused heterocyclyl group formed by condensing a 4- to 10-membered heterocyclyl group with a benzene ring or a heteroaryl ring. Ring Y is preferably represented by the general formula (III): TIFF0007734129000005.tif2025(in the formula, The wavy line is L 1 represents the point of attachment to *L 2 represents the point of attachment to R 7 and m are as defined above, Ring A is a 4-10 membered nitrogen-containing heterocyclyl group; Ring Y is more preferably of the general formula: TIFF0007734129000006.tif15170 (in the formula, The wavy line is L 1 represents the point of attachment to *L 2 represents the point of attachment to R 7 and m has the same meaning as above). Preferred examples of ring Y include fused heterocyclyl groups formed by condensing a 4- to 10-membered heterocyclyl group with a benzene ring or a heteroaryl ring; More preferred examples of ring Y include rings represented by the general formula: TIFF0007734129000007.tif51170 (in the formula, The wavy line is L 1 represents the point of attachment to R 7 and m has the same meaning as defined above).

[0077] R 7 The halogen atom is preferably a fluorine atom or a chlorine atom. R 7 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 7 C 2-6 The alkenyl group is preferably a vinyl group or an allyl group. R 7 Haro C 1-6 The alkyl group is preferably a trifluoromethyl group or a 2,2,2-trifluoroethyl group. R 7 Hydroxy C 1-6 The alkyl group is preferably a hydroxymethyl group or a 1-hydroxy-1-methylethyl group. R 7 (C 1-6 Alkoxy)C 1-6 The alkyl group is preferably a 2-methoxyethyl group or a 2-ethoxyethyl group. R 7 C 2-7 The alkanoyl group is preferably an acetyl group or a propanoyl group. R 7 C 1-6 The alkylsulfonyl group is preferably a methylsulfonyl group or an ethylsulfonyl group. R 7 C 1-6 The alkoxy group is preferably a methoxy group or an ethoxy group. R 7 Haro C 1-6 The alkoxy group is preferably a difluoromethoxy group or a trifluoromethoxy group. R 7 Hydroxy C 1-6 The alkoxy group is preferably a 2-hydroxyethoxy group or a 2-hydroxy-2-methylpropoxy group. R 7 C 1-6 The alkylthio group is preferably a methylthio group or an ethylthio group. R 7 Mono C 1-6 The alkylamino group is preferably a methylamino group or an ethylamino group. R 7 The C 1-6 The alkylamino group is preferably a dimethylamino group or an N-ethyl-N-methylamino group. R 7 Nomono (Haro C 1-6The (alkyl)amino group is preferably a 2,2-difluoroethylamino group or a 2,2,2-trifluoroethylamino group. R 7 C 2-7 The alkoxycarbonyl group is preferably a methoxycarbonyl group or an ethoxycarbonyl group. R 7 Mono C 1-6 The alkylcarbamoyl group is preferably a methylcarbamoyl group or an ethylcarbamoyl group. R 7 The C 1-6 The alkylcarbamoyl group is preferably a dimethylcarbamoyl group or an N-ethyl-N-methylcarbamoyl group. R 7 C 1-6 The alkylsulfonyloxy group is preferably a methylsulfonyloxy group or an ethylsulfonyloxy group. R 7 Haro C 1-6 The alkylsulfonyloxy group is preferably a trifluoromethylsulfonyloxy group or a 2,2,2-trifluoroethylsulfonyloxy group. R 7 Mono C 1-6 The alkylsulfamoyl group is preferably a methylsulfamoyl group or an ethylsulfamoyl group. R 7 The C 1-6 The alkylsulfamoyl group is preferably a dimethylsulfamoyl group or an N-ethyl-N-methylsulfamoyl group. R 7 Mono C 2-7 The alkanoylamino group is preferably an acetylamino group or a propanoylamino group. R 7 (C 2-7 Alkanoyl)C 1-6 The alkylamino group is preferably an N-acetyl-N-methylamino group or an N-acetyl-N-ethylamino group. R 7 The C 2-7 The alkanoylamino group is preferably a diacetylamino group or a dipropanoylamino group. R 7 Mono C 1-6 The alkylsulfonylamino group is preferably a methylsulfonylamino group or an ethylsulfonylamino group. R 7 Mono (C 2-7 The alkoxycarbonylamino group is preferably a methoxycarbonylamino group or a tert-butoxycarbonylamino group. R 7 C 3-6 The cycloalkyl group is preferably a cyclopropyl group or a cyclobutyl group. R 7 The cyclic ether group is preferably an oxetanyl group or an oxolanyl group. R 7 The cyclic amino group is preferably an azetidin-1-yl group or a pyrrolidin-1-yl group. R 7 The halocyclic amino group is preferably a 3,3-difluoroazetidin-1-yl group or a 3,3-difluoropyrrolidin-1-yl group. R 7 The cyclic group in which the oxo group is bonded to a carbon atom constituting the ring is preferably a 2-oxopyrrolidin-3-yl group or a 2-oxopiperidin-4-yl group. R 7 The cyclic group in which the oxo group is bonded to a sulfur atom constituting the ring is preferably a 1,1-dioxoisothiazolidin-5-yl group or a 1,1-dioxothiomorpholin-4-yl group.

[0078] L 2 C 1-6 The alkanediyl group is preferably a methylene group or an ethane-1,2-diyl group. L 2 Hydroxy C 1-6 The alkanediyl group is preferably a hydroxymethylene group or a 1-hydroxyethane-1,1-diyl group.

[0079] The heteroaryl group of ring Z is preferably a tetrazolyl group or a pyrimidinyl group. The 4- to 10-membered heterocyclyl group for ring Z is preferably a pyrrolidinyl group or an isothiazolidinyl group. Ring Z is preferably a phenyl group or a heteroaryl group (preferably a 5- or 6-membered nitrogen-containing heteroaryl group), more preferably a ring represented by the general formula: TIFF0007734129000008.tif46146 (in the formula, The wavy line is L 2 represents the point of attachment to R 8 and n is as defined above, R 9 is C 1-6 Alkyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group or C 3-6 is a cycloalkyl group.

[0080] R 8 The halogen atom is preferably a fluorine atom or a chlorine atom. R 8 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 8 C 2-6 The alkenyl group is preferably a vinyl group or an allyl group. R 8 Haro C 1-6 The alkyl group is preferably a trifluoromethyl group or a 2,2,2-trifluoroethyl group. R 8 Hydroxy C 1-6 The alkyl group is preferably a hydroxymethyl group or a 1-hydroxy-1-methylethyl group. R 8 (C 1-6 Alkoxy)C 1-6 The alkyl group is preferably a methoxymethyl group or an ethoxymethyl group. R 8 C 2-7 The alkanoyl group is preferably an acetyl group or a propanoyl group. R8 C 1-6 The alkylsulfonyl group is preferably a methylsulfonyl group or an ethylsulfonyl group. R 8 C 1-6 The alkoxy group is preferably a methoxy group or an ethoxy group. R 8 Haro C 1-6 The alkoxy group is preferably a difluoromethoxy group or a trifluoromethoxy group. R 8 Mono C 1-6 The alkylamino group is preferably a methylamino group or an ethylamino group. R 8 The C 1-6 The alkylamino group is preferably a dimethylamino group or an N-ethyl-N-methylamino group. R 8 C 2-7 The alkoxycarbonyl group is preferably a methoxycarbonyl group or an ethoxycarbonyl group. R 8 Mono C 1-6 The alkylcarbamoyl group is preferably a methylcarbamoyl group or an ethylcarbamoyl group. R 8 The C 1-6 The alkylcarbamoyl group is preferably a dimethylcarbamoyl group or an N-ethyl-N-methylcarbamoyl group. R 8 C 1-6 The alkylsulfonyloxy group is preferably a methylsulfonyloxy group or an ethylsulfonyloxy group. R 8 Haro C 1-6 The alkylsulfonyloxy group is preferably a trifluoromethylsulfonyloxy group or a 2,2,2-trifluoroethylsulfonyloxy group. R 8 Mono C 1-6 The alkylsulfamoyl group is preferably a methylsulfamoyl group or an ethylsulfamoyl group. R 8 The C 1-6The alkylsulfamoyl group is preferably a dimethylsulfamoyl group or an N-ethyl-N-methylsulfamoyl group. R 8 Mono C 2-7 The alkanoylamino group is preferably an acetylamino group or a propanoylamino group. R 8 (C 2-7 Alkanoyl)C 1-6 The alkylamino group is preferably an N-acetyl-N-methylamino group or an N-acetyl-N-ethylamino group. R 8 The C 2-7 The alkanoylamino group is preferably a diacetylamino group or a dipropanoylamino group. R 8 Mono C 1-6 The alkylsulfonylamino group is preferably a methylsulfonylamino group or an ethylsulfonylamino group. R 8 Mono (C 2-7 The alkoxycarbonylamino group is preferably a methoxycarbonylamino group or a tert-butoxycarbonylamino group. R 8 C 3-6 The cycloalkyl group is preferably a cyclopropyl group or a cyclobutyl group. R 8 The cyclic ether group is preferably an oxetanyl group or an oxolanyl group. R 8 The cyclic amino group is preferably an azetidin-1-yl group or a pyrrolidin-1-yl group. R 8 The halocyclic amino group is preferably a 3,3-difluoroazetidin-1-yl group or a 3,3-difluoropyrrolidin-1-yl group.

[0081] When p is 1, m is preferably 0, and when p is 0, m is preferably 1 or 2. n is preferably 0 or 1.

[0082] In one embodiment of the present invention, X is preferably a group represented by general formula (II).

[0083] In one embodiment of the present invention, the group represented by general formula (II) is preferably a group in which p is 1 and ring Y is represented by general formula (III): TIFF0007734129000009.tif2025(in the formula, The wavy line is L 1 represents the point of attachment to *L 2 represents the point of attachment to R 7 and m are as defined above, Ring A is a 4-10 membered nitrogen-containing heterocyclyl group, More preferably, m is 0 or L 2 is a single bond.

[0084] In one embodiment of the present invention, the group represented by general formula (II) is preferably one in which p is 1 and ring Y is represented by the general formula: TIFF0007734129000010.tif15170 (in the formula, The wavy line is L 1 represents the point of attachment to *L 2 represents the point of attachment to R 7 and m has the same meaning as above), and more preferably, m is 0 or L 2 is a single bond.

[0085] In one embodiment of the present invention, the group represented by general formula (II) is preferably one in which p is 1 and ring Z is a phenyl group or a heteroaryl group.

[0086] In one embodiment of the present invention, the group represented by general formula (II) is preferably one in which p is 1 and ring Z is a phenyl group or a 5- or 6-membered nitrogen-containing heteroaryl group.

[0087] In one embodiment of the present invention, the group represented by general formula (II) is preferably a group in which p is 1 and ring Z is represented by the general formula: TIFF0007734129000011.tif46146 (in the formula, The wavy line is L 2 represents the point of attachment to R 8 and n is as defined above, R 9 is C 1-6 Alkyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 Alkyl groups, (C 1-6 Alkoxy)C 1-6 Alkyl group or C 3-6 It is represented by R 9 is R 8 is bonded via a nitrogen atom constituting ring Z, 8 are the options. R 9 C 1-6 The alkyl group is preferably a methyl group or an ethyl group. R 9 Haro C 1-6 The alkyl group is preferably a 2,2,2-trifluoroethyl group or a 2,2,3,3,3-pentafluoropropyl group. R 9 Hydroxy C 1-6 The alkyl group is preferably a 2-hydroxyethyl group or a 3-hydroxypropyl group. R 9 (C 1-6 Alkoxy)C 1-6 The alkyl group is preferably a 2-methoxyethyl group or a 2-ethoxyethyl group. R 9 C 3-6 The cycloalkyl group is preferably a cyclopropyl group or a cyclobutyl group.

[0088] In one embodiment of the present invention, the group represented by general formula (II) is preferably such that p is 0 and ring Y is C 3-10 Cycloalkyl group (C 3-10a cycloalkyl group which may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or which may be fused with a bicyclo ring group or a spiro ring group, or a 4- to 10-membered heterocyclyl group which may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or which may be fused with a bicyclo ring group or a spiro ring group; It is what it is.

[0089] In one embodiment of the present invention, the group represented by general formula (II) is preferably a group in which p is 0 and ring Y is C 3-10 Cycloalkyl group (C 3-10 The cycloalkyl group may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may form a bicyclic or spirocyclic group.

[0090] In one embodiment of the present invention, the group represented by general formula (II) is preferably one in which p is 0 and ring Y is a fused heterocyclyl group formed by condensing a 4- to 10-membered heterocyclyl group with a benzene ring or a heteroaryl ring.

[0091] In one embodiment of the present invention, the group represented by general formula (II) is preferably one in which p is 0 and ring Y is represented by the general formula: TIFF0007734129000012.tif51170 (in the formula, The wavy line is L 1 represents the point of attachment to R 7 and m has the same meaning as above).

[0092] In one aspect of the present invention, the group represented by general formula (II) is preferably L 1 is a methylene group, p is 0, and ring Y is of the general formula: TIFF0007734129000013.tif51170 (in the formula, The wavy line is L 1 represents the point of attachment to R 7and m has the same meaning as above).

[0093] In one embodiment of the present invention, the group represented by general formula (II) is preferably one in which p is 0 and ring Y is represented by the general formula: TIFF0007734129000014.tif30124 (in the formula, The wavy line is L 1 represents the point of attachment to R 7 and m has the same meaning as above).

[0094] Specific examples of the compound of the present invention include those described in the Examples, and among them, the following compounds (1) to (49) are preferred. (1) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (2) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(thieno[3,2-c]pyridin-4-yl)benzamide; (3) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide; (4) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-tetrazol-5-yl)piperidin-4-yl]benzamide; (5) 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(2,2,2-trifluoroethyl)amino]cyclohexyl}benzamide; (6) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (7) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (8) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (9) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-methylfuro[3,2-c]pyridin-4-yl)benzamide; (10) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)piperidin-4-yl]benzamide; (11) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]benzamide; (12) (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)pyrrolidin-3-yl]benzamide; (13) (S)-4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide; (14) N-(chroman-3-ylmethyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide; (15) 4-(furo[3,2-c]pyridin-4-yl)-N-(1-propionylpiperidin-4-yl)benzamide; (16) N-[1-(cyclopropanecarbonyl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide; (17) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(oxetan-3-yl)piperidin-4-yl]benzamide; (18) N-[1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide; (19) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]benzamide; (20) 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxycyclohexyl)benzamide; (21) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(1-hydroxycyclopropyl)cyclohexyl]benzamide; (22) 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide; (23) 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxy-4-methylcyclohexyl)benzamide; (24) 4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)benzamide; (25) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(methoxy-d3)cyclohexyl]benzamide; (26) 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-isopropoxycyclohexyl)benzamide; (27) N-{trans-4-[(2,2-difluoroethyl)amino]cyclohexyl}-4-(furo[3,2-c]pyridin-4-yl)benzamide; (28) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(oxetan-3-ylamino)cyclohexyl]benzamide; (29) 4-[6-(hydroxymethyl)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (30) 4-[6-(hydroxymethyl-d2)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (31) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide; (32) N-[trans-4-(1-hydroxycyclopropyl)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (33) N-[1-(pyrimidin-2-yl)piperidin-4-yl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (34) N-( trans -4-hydroxycyclohexyl)-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (35) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(6-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (36) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (37) 3-fluoro-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (38) N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (39) N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (40) N-(trans-4-hydroxy-4-methylcyclohexyl)-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (41) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)benzamide; (42) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxy-4-methylcyclohexyl)benzamide; (43) 3-Fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide; (44) 4-(furo[3,2-c]pyridin-4-yl)-N-[cis-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide; (45) 4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)benzamide; (46) N-(4-cyanobicyclo[2.2.2]octan-1-yl)-4-(furo[3,2-c]pyridin-4-yl)benzamide; (47) 4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]bicyclo[2.2.2]octane-1-carboxamide; (48) 4-(furo[3,2-c]pyridin-4-yl)-N-{cis-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide; and (49) 4-(furo[3,2-c]pyridin-4-yl)-N-[cis-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0095] The compounds of formula (I) may have asymmetric centers, chiral axes, and chiral planes. Compounds of formula (I) may occur as racemates, as racemic mixtures and as individual diastereomers. The compounds of formula (I) include all possible isomers, including optical isomers, and mixtures thereof. Compounds of formula (I) may exist as tautomers, and both tautomeric forms are encompassed by the present invention, even if only one tautomeric structure is depicted herein.

[0096] The compound of formula (I) includes an isotope in which one or more atoms in the molecule are replaced with their isotopes. As used herein, an isotope refers to an atom having the same atomic number but a different mass number. Therefore, as used herein, "substituted with an isotope" refers to a substitution with an atom having the same atomic number but a different mass number from that normally occurring in nature. For example, the hydrogen atoms constituting the compound of formula (I) are 2 H(D) or 3 Similarly, the carbon atoms constituting formula (I) may be substituted with H(T). 11 C. 13 C or 14 It may be substituted with C. 2 Isotopologues substituted with stable isotopes such as H(D) are useful because they may offer therapeutic advantages due to their greater metabolic stability. 3 H(T) and 14 Isotopologues substituted with radioactive isotopes, such as C, are useful in drug and / or substrate tissue distribution studies, and can be prepared by methods disclosed herein or analogous thereto using appropriate reagents containing the corresponding isotope.

[0097] The "pharmaceutically acceptable salt" of the compound of formula (I) is not particularly limited as long as it is pharmaceutically acceptable. For example, when the compound of formula (I) has a carboxyl group, a hydroxyl group, or an acidic heteroaryl group (such as a tetrazolyl group), it may be a base addition salt at the carboxyl group, hydroxyl group, or acidic heteroaryl group; when the compound of formula (I) has an amino group or a basic heteroaryl group, it may be an acid addition salt at the amino group or basic heteroaryl group.

[0098] Examples of base addition salts include alkali metal salts (e.g., sodium salts and potassium salts); alkaline earth metal salts (e.g., calcium salts and magnesium salts); ammonium salts; and organic amine salts (e.g., trimethylamine salts, triethylamine salts, dicyclohexylamine salts, ethanolamine salts, diethanolamine salts, triethanolamine salts, procaine salts, and N,N'-dibenzylethylenediamine salts).

[0099] Examples of acid addition salts include inorganic acid salts (e.g., hydrochlorides, sulfates, nitrates, phosphates, and perchlorates); organic acid salts (e.g., maleates, fumarates, tartrates, citrates, ascorbates, and trifluoroacetates); and sulfonates (e.g., methanesulfonates, isethionates, benzenesulfonates, and p-toluenesulfonates).

[0100] The "pharmaceutically acceptable salt" can be prepared according to a method used in the field of organic synthesis, for example, by neutralizing a solution of the free form of the compound of formula (I) with an alkaline or acidic solution.

[0101] "Pharmaceutically acceptable salts" also include solvates with pharmaceutically acceptable solvents such as water or ethanol.

[0102] Next, the methods for producing the compounds of the present invention will be specifically explained, but the methods are not limited to these. The reaction order can be changed appropriately, and the compounds may be produced starting from any step that seems rational. A step of substituent conversion (conversion or further modification of a substituent) may be inserted between each step. If a reactive functional group is present, it may be protected or deprotected. Protective groups and methods for protection and deprotection can be those used in the field of organic synthesis. For example, methods described in the literature [see Protective Groups in Organic Synthesis, 3rd Edition, T.W. Greene, John Wiley & Sons (1999)] or methods based thereon can be used as appropriate. Protection and deprotection can be performed any number of times at any step, as necessary.

[0103] Unless otherwise specified, in the following preparation methods, for convenience, the free compounds are used, but the preparations can also be carried out using salts of the free compounds. To accelerate the progress of the reaction, a reagent other than the exemplified reagents may be used as appropriate. For heating in each reaction, microwave irradiation may be used as necessary. The starting compounds for which the preparation method has not been described are commercially available or can be easily prepared by combining known synthetic reactions. The compounds obtained in each step may be isolated and purified by conventional means (crystallization, recrystallization, column chromatography, preparative HPLC, etc.), or may be used for the next step without isolation or purification.

[0104] Production Method 1: Production Method of Compounds of Formula (I) (Part 1)

[0105] TIFF0007734129000015.tif47146

[0106] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , W and X are as defined above; M is a boronic acid, a boronic acid ester, a trifluoroborate salt, a cyclic triol borate salt, or the like; LG represents a leaving group such as a halogen atom or a trifluoromethanesulfonyloxy group.

[0107] Step 1: A compound of formula (1) (hereinafter also referred to as "compound (1)") and a compound of formula (2) (hereinafter also referred to as "compound (2)") are reacted in the presence of a condensing agent to obtain a compound of formula (3) (hereinafter also referred to as "compound (3)"). Examples of the compound (1) include the following boronic acid (1a), boronic acid ester (1b), trifluoroborate (1c), and cyclic triol borate (1d).

[0108] TIFF0007734129000016.tif28132

[0109] Compound (2) can be a commercially available product, but it may also be produced by a known method, a method described in the Examples, or a method similar thereto, in appropriate combination as required. Examples of condensing agents include N,N'-dicyclohexylcarbodiimide (DCC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC), N,N'-carbonyldiimidazole (CDI), diphenylphosphoryl azide (DPPA), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU), and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU). A base may be used as necessary in Step 1. Examples of the base include N,N-diisopropylethylamine, triethylamine, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, tripotassium phosphate, potassium fluoride, cesium fluoride, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, etc., and N,N-diisopropylethylamine and triethylamine are particularly preferred. The reaction solvent is not particularly limited as long as it does not interfere with the reaction, and examples thereof include N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, dimethyl sulfoxide, acetonitrile, ethyl acetate, toluene, methanol, ethanol, and water. N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dichloromethane, and chloroform are particularly preferred. The amount of compound (2) used is usually 1 to 3 moles, preferably 1 to 2 moles, per mole of compound (1). The amount of the base used is usually 1 to 10 moles, preferably 1 to 3 moles, per mole of Compound (1). The reaction temperature is usually 0 to 100°C, preferably 0 to 60°C. The reaction time is usually 10 minutes to 24 hours, preferably 30 minutes to 5 hours.

[0110] Step 2: Compound (3) and a compound of formula (4) (hereinafter also referred to as "compound (4)") are subjected to a coupling reaction in the presence of a palladium catalyst and a base to obtain a compound of formula (I). Compound (4) can be a commercially available product, but may also be prepared by a known method, a method described in the Examples, or a method similar thereto, suitably combining these methods as necessary. Examples of palladium catalysts include tetrakis(triphenylphosphine)palladium(0), palladium(II) acetate, tris(dibenzylideneacetone)dipalladium(0), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II). In step 2, a phosphine ligand may be used, if necessary. Examples of the phosphine ligand include triphenylphosphine, tris(2-methylphenyl)phosphine, tri(2-furyl)phosphine, tri-tert-butylphosphine, (4-dimethylaminophenyl)di-tert-butylphosphine (Amphos), 2-[di(tert-butyl)phosphino]-1,1'-biphenyl (JohnPhos), 2-[di(tert-butyl)phosphino]-2'-N,N-dimethylamino-1,1'-biphenyl (tBuDavePhos), 2-(diphenylphosphine)-2'-N,N-dimethylamino-1,1'-biphenyl (tBuDavePhos), and the like. Examples include 2-(dicyclohexylphosphino)-1,1'-biphenyl (CyJohnPhos), 2-(dicyclohexylphosphino)-2'-N,N-dimethylamino-1,1'-biphenyl (DavePhos), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). Examples of the base include sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, tripotassium phosphate, potassium fluoride, cesium fluoride, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, N,N-diisopropylethylamine, triethylamine, and the like. The reaction solvent is not particularly limited as long as it does not interfere with the reaction, and examples thereof include tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, toluene, methanol, ethanol, acetonitrile, water, and the like. The reaction solvent may be a single solvent or a mixed solvent of two or more solvents. Examples of mixed solvents include a combination of methanol and water, a combination of ethanol and water, a combination of toluene and water, and a combination of 1,4-dioxane and water. The amount of compound (3) used is usually 1 to 3 moles, preferably 1 to 2 moles, per mole of compound (4). The amount of the palladium catalyst used is usually 0.01 to 0.5 mol, preferably 0.03 to 0.2 mol, per 1 mol of compound (4). The amount of the base used is usually 1 to 10 moles, preferably 1 to 3 moles, per mole of compound (4). The reaction temperature is usually 20 to 160°C, preferably 20 to 120°C. The reaction time is usually 10 minutes to 24 hours, preferably 30 minutes to 5 hours.

[0111] Production Method 2: Production Method of Compound of Formula (I) (Part 2)

[0112] TIFF0007734129000017.tif47148

[0113] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , W and X are as defined above; M is a boronic acid, a boronic acid ester, a trifluoroborate salt, a cyclic triol borate salt, or the like; LG is a leaving group such as a halogen atom or a trifluoromethanesulfonyloxy group; R a is C 1-6 represents an alkyl group.

[0114] Step 3: A compound of formula (5) (hereinafter also referred to as "compound (5)") and compound (4) are subjected to a coupling reaction in the presence of a palladium catalyst and a base to obtain a compound of formula (6) (hereinafter also referred to as "compound (6)"). Examples of the compound (5) include the following boronic acid (5a), boronic acid ester (5b), trifluoroborate (5c), and cyclic triol borate (5d).

[0115] TIFF0007734129000018.tif28134

[0116] Compound (4) can be a commercially available product, but it may also be produced by a known method, a method described in the Examples, or a method similar thereto, in appropriate combination as needed. Examples of palladium catalysts include tetrakis(triphenylphosphine)palladium(0), palladium(II) acetate, tris(dibenzylideneacetone)dipalladium(0), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II). In step 3, a phosphine ligand may be used, if necessary. Examples of the phosphine ligand include triphenylphosphine, tris(2-methylphenyl)phosphine, tri(2-furyl)phosphine, tri-tert-butylphosphine, (4-dimethylaminophenyl)di-tert-butylphosphine (Amphos), 2-[di(tert-butyl)phosphino]-1,1'-biphenyl (JohnPhos), 2-[di(tert-butyl)phosphino]-2'-N,N-dimethylamino-1,1'-biphenyl (tBuDavePhos), 2-(diphenylphosphine)-2'-N,N-dimethylamino-1,1'-biphenyl (tBuDavePhos), and the like. Examples include 2-(dicyclohexylphosphino)-1,1'-biphenyl (CyJohnPhos), 2-(dicyclohexylphosphino)-2'-N,N-dimethylamino-1,1'-biphenyl (DavePhos), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (XPhos), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). Examples of the base include sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, tripotassium phosphate, potassium fluoride, cesium fluoride, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, N,N-diisopropylethylamine, triethylamine, and the like. The reaction solvent is not particularly limited as long as it does not interfere with the reaction, and examples thereof include tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane, toluene, methanol, ethanol, acetonitrile, water, and the like. The reaction solvent may be a single solvent or a mixed solvent of two or more solvents. Examples of mixed solvents include a combination of methanol and water, a combination of ethanol and water, a combination of toluene and water, and a combination of 1,4-dioxane and water. The amount of compound (5) used is usually 1 to 3 moles, preferably 1 to 2 moles, per mole of compound (4). The amount of the palladium catalyst used is usually 0.01 to 0.5 mol, preferably 0.03 to 0.2 mol, per 1 mol of compound (4). The amount of the base used is usually 1 to 10 moles, preferably 1 to 3 moles, per mole of compound (4). The reaction temperature is usually 20 to 160°C, preferably 20 to 120°C. The reaction time is usually 10 minutes to 24 hours, preferably 30 minutes to 5 hours.

[0117] Step 4: Compound (6) is amidated with compound (2) in the presence of a base catalyst to give the compound of formula (I). Compound (2) can be a commercially available product, but may also be prepared by a known method, a method described in the Examples, or a method similar thereto, suitably combining these methods as necessary. Examples of the base catalyst include 1,5,7-triazabicyclo[4.4.0]dec-5-ene, 1,8-diazabicyclo[5.4.0]-7-undecene (DBU), sodium methoxide, and the like. The reaction solvent is not particularly limited as long as it does not interfere with the reaction. Examples of the reaction solvent include toluene, 2-methyltetrahydrofuran, tetrahydrofuran, 1,2-dimethoxyethane, 1,4-dioxane, dichloromethane, chloroform, ethyl acetate, acetonitrile, and dimethyl sulfoxide. Toluene, 2-methyltetrahydrofuran, and tetrahydrofuran are particularly preferred. The amount of compound (2) used is usually 1 to 20 moles, preferably 1 to 10 moles, per mole of compound (6). The amount of the base catalyst used is usually 0.01 to 1 mole, preferably 0.1 to 0.6 mole, per mole of compound (6). The reaction temperature is usually 20 to 160°C, preferably 40 to 110°C. The reaction time is usually 1 to 48 hours, preferably 5 to 48 hours.

[0118] Production Method 3: Production Method of Compounds of Formula (I) (Part 3)

[0119] TIFF0007734129000019.tif46146

[0120] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , W and X are as defined above; M is a boronic acid, a boronic acid ester, a trifluoroborate salt, a cyclic triol borate salt, or the like; LG represents a leaving group such as a halogen atom or a trifluoromethanesulfonyloxy group.

[0121] Step 5: According to a method similar to step 2 of production method 1, compound (1) and compound (4) are subjected to a coupling reaction in the presence of a palladium catalyst and a base to obtain a compound of formula (7) (hereinafter also referred to as "compound (7)").

[0122] Step 6: According to a method similar to that of Step 1 of Production Method 1, compound (7) is reacted with compound (2) in the presence of a condensing agent to obtain a compound of formula (I).

[0123] Production method 4: Production method of compound of formula (7)

[0124] TIFF0007734129000020.tif36117

[0125] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 and W has the same meaning as above, R a is C 1-6 represents an alkyl group.

[0126] Step 7: Compound (6) is hydrolyzed in the presence of a base to give compound (7). Examples of the base include lithium hydroxide, sodium hydroxide, potassium hydroxide, and the like. The reaction solvent is not particularly limited as long as it does not interfere with the reaction, and examples thereof include methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, tert-butanol, and water, with methanol, ethanol, and water being preferred. The reaction solvent may be a single solvent or a mixed solvent of two or more solvents. Examples of mixed solvents include a combination of methanol and water, and a combination of ethanol and water. The amount of the base used is usually 1 mole to a large excess relative to 1 mole of compound (6). The reaction temperature is usually 0 to 160°C, preferably 0 to 130°C. The reaction time is usually 0.5 to 48 hours, preferably 10 minutes to 5 hours.

[0127] Production method 5: Production method of compound of formula (12)

[0128] The compound of formula (12) is a compound of formula (I) in which X is a group of general formula (II) (in formula (II), L 1 is a single bond, ring Y is a group of general formula (III), and L 2 is a single bond and p is 1).

[0129] TIFF0007734129000021.tif77144

[0130] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 8 , ring A, ring Z, m, and n are as defined above; PG is an amine protecting group, LG represents a leaving group such as a halogen atom or a trifluoromethanesulfonyloxy group.

[0131] Step 8: According to a method similar to step 1 of production method 1, compound (7) is reacted with a compound of formula (8) (hereinafter also referred to as "compound (8)") in the presence of a condensing agent to obtain a compound of formula (9) (hereinafter also referred to as "compound (9)"). Examples of the compound (8) include azetidine (8a), pyrrolidine (8b-1), pyrrolidine (8b-2), and piperidine (8c) shown below.

[0132] TIFF0007734129000022.tif31147

[0133] The PG (amine protecting group) is not particularly limited as long as it has the function, and examples thereof include a benzyl group, a 4-methoxybenzyl group, a 2,4-dimethoxybenzyl group, a 3,4-dimethoxybenzyl group, a trityl group, a methoxycarbonyl group, an ethoxycarbonyl group, a propyloxycarbonyl group, a tert-butoxycarbonyl group, and a benzyloxycarbonyl group, with a tert-butoxycarbonyl group and a 4-methoxybenzyl group being particularly preferred.

[0134] Step 9: Compound (9) is deprotected under acidic conditions or hydrogenation conditions to obtain a compound of formula (10) (hereinafter also referred to as "compound (10)").

[0135] Deprotection under acidic conditions Examples of the acid used under acidic conditions include hydrogen chloride, hydrochloric acid, sulfuric acid, trifluoroacetic acid, acetic acid, formic acid, p-toluenesulfonic acid, methanesulfonic acid, and pyridinium p-toluenesulfonate. The reaction solvent is not particularly limited as long as it does not interfere with the reaction, and examples thereof include tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, acetonitrile, ethyl acetate, toluene, water, and the like. The amount of the acid used is usually 0.01 mole to a large excess relative to 1 mole of compound (9). The reaction temperature is usually 0 to 100°C, preferably 0 to 40°C. The reaction time is usually 10 minutes to 24 hours, preferably 10 minutes to 5 hours.

[0136] Deprotection under hydrogenation conditions A catalyst is used under hydrogenation conditions, and examples of the catalyst include 5% palladium on activated carbon, 10% palladium on activated carbon, 20% palladium hydroxide on activated carbon, Raney nickel, platinum, and platinum oxide. The reaction solvent is not particularly limited as long as it does not interfere with the reaction, and examples thereof include methanol, ethanol, 1-propanol, 2-propanol, tetrahydrofuran, 1,4-dioxane, toluene, and ethyl acetate. The amount of the catalyst used is usually 0.01 to 1 mole, preferably 0.05 to 0.2 mole, per mole of compound (9). The reaction temperature is usually 0 to 100°C, preferably 10 to 40°C. The reaction time is usually 10 minutes to 24 hours, preferably 30 minutes to 5 hours.

[0137] Step 10: Compound (10) is reacted with a compound of formula (11) (hereinafter also referred to as "compound (11)") in the presence of a base to obtain compound (12). Examples of compound (11) include pyridine (11a), pyridine (11b), pyrimidine (11c), pyrazine (11d), pyrimidine (11e), pyridazine (11f), thiazole (11g), thiadiazole (11h), oxazole (11i), pyrazole (11j), imidazole (11k), imidazole (11l), tetrazole (11m), pyrazole (11n), and tetrazole (11o), as shown below.

[0138] TIFF0007734129000023.tif77137

[0139] Examples of the base include N,N-diisopropylethylamine, triethylamine, sodium carbonate, potassium carbonate, cesium carbonate, sodium hydrogencarbonate, tripotassium phosphate, potassium fluoride, cesium fluoride, sodium tert-butoxide, potassium tert-butoxide, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium hydride, and potassium hydride. The reaction solvent is not particularly limited as long as it does not interfere with the reaction. Examples of the reaction solvent include N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran, 1,4-dioxane, dichloromethane, chloroform, dimethyl sulfoxide, acetonitrile, ethyl acetate, toluene, methanol, ethanol, and water. N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide are particularly preferred. The amount of compound (11) used is usually 1 to 3 moles, preferably 1 to 2 moles, per mole of compound (10). The amount of the base used is usually 1 to 10 moles, preferably 1 to 3 moles, per mole of compound (10). The reaction temperature is usually 0 to 200°C, preferably 0 to 160°C. The reaction time is usually 10 minutes to 24 hours, preferably 30 minutes to 10 hours.

[0140] Production method 6: Production method of compound of formula (14)

[0141] The compound of formula (14) is a compound of formula (I) in which X is a group of general formula (II) (in formula (II), L 1 is a single bond, ring Y is a group of general formula (III), and L 2 is a single bond and p is 1).

[0142] TIFF0007734129000024.tif30133

[0143] (In the formula, R 1 , R 2 , R 3 , R 4 , R 5 , R 7 , R 9 and rings A and m have the same meanings as defined above.

[0144] Step 11: The thiourea intermediate produced by the reaction of compound (10) with a compound of formula (13) (hereinafter also referred to as "compound (13)") is reacted with an alkylating agent to form an S-alkylisothiourea intermediate, which is then reacted with sodium azide to obtain a compound of formula (14) (hereinafter also referred to as "compound (14)").

[0145] Compound (13) may be a commercially available product, or may be prepared by a known method or a method similar thereto. Examples of alkylating agents include 1,3-propane sultone, 1,4-butane sultone, methyl iodide, ethyl iodide, dimethyl sulfate, diethyl sulfate, etc., and 1,3-propane sultone is particularly preferred. When 1,3-propane sultone is used as the alkylating agent, it is preferable to inactivate excess 1,3-propane sultone by adding a base before reacting with sodium azide. Examples of the base include triethylamine, N,N-diisopropylethylamine, pyridine, etc., with triethylamine being particularly preferred. The alkylating agent and the base may be added simultaneously. The reaction solvent is not particularly limited as long as it does not interfere with the reaction. Examples of the reaction solvent include acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, tetrahydrofuran, 1,4-dioxane, ethyl acetate, toluene, etc., and acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone are particularly preferred. The amount of compound (13) used is usually 1 to 3 moles, preferably 1 to 2 moles, per mole of compound (10). The amount of the alkylating agent used is usually 1 to 5 moles, preferably 1 to 3 moles, per mole of compound (10). The amount of the base used is usually 1 to 10 moles, preferably 1 to 6 moles, per mole of compound (10). The amount of sodium azide used is usually 1 to 20 moles, preferably 1 to 12 moles, per mole of compound (10). The reaction temperature is usually 20°C to 160°C, preferably 100°C, after the addition of compound (13); usually 20°C to 160°C, preferably 100°C, after the addition of the alkylating agent; usually 20°C to 160°C, preferably 100°C, after the addition of the base; and usually 20°C to 160°C, preferably 100°C, after the addition of sodium azide. The reaction time after the addition of compound (13) is usually 10 minutes to 24 hours, preferably 30 minutes to 8 hours; after the addition of the alkylating agent, it is usually 10 minutes to 72 hours, preferably 1 hour to 16 hours; after the addition of the base, it is usually 5 minutes to 1 hour, preferably 30 minutes to 1 hour; and after the addition of sodium azide, it is usually 10 minutes to 72 hours, preferably 1 hour to 12 hours.

[0146] Next, a pharmaceutical composition containing the compound of the present invention and an H-PGDS inhibitor will be described.

[0147] "H-PGDS" refers to hematopoietic PGD synthase.

[0148] "Inhibiting H-PGDS" means eliminating or attenuating the activity of H-PGDS as a prostaglandin D synthase, for example, inhibiting the activity of H-PGDS under the conditions described in Example 222 below.

[0149] The term "H-PGDS inhibitor" refers to a drug for inhibiting H-PGDS.

[0150] The term "pharmaceutical composition for treating or preventing a disease associated with H-PGDS" refers to a pharmaceutical composition for treating or preventing a disease associated with H-PGDS by inhibiting H-PGDS.

[0151] Examples of "diseases involving H-PGDS" include asthma, chronic obstructive pulmonary disease, allergic rhinitis, sinusitis, eosinophilic pneumonia, atherosclerosis, rheumatoid arthritis, cystic fibrosis, actinic keratosis, chronic urticaria, dermatitis, muscular dystrophy, sarcopenia, disuse muscle atrophy, muscle injury, wounds, dermatomyositis, amyotrophic lateral sclerosis, cerebral infarction, myocardial infarction, ischemic bowel disease, ischemic kidney disease, ischemic gastric disease, ischemic liver disease, diabetic limb ischemia, and Buerger's disease.

[0152] The pharmaceutical compositions and inhibitors of the present invention can be provided as formulations.

[0153] The "preparation" may contain a pharmaceutically acceptable carrier together with the compound of the present invention. The formulation can be produced using formulation techniques commonly used in the pharmaceutical field.

[0154] Examples of "pharmaceutically acceptable carriers" include solvents (e.g., purified water, ethanol, propylene glycol, macrogol, sesame oil, corn oil, olive oil), excipients (e.g., lactose, sucrose, D-mannitol, starch, corn starch, crystalline cellulose, light anhydrous silicic acid), disintegrants (e.g., starch, carboxymethylcellulose, carboxymethylcellulose calcium, carboxymethylstarch sodium, L-hydroxypropylcellulose), binders (e.g., crystalline cellulose, sucrose, D-mannitol, dextrin, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, starch, sucrose, gelatin, methylcellulose, carboxymethylcellulose sodium), lubricants (e.g., magnesium stearate, calcium stearate, talc, colloidal silica), wetting agents (e.g., propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate, polyoxyethylene glycol monolaurate, PEG-100 stea ... Examples of suitable additives include sodium lauryl ether), antioxidants (e.g., sodium sulfite, potassium sulfite, ascorbic acid, α-tocopherol), suspending agents (stearyl triethanolamine, sodium lauryl sulfate, lauryl aminopropionic acid, lecithin, benzalkonium chloride, benzethonium chloride, glycerin monostearate, polyvinyl alcohol, polyvinylpyrrolidone, sodium carboxymethylcellulose, methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose), preservatives (e.g., ethyl parahydroxybenzoate, chlorobutanol, benzyl alcohol, sodium dehydroacetate, sorbic acid, potassium sorbate), buffers (e.g., sodium hydrogen phosphate, sodium acetate, sodium carbonate, sodium citrate), and solubilizing agents (e.g., propylene glycol, D-mannitol, benzyl benzoate, ethanol, triethanolamine, sodium carbonate, sodium citrate).

[0155] The formulation can be in various dosage forms depending on the intended use. The formulation may be solid or liquid. The formulation may also be oral or topical. Examples of formulations include tablets, capsules, powders, granules, liquids, suppositories, ointments, injections, and infusions.

[0156] The content of the compound of the present invention in the formulation can be appropriately selected depending on the application. For example, in the case of an oral formulation, the compound of the present invention can be blended as an active ingredient in an amount of 0.1 to 100% by mass, preferably 5 to 98% by mass, based on the total mass of the formulation.

[0157] The preparation may contain a drug other than the compound of the present invention (hereinafter also referred to as a "concomitant drug"), which can be appropriately selected depending on the application. "Combined use" refers to the use of multiple active ingredients in combination. Examples of combined use include use as a combination drug, use as a kit, and administration of each active ingredient separately via the same or different administration route. [Example]

[0158] The present invention will be explained in more detail below by way of examples, but the present invention is not limited to these examples. Unless otherwise specified, the various reagents used in the examples were commercially available products. In the examples, room temperature means 1°C to 40°C. In silica gel column chromatography, unless otherwise specified, Biotage (registered trademark) SNAP Ultra Silica Cartridge or SNAP KP-Sil Cartridge manufactured by Biotage, or CHROMATOREX (registered trademark) Q-PACK SI, Q-PACK NH or Q-PACK COH manufactured by Fuji Silysia Chemical Ltd. was used as the column, and ethyl acetate / n-hexane, methanol / chloroform, or methanol / ethyl acetate was used as the mobile phase. In the reversed-phase silica gel column chromatography, a Biotage (registered trademark) SNAP Ultra C18 Cartridge manufactured by Biotage was used as the column, and a 0.1% aqueous trifluoroacetic acid solution and a 0.1% acetonitrile solution of trifluoroacetic acid were used as the mobile phase. In the reversed-phase preparative liquid chromatography, a YMC-ActusTriart C18 manufactured by YMC was used as the column, and a 0.1% aqueous trifluoroacetic acid solution and a 0.1% acetonitrile solution of trifluoroacetic acid were used as the mobile phase. In the preparative thin layer chromatography, PLC Silica gel 60 F254 manufactured by Merck was used as a TLC (silica gel plate).

[0159] 1 H-NMR was measured using a JEOL ECZ400S (400 MHz) spectrometer. Chemical shifts of NMR data were expressed in parts per million (ppm, δ) based on the residual protons in the deuterated solvent used. Mass spectra were measured using a Waters ACQUITY (registered trademark) SQD by electrospray ionization (ESI). The ESI-MS data are reported as actual measurements (found values). In the case of salts, the molecular ion peak of the free form is usually observed. The microwave reaction was carried out using Initiator (registered trademark) manufactured by Biotage.

[0160] The meanings of the abbreviations are as follows: s:singlet d: doublet t: triplet q:Quartet dd: double doublet m: multiplet br: Broad CDCl3: deuterated chloroform CD3OD: deuterated methanol DMSO-d6: Deuterated dimethyl sulfoxide DIPEA: N,N-diisopropylethylamine DMF: N,N-dimethylformamide DMSO: dimethyl sulfoxide EDC: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride NMP: N-methylpyrrolidone PdCl2(dppf):[1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) PdCl2(dppf)·CH2Cl2:[1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex Pd(PPh3)4: Tetrakis(triphenylphosphine)palladium(0) THF: tetrahydrofuran

[0161] Example 1 Synthesis of N-methyl-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [1] (hereinafter referred to as compound [1])

[0162] TIFF0007734129000025.tif2541

[0163] To a solution of 4-chloro-1H-pyrrolo[3,2-c]pyridine (76 mg) in ethanol (1.0 mL) / water (1.0 mL), N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (116 mg), potassium carbonate (90 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (13 mg) were added at room temperature, and the mixture was stirred at 80°C for 3 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (78 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:11.70(br,1H),8.59-8.45(m,1H),8.28(d,J=5.9Hz,1H),8.08(d,J=8.7Hz,2H),7. 97(d,J=8.2Hz,2H),7.56-7.54(m,1H),7.41(dd,J=5.9,0.9Hz,1H),6.81-6.79(m,1H),2.81(d,J=4.6Hz,3H). ESI-MS: 252.2 [M+H] +

[0164] Example 2 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [2] (hereinafter referred to as compound [2])

[0165] TIFF0007734129000026.tif3064

[0166] (1) Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide [2-1] (hereinafter referred to as compound [2-1])

[0167] TIFF0007734129000027.tif3055

[0168] To a solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (2.44 g) in DMF (33 mL), DIPEA (1.84 mL) and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (4.63 g) were added at room temperature, and the mixture was stirred at room temperature for 5 minutes. 2-(trans-4-aminocyclohexyl)propan-2-ol (2.01 g) was added to the reaction mixture at room temperature, and the mixture was stirred at room temperature for 30 minutes. 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was suspended in ethyl acetate / n-hexane, and the solid was collected by filtration to give the title compound (2.54 g) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:7.85(d,J=8.2Hz,2H),7.72(d,J=7.8Hz,2H),5.92(d,J=8.2 Hz,1H),4.01-3.84(m,1H),2.27-2.09(m,2H),2.03-1.84(m,2H),1.45-1.11(m,23H). ESI-MS: 388.5 [M+H] +

[0169] (2) Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [2] To a solution of 4-chloro-1H-pyrrolo[3,2-c]pyridine (770 mg) in ethanol (12.5 mL) / water (12.5 mL), compound [2-1] (2.54 g), potassium carbonate (906 mg), and [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (163 mg) were added at room temperature, and the mixture was stirred at 100°C for 2 hours under an argon atmosphere. Water was added to the reaction mixture, and the resulting solid was collected by filtration. The resulting solid was dissolved in a solution of chloroform (400 mL) / methanol (200 mL) and eluted with a strong acid cation exchange resin (H type) (Dowex TMThe extract was poured into a column packed with silica gel (50WX2, 50-100 mesh). The column was washed with a chloroform / methanol (volume ratio 2 / 1) solution and eluted with a 2M ammonia / methanol solution. The eluate was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (984 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:11.70(br,1H),8.36-8.20(m,2H),8.07(d,J=8.2Hz,2H),7.98(d,J=8.2Hz,2H),7.55(d,J=3.2Hz,1H),7. 41(d,J=5.5Hz,1H),6.79(d,J=2.7Hz,1H),4.04(s,1H),3.81-3.65(m,1H),2.00-1.74(m,4H),1.41-1.25(m,2H),1.24-0.96(m,9H). ESI-MS: 378.4 [M+H] +

[0170] Example 3 Synthesis of N-[trans-4-(hydroxymethyl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [3] (hereinafter referred to as compound [3])

[0171] TIFF0007734129000028.tif2563

[0172] The title compound was synthesized according to the method of Example 2. 1H-NMR(400MHz,DMSO-d6)δ:11.69(br,1H),8.37-8.21(m,2H),8.06(d,J=8.2Hz,2H),7.98(d,J=7.8Hz,2H),7.57-7.54(m,1H),7.41(d,J=6.4Hz,1H) ,6.86-6.72(m,1H),4.40(t,J=5.3Hz,1H),3.84-3.67(m,1H),3.23(dd,J= 5.7,5.7Hz,2H),1.95-1.69(m,4H),1.44-1.19(m,3H),1.08-0.88(m,2H). ESI-MS: 350.3 [M+H] +

[0173] Example 4 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [4] (hereinafter referred to as compound [4])

[0174] TIFF0007734129000029.tif3064

[0175] To a solution of 4-chloro-1-methyl-1H-pyrrolo[3,2-c]pyridine (14 mg) in 1,4-dioxane (1.3 mL) / water (0.30 mL), compound [2-1] (30 mg), potassium phosphate tribasic (33 mg), and PdCl(dppf) (5.7 mg) were added at room temperature and stirred at 130 °C for 30 minutes using a microwave reactor. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (9.0 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.34(d,J=5.5Hz,1H),8.28(d,J=7.8Hz,1H),8.05(d,J=8.2Hz,2H),7.97(d,J=8.2Hz,2H),7.54(d,J=3.7Hz,1H),7.5 1(d,J=5.9Hz,1H),6.79(d,J=2.7Hz,1H),4.04(s,1H),3.85(s,3H),3.7 9-3.64(m,1H),1.96-1.74(m,4H),1.41-1.25(m,2H),1.24-0.95(m,9H). ESI-MS: 392.2 [M+H] +

[0176] Example 5 Synthesis of N-cyclohexyl-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [5] (hereinafter referred to as compound [5])

[0177] TIFF0007734129000030.tif2550

[0178] (1) Synthesis of ethyl 4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzoate [5-1] (hereinafter referred to as compound [5-1])

[0179] TIFF0007734129000031.tif2546

[0180] To a solution of 4-chloro-1H-pyrrolo[3,2-c]pyridine (839 mg) in ethanol (5.5 mL) / water (5.5 mL), 4-(ethoxycarbonyl)phenylboronic acid (1.39 g), potassium carbonate (988 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (143 mg) were added at room temperature, and the mixture was stirred at 100°C for 3 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (1.19 g) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:9.14(br,1H),8.45(d,J=5.9Hz,1H),8.20(d,J=8.2Hz,2H),8.08(d,J= 7.8Hz,2H),7.39-7.28(m,2H),6.91-6.77(m,1H),4.42(q,J=7.2Hz,2H),1.43(t,J=7.1Hz,3H). ESI-MS: 267.3 [M+H] +

[0181] (2) Synthesis of N-cyclohexyl-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide [5] To a solution of compound [5-1] (40 mg) in toluene (0.30 mL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (6.3 mg) and cyclohexylamine (86 μL) were added at room temperature, and the mixture was stirred at 80° C. for 31 hours. Chloroform was added to the reaction mixture, and the mixture was purified by silica gel column chromatography to obtain the title compound (9.4 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:11.71(br,1H),8.37-8.20(m,2H),8.06(d,J=8.2Hz,2H),7.98(d,J=8.7Hz,2H),7.55(d,J=2.7Hz, 1H),7.41(d,J=5.5Hz,1H),6.79(d,J=3.2Hz,1H),3.87-3.71(m,1H),1.93-1.66(m,4H),1.65-1.57(m,1H),1.42-1.06(m,5H). ESI-MS: 320.4 [M+H] +

[0182] Examples 6 to 58 The compounds of Examples 6 to 58 shown in the table below were synthesized according to the method shown in step (2) of Example 5. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0183] [Table 1-1]

[0184]

Table 1-2

[0185]

Table 1-3

[0186]

Table 1-4

[0187]

Table 1-5

[0188]

Table 1-6

[0189]

Table 1-7

[0190]

Table 1-8

[0191]

Table 1-9

[0192]

Table 1-10

[0193]

Table 1-11

[0194] Example 59 Synthesis of N-benzyl-4-(thieno[3,2-c]pyridin-4-yl)benzamide

[59] (hereinafter referred to as compound

[59] )

[0195] TIFF0007734129000043.tif2554

[0196] (1) Synthesis of ethyl 4-(thieno[3,2-c]pyridin-4-yl)benzoate [59-1] (hereinafter referred to as compound [59-1])

[0197] TIFF0007734129000044.tif2545

[0198] To a solution of 4-chlorothieno[3,2-c]pyridine (509 mg) in ethanol (3.0 mL) / water (3.0 mL), 4-(ethoxycarbonyl)phenylboronic acid (757 mg), potassium carbonate (539 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (78.0 mg) were added at room temperature, and the mixture was stirred at 100°C under an argon atmosphere for 2 hours. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (741 mg) as a pale yellow solid. 1 H-NMR(400MHz,CDCl3)δ:8.58(d,J=5.5Hz,1H),8.21(d,J=8.7Hz,2H),7.92(d,J=8.2Hz,2H),7.84(dd,J=5.5 ,0.9Hz,1H),7.59(dd,J=5.5,0.9Hz,1H),7.54(d,J=5.5Hz,1H),4.43(q,J=7.2Hz,2H),1.44(t,J=7.1Hz,3H). ESI-MS: 284.5 [M+H] +

[0199] (2) Synthesis of N-benzyl-4-(thieno[3,2-c]pyridin-4-yl)benzamide

[59] To a solution of compound [59-1] (28 mg) in toluene (0.20 mL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (4.2 mg) and benzylamine (55 μL) were added at room temperature, and the mixture was stirred at 80° C. for 21 hours. Ethyl acetate was added to the reaction mixture, and the mixture was purified by silica gel column chromatography to obtain the title compound (31 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:9.19(t,J=5.9Hz,1H),8.54(d,J=5.5Hz,1H),8.12(d,J=5.5Hz,1H),8.07(d,J=8.2 Hz,2H),8.01-7.85(m,3H),7.66(d,J=5.0Hz,1H),7.42-7.29(m,4H),7.29-7.18(m,1H),4.52(d,J=5.9Hz,2H). ESI-MS: 345.2 [M+H] +

[0200] Example 60 Synthesis of N-(pyridin-4-ylmethyl)-4-(thieno[3,2-c]pyridin-4-yl)benzamide

[60] (hereinafter referred to as compound

[60] )

[0201] TIFF0007734129000045.tif2555

[0202] To a solution of compound [59-1] (28 mg) in toluene (0.20 mL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (4.2 mg) and 4-picolylamine (51 μL) were added at room temperature, and the mixture was stirred at 80° C. for 21 hours. Ethyl acetate was added to the reaction mixture, and the mixture was purified by silica gel column chromatography to obtain the title compound (31 mg) as a white solid. ESI-MS: 346.2 [M+H] +

[0203] Example 61 Synthesis of N-(2-hydroxypropyl)-4-(thieno[3,2-c]pyridin-4-yl)benzamide

[61] (hereinafter referred to as compound

[61] )

[0204] TIFF0007734129000046.tif2550

[0205] To a solution of compound [59-1] (28 mg) in toluene (0.20 mL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (4.2 mg) and 1-amino-2-propanol (39 μL) were added at room temperature, and the mixture was stirred at 80° C. for 21 hours. Ethyl acetate was added to the reaction mixture, and the mixture was purified by silica gel column chromatography to obtain the title compound (24 mg) as a white solid. ESI-MS: 313.2 [M+H] +

[0206] Example 62 Synthesis of N-[2-(diisopropylamino)ethyl]-4-(thieno[3,2-c]pyridin-4-yl)benzamide dihydrochloride

[62] (hereinafter referred to as compound

[62] )

[0207] TIFF0007734129000047.tif2554

[0208] To a solution of compound [59-1] (28 mg) in toluene (0.20 mL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (4.2 mg) and N,N-diisopropylethylenediamine (87 μL) were added at room temperature, and the mixture was stirred at 80 °C for 21 hours. Ethyl acetate was added to the reaction mixture, and the mixture was purified by silica gel column chromatography. A 4 M solution of hydrogen chloride in ethyl acetate was added to the resulting oil, and the resulting solid was collected by filtration to obtain the title compound (20 mg) as a white solid. ESI-MS: 382.3 [M+H] +

[0209] Example 63 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(thieno[3,2-c]pyridin-4-yl)benzamide

[63] (hereinafter referred to as compound

[63] )

[0210] TIFF0007734129000048.tif3061

[0211] To a solution of 4-chlorothieno[3,2-c]pyridine (58.0 mg) in ethanol (0.8 mL) / water (0.8 mL), compound [2-1] (120 mg), potassium carbonate (56.0 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (10.0 mg) were added at room temperature, and the mixture was stirred at 80°C for 1 hour under an argon atmosphere. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (105 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.54(d,J=5.5Hz,1H),8.32(d,J=8.2Hz,1H),8.12(dd,J=5.5,0.9Hz,1H),8.01(d,J=8.2Hz,2H),7.96(d,J=5.5 Hz,1H),7.90(d,J=8.2Hz,2H),7.70-7.61(m,1H),4.04(s,1H),3.85-3.65(m,1H),1.96-1.72(m,4H),1.42-1.25(m,2H),1.24-0.93(m,9H). ESI-MS: 395.3 [M+H] +

[0212] Example 64 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide

[64] (hereinafter referred to as compound

[64] )

[0213] TIFF0007734129000049.tif3071

[0214] (1) Synthesis of trans-4-(dibenzylamino)cyclohexan-1-ol [64-1] (hereinafter referred to as compound [64-1])

[0215] TIFF0007734129000050.tif3143

[0216] To a solution of trans-4-aminocyclohexan-1-ol (3.00 g) in ethanol (50.0 mL), benzyl bromide (6.80 mL) and sodium bicarbonate (8.75 g) were added at room temperature, and the mixture was stirred at 80°C for 45 minutes. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (2.00 g) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:7.37-7.35(m,4H),7.30-7.26(m,4H),7.22-7.18(m,2H),3.64(s,4H),3.57-3.5 2(m,1H),2.56-2.48(m,1H),2.14-1.97(m,2H),1.94-1.88(m,2H),1.48-1.38(m,2H),1.23-1.14(m,2H). ESI-MS: 296.3 [M+H] +

[0217] (2) Synthesis of tert-butyl 2-{[trans-4-(dibenzylamino)cyclohexyl]oxy}acetate [64-2] (hereinafter referred to as compound [64-2])

[0218] TIFF0007734129000051.tif3054

[0219] To a solution of compound [64-1] (2.0 g) in DMF (13 mL), 60% sodium hydride (320 mg) and tert-butyl bromoacetate (1.5 mL) were added at room temperature, and the mixture was stirred at 55°C for 2 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (700 mg) as a yellow oil. 1 H-NMR(400MHz,CDCl3)δ:7.36-7.34(m,4H),7.30-7.26(m,4H),7.21-7.18(m,2H),3.96(s,2H),3.60(s ,4H),3.27-3.20(m,1H),2.56-2.49(m,1H),2.10-2.07(m,2H),1.93-1.90(m,2H),1.46-1.43(m,13H). ESI-MS: 410.4 [M+H] +

[0220] (3) Synthesis of 1-{[trans-4-(dibenzylamino)cyclohexyl]oxy}-2-methylpropan-2-ol [64-3] (hereinafter referred to as compound [64-3])

[0221] TIFF0007734129000052.tif3053

[0222] To a solution of compound [64-2] (700 mg) in THF (3.40 mL), a 3 M solution of methylmagnesium bromide in diethyl ether (1.70 mL) was added at 0°C and stirred at room temperature for 3 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (285 mg) as a yellow oil. 1H-NMR(400MHz,CDCl3)δ:7.37-7.35(m,4H),7.31-7.27(m,4H),7.22-7.19(m,2H),3.61(s,4H),3.24(s,2H),3. 22-3.15(m,1H),2.56-2.50(m,1H),2.08-2.04(m,2H),1.93-1.90(m,2H),1.40-1.31(m,2H),1.20-1.10(m,8H). ESI-MS: 368.4 [M+H] +

[0223] (4) Synthesis of 1-[(trans-4-aminocyclohexyl)oxy]-2-methylpropan-2-ol [64-4] (hereinafter referred to as compound [64-4])

[0224] TIFF0007734129000053.tif2046

[0225] To a solution of compound [64-3] (285 mg) in ethanol (1.50 mL), 20% palladium hydroxide on activated carbon (21.0 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 4 hours. The reaction mixture was filtered and concentrated under reduced pressure to give the title compound (140 mg) as a black oil. 1 H-NMR(400MHz, CDCl3)δ:3.27-3.21(m,3H),2.74-2.68(m,1H),2.03-1.99(m,2H),1.89-1.86(m,2H),1.34-1.08(m,10H). ESI-MS: 188.3 [M+H] +

[0226] (5) Synthesis of ethyl 4-(furo[3,2-c]pyridin-4-yl)benzoate [64-5] (hereinafter referred to as compound [64-5])

[0227] TIFF0007734129000054.tif2546

[0228] To a solution of 4-chlorofuro[3,2-c]pyridine (2.00 g) in ethanol (13.0 mL) / water (13.0 mL), 4-(ethoxycarbonyl)phenylboronic acid (2.65 g), potassium carbonate (2.36 g), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (84.0 mg) were added at room temperature, and the mixture was stirred at 100°C for 3 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (3.20 g) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:8.62(d,J=5.5Hz,1H),8.24-8.18(m,2H),8.05-8.03(m,2H),7.74(d,J=2.3 Hz,1H),7.48(dd,J=5.9,0.9Hz,1H),7.08-7.07(m,1H),4.43(q,J=7.2Hz,2H),1.44(t,J=7.1Hz,3H). ESI-MS: 268.3 [M+H] +

[0229] (6) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide

[64] To a solution of compound [64-5] (20 mg) in toluene (150 μL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (3.2 mg) and compound [64-4] (71 mg) were added at room temperature, and the mixture was stirred at 80° C. for 24 hours. Chloroform was added to the reaction mixture, and the mixture was purified by silica gel column chromatography to obtain the title compound (4.2 mg) as a brown solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.33(d,J=7.8Hz,1H),8.24 (d,J=2.7Hz,1H),8.08(dd,J=6.9,1.8Hz,2H),8.03-7.98(m,2H),7.73(d,J=5. 5Hz,1H),7.37-7.36(m,1H),3.86-3.72(m,1H),3.16-3.11(m,3H),2.03-2.01 (m,2H),1.90-1.87(m,2H),1.46-1.34(m,2H),1.31-1.20(m,2H),1.06(s,6H). ESI-MS: 409.4 [M+H] +

[0230] Examples 65 to 97 The compounds of Examples 65 to 97 shown in the table below were synthesized according to the method shown in Step (6) of Example 64. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0231] [Table 2-1]

[0232] [Table 2-2]

[0233] [Table 2-3]

[0234] [Table 2-4]

[0235] [Table 2-5]

[0236] [Table 2-6]

[0237] [Table 2-7]

[0238] Example 98 Synthesis of N-[2-(diisopropylamino)ethyl]-4-(furo[3,2-c]pyridin-4-yl)benzamide dihydrochloride

[98] (hereinafter referred to as compound

[98] )

[0239] TIFF0007734129000062.tif2554

[0240] To a solution of compound [64-5] (150 mg) in toluene (1.12 mL), 1,5,7-triazabicyclo[4.4.0]dec-5-ene (23.4 mg) and N,N-diisopropylethylenediamine (488 μL) were added at room temperature and stirred at 80 °C for 24 hours. Chloroform was added to the reaction mixture, and the mixture was purified by silica gel column chromatography. A 4 M solution of hydrogen chloride in ethyl acetate was added to the resulting oil, and the resulting solid was collected by filtration to obtain the title compound (154 mg) as a yellow solid. ESI-MS: 366.3 [M+H] +

[0241] Example 99 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-tetrazol-5-yl)piperidin-4-yl]benzamide

[99] (hereinafter referred to as compound

[99] )

[0242] TIFF0007734129000063.tif3667

[0243] (1) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)benzoic acid [99-1] (hereinafter referred to as compound [99-1])

[0244] TIFF0007734129000064.tif2541

[0245] To a solution of compound [64-5] (3.50 g) in methanol (44.0 mL), 2 M aqueous sodium hydroxide solution (33.0 mL) was added at room temperature, and the mixture was stirred for 10 minutes at 100° C. 2 M hydrochloric acid (33.0 mL) was added to the reaction mixture, and the resulting solid was collected by filtration and dried under reduced pressure at 40° C. to obtain the title compound (3.42 g) as a gray solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.72-8.66(m,1H),8.43-8.36(m,1H),8.17-8.12(m,4H),8.02-7.91(m,1H),7.49-7.45(m,1H). ESI-MS: 240.3 [M+H] +

[0246] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-tetrazol-5-yl)piperidin-4-yl]benzamide

[99] To a solution of compound [99-1] (10.0 mg) in DMF (150 μL), DIPEA (8.00 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (20.0 mg), and 1-(1-methyl-1H-1,2,3,4-tetrazol-5-yl)piperidin-4-amine dihydrochloride (14.0 mg) were added at room temperature, and the mixture was stirred at room temperature for 22 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then 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 column chromatography to obtain the title compound (13.0 mg) as a pink solid. 1H-NMR(400MHz,CD3OD)δ:8.53(d,J=5.5Hz,1H),8.04-7.99(m,5H),7.63(d,J=5.9Hz,1H),7.20(d,J=2.3Hz,1H ),4.22-4.14(m,1H),3.94(s,3H),3.76-3.73(m,2H),3.25-3.18(m,2H),2.13-2.09(m,2H),1.92-1.82(m,2H). ESI-MS: 404.4 [M+H] +

[0247] Examples 100 to 117 The compounds of Examples 100 to 117 shown in the table below were synthesized according to the method shown in Step (2) of Example 99. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0248] [Table 3-1]

[0249] [Table 3-2]

[0250] [Table 3-3]

[0251] [Table 3-4]

[0252] Example 118 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyridin-2-yl)piperidin-4-yl]benzamide

[0118] (hereinafter referred to as compound

[0118] )

[0253] TIFF0007734129000069.tif3157

[0254] To a solution of compound [99-1] (20.0 mg) in DMF (300 μL), DIPEA (16.0 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (40.0 mg), and 1-(pyridin-2-yl)piperidin-4-amine (19.4 mg) were added at room temperature, and the mixture was stirred at room temperature for 24 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (13.0 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.55(d,J=5.5Hz,1H),8.39(d,J=8.2Hz,1H),8.21(d,J=2.3H) z,1H),8.10-8.03(m,3H),7.99(dd,J=6.9,1.8Hz,2H),7.69(dd,J=5.9,0.9Hz,1H),7.57- 7.43(m,1H),7.34-7.33(m,1H),6.85(d,J=8.7Hz,1H),6.57(dd,J=6.6,4.8Hz,1H),4.31- 4.28(m,2H),4.16-4.07(m,1H),2.95-2.89(m,2H),1.85-1.83(m,2H),1.58-1.49(m,2H). ESI-MS: 399.4 [M+H] +

[0255] Example 119 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(2,2,2-trifluoroethyl)amino]cyclohexyl}benzamide

[0119] (hereinafter referred to as compound

[0119] )

[0256] TIFF0007734129000070.tif3064

[0257] (1) Synthesis of {trans-4-[(2,2,2-trifluoroethyl)amino]cyclohexyl}carbamate benzyl [119-1] (hereinafter referred to as compound [119-1])

[0258] TIFF0007734129000071.tif2560

[0259] To a solution of trans-1,4-cyclohexanediamine (228 mg) in water (2.00 mL) and 1,4-dioxane (18.0 mL), potassium carbonate (553 mg) and benzyl chloroformate (284 μL) were added at 0°C and stirred at room temperature for 19 hours. The reaction mixture was concentrated under reduced pressure, and water was added to the resulting residue, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the resulting residue in 1,4-dioxane (6.30 mL), DIPEA (220 μL) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (91.0 μL) were added at room temperature, followed by stirring at room temperature for 19 hours. The reaction mixture was concentrated under reduced pressure, and water was added to the resulting residue, followed by extraction with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (132 mg) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:7.36-7.30(m,5H),5.08(s,2H),4.58-4.57(m,1H)3. 48-3.47(m,1H),3.19(q,J=9.6Hz,2H),2.04-1.94(m,4H),1.29-1.10(m,4H). ESI-MS: 331.3 [M+H] +

[0260] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(2,2,2-trifluoroethyl)amino]cyclohexyl}benzamide

[0119] To a solution of compound [119-1] (117 mg) in ethanol (1.20 mL), 10% palladium on activated carbon (19.0 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 23 hours. The reaction mixture was filtered and concentrated under reduced pressure. To a solution of the resulting residue in DMF (300 μL), DIPEA (16.0 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (40.0 mg), and compound [99-1] (20.0 mg) were added at room temperature, and the mixture was stirred at room temperature for 21 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (4.50 mg) as a pink solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.5Hz,1H),8.33(d,J=8.2Hz,1H),8.24(d, J=2.3Hz,1H),8.08(dd,J=6.9,1.8Hz,2H),8.04-7.94(m,2H),7.72(dd,J=5.7,1. 1Hz,1H),7.36-7.35(m,1H),3.86-3.68(m,1H),3.29-3.19(m,2H),2.41-2.39(m, 1H),2.23-2.18(m,1H),1.94-1.84(m,4H),1.42-1.32(m,2H),1.16-1.06(m,2H). ESI-MS: 418.4 [M+H] +

[0261] Example 120 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(hydroxymethyl)cyclohexyl]benzamide

[0120] (hereinafter referred to as compound

[0120] )

[0262] TIFF0007734129000072.tif2561

[0263] To a solution of compound [99-1] (191 mg) in DMF (3.20 mL), DIPEA (150 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (377 mg), and (trans-4-aminocyclohexyl)methanol (134 mg) were added at room temperature, and the mixture was stirred at room temperature for 17 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (280 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.34(d,J=7.8Hz,1H),8.25(d,J=2.3Hz,1H),8.08(dd,J=6.4,1.8Hz,2H),8.02-8.00(m,2H),7.74( d,J=5.9Hz,1H),7.37-7.36(m,1H),3.79-3.71(m,1H),3.24-3.22(m,2H),1 .89-1.87(m,2H),1.80-1.77(m,2H),1.40-1.31(m,3H),1.03-0.94(m,2H). ESI-MS: 351.3 [M+H] +

[0264] Example 121 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(1-hydroxyethyl)cyclohexyl]benzamide

[0121] (hereinafter referred to as compound

[0121] )

[0265] TIFF0007734129000073.tif3063

[0266] To a solution of compound

[0120] (250 mg) in dichloromethane (2.40 mL), 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) (394 mg) was added at room temperature, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. A 3M solution of methylmagnesium bromide in diethyl ether (880 μL) was added to a solution of the resulting residue in THF (3.00 mL) at 0°C, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (47.0 mg) as a pink solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.56(d,J=5.9Hz,1H),8.33-8.27(m,1H),8.21(d,J=2.3Hz,1H),8.09-8.03(m,2H),8.01-7.95(m,2H),7.69( dd,J=5.8,1.0Hz,1H),7.34-7.33(m,1H),4.28-4.27(m,1H),3.75-3.66(m,1H),3.35-3.33(m,1H),1.90-1.67(m,4H),1.36-1.02(m,8H). ESI-MS: 365.3 [M+H] +

[0267] Example 122 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[6-(2-hydroxypropan-2-yl)spiro[3.3]heptan-2-yl]benzamide

[0122] (hereinafter referred to as compound

[0122] )

[0268] TIFF0007734129000074.tif3161

[0269] (1) Synthesis of methyl 6-(dibenzylamino)spiro[3.3]heptane-2-carboxylate [122-1] (hereinafter referred to as compound [122-1])

[0270] TIFF0007734129000075.tif3634

[0271] To a solution of methyl 6-oxospiro[3.3]heptane-2-carboxylate (1.00 g) in THF (50.0 mL), dibenzylamine (1.17 mL) was added at room temperature and stirred for 2 hours. Sodium triacetoxyborohydride (1.90 g) and acetic acid (34.0 μL) were added to the reaction mixture at room temperature, and the mixture was stirred for 19 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The resulting residue was purified by silica gel column chromatography to give the title compound (530 mg) as a yellow oil. ESI-MS: 351.3 [M+H] +

[0272] (2) Synthesis of 2-[6-(dibenzylamino)spiro[3.3]heptan-2-yl]propan-2-ol [122-2] (hereinafter referred to as compound [122-2])

[0273] TIFF0007734129000076.tif3636

[0274] To a solution of compound [122-1] (530 mg) in diethyl ether (20.0 mL), a 3M solution of methylmagnesium bromide in diethyl ether (6.06 mL) was added at 0°C and stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (306 mg) as a white solid. ESI-MS: 351.4 [M+H] +

[0275] (3) Synthesis of 2-(6-aminospiro[3.3]heptan-2-yl)propan-2-ol [122-3] (hereinafter referred to as compound [122-3])

[0276] TIFF0007734129000077.tif2534

[0277] To a solution of compound [122-2] (306 mg) in ethanol (2.00 mL), 20% palladium hydroxide on activated carbon (30.0 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 5 hours. The reaction mixture was filtered and concentrated under reduced pressure to give the title compound (142 mg) as a brown oil. ESI-MS: 170.3 [M+H] +

[0278] (4) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[6-(2-hydroxypropan-2-yl)spiro[3.3]heptan-2-yl]benzamide

[0122] To a solution of compound [99-1] (20 mg) in DMF (0.30 mL), DIPEA (16 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (40 mg), and compound [122-3] (18 mg) were added at room temperature, and the mixture was stirred at room temperature for 22 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (8.2 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.64(d,J=5.9Hz,1H),8.56-8.51(m,1H),8.22-8.20(m,1H),8.11-8.02(m,2H),8.01-7.94(m,2H),7.70-7.69(m ,1H),7.34-7.33(m,1H),4.32-4.26(m,1H),3.96(s,1H),2.42-2.37(m ,1H),2.12-2.06(m,4H),1.99-1.88(m,4H),0.94(s,3H),0.92(s,3H). ESI-MS: 391.4 [M+H] +

[0279] Example 123 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyridin-4-yl)piperidin-4-yl]benzamide

[0123] (hereinafter referred to as compound

[0123] )

[0280] TIFF0007734129000078.tif3159

[0281] To a solution of compound [99-1] (35 mg) in DMF (0.50 mL), DIPEA (85 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (56 mg), and 4-amino-1-(pyridin-4-yl)piperidine dihydrochloride (20 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (10 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.55(d,J=5.5Hz,1H),8.40(d,J=7.8Hz,1H),8.21(d ,J=2.3Hz,1H),8.11(d,J=6.4Hz,2H),8.06(d,J=8.7Hz,2H),7.99(d,J=8.2Hz,2H ),7.73-7.65(m,1H),7.33(d,J=1.1Hz,1H),6.82(d,J=6.9Hz,2H),4.13-4.03(m, 1H),3.99-3.96(m,2H),3.00-2.94(m,2H),1.91-1.78(m,2H),1.60-1.51(m,2H). ESI-MS: 399.3 [M+H] +

[0282] Example 124 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0124] (hereinafter referred to as compound

[0124] )

[0283] TIFF0007734129000079.tif3063

[0284] To a solution of 4-chlorofuro[3,2-c]pyridine (336 mg) in ethanol (5.20 mL) / water (5.20 mL), compound [2-1] (808 mg), potassium carbonate (375 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (54.2 mg) were added at room temperature, and the mixture was stirred at 80°C for 6 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (588 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.5Hz,1H),8.32(d,J=7.8Hz,1H),8.23(d,J=2.3Hz,1H),8.08(d,J=8.7Hz,2H),8.01(d,J=8.7Hz, 2H),7.72(d,J=5.5Hz,1H),7.39-7.33(m,1H),4.04(s,1H),3.81-3.66(m,1H),2.00-1.70(m,4H),1.47-1.25(m,2H),1.24-0.92(m,9H). ESI-MS: 379.4 [M+H] +

[0285] Example 125 Synthesis of 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0125] (hereinafter referred to as compound

[0125] )

[0286] TIFF0007734129000080.tif3063

[0287] (1) Synthesis of methyl 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)benzoate [125-1] (hereinafter referred to as compound [125-1])

[0288] TIFF0007734129000081.tif2541

[0289] To a solution of 4-chlorofuro[3,2-c]pyridine (154 mg) in methanol (1.65 mL) / water (1.65 mL), 2-fluoro-4-(methoxycarbonyl)phenylboronic acid (257 mg), potassium carbonate (180 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (26.0 mg) were added at room temperature, and the mixture was stirred at 80°C for 1 hour under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (242 mg) as a pale yellow solid. 1 H-NMR(400MHz,CDCl3)δ:8.64(d,J=5.5Hz,1H),7.99(dd,J=8.0,1.6Hz,1H),7.94-7.85(m ,2H),7.71(d,J=2.3Hz,1H),7.52(dd,J=5.9,0.9Hz,1H),6.89-6.80(m,1H),3.98(s,3H). ESI-MS: 272.2 [M+H] +

[0290] (2) Synthesis of 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)benzoic acid [125-2] (hereinafter referred to as compound [125-2])

[0291] TIFF0007734129000082.tif2541

[0292] To a solution of compound [125-1] (242 mg) in methanol (8.8 mL), 2 M aqueous sodium hydroxide solution (4.4 mL) was added at room temperature, and the mixture was stirred at 60° C. for 20 minutes. The reaction mixture was concentrated under reduced pressure, and 2 M hydrochloric acid was added. The resulting solid was collected by filtration, washed with water, and then dried under reduced pressure to obtain the title compound (191 mg) as a gray solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.62(d,J=5.5Hz,1H),8.19(d,J=2.3Hz,1H),7.93(dd,J =8.2,1.4Hz,1H),7.90-7.81(m,2H),7.79(dd,J=5.9,0.9Hz,1H),7.08-6.94(m,1H). ESI-MS: 258.2 [M+H] +

[0293] (3) Synthesis of 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0125] To a solution of compound [125-2] (51 mg) in DMF (1.0 mL), DIPEA (37 μL) and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (94 mg) were added at room temperature, and the mixture was stirred at room temperature for 5 minutes. 2-(trans-4-aminocyclohexyl)propan-2-ol (41 mg) was added to the reaction mixture at room temperature, and the mixture was stirred at room temperature for 22 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (65 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.61(d,J=5.5Hz,1H),8.40(d,J=7.8Hz,1H),8.18(d,J=2.3Hz,1H),7.91-7.75(m,4 H),7.01-6.90(m,1H),4.03(s,1H),3.85-3.64(m,1H),1.99-1.73(m,4H),1.40-1.24(m,2H),1.25-0.92(m,9H). ESI-MS: 397.4 [M+H] +

[0294] Example 126 Synthesis of 2-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0126] (hereinafter referred to as compound

[0126] )

[0295] TIFF0007734129000083.tif3062

[0296] (1) Synthesis of methyl 2-fluoro-4-(furo[3,2-c]pyridin-4-yl)benzoate [126-1] (hereinafter referred to as compound [126-1])

[0297] TIFF0007734129000084.tif3050

[0298] To a solution of 4-chlorofuro[3,2-c]pyridine (154 mg) in methanol (1.65 mL) / water (1.65 mL), 3-fluoro-4-(methoxycarbonyl)phenylboronic acid (257 mg), potassium carbonate (180 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (26.0 mg) were added at room temperature, and the mixture was stirred at 80°C for 2 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (208 mg) as a pale yellow solid. ESI-MS: 272.2 [M+H] +

[0299] (2) Synthesis of 2-fluoro-4-(furo[3,2-c]pyridin-4-yl)benzoic acid [126-2] (hereinafter referred to as compound [126-2])

[0300] TIFF0007734129000085.tif2541

[0301] To a solution of compound [126-1] (208 mg) in methanol (7.6 mL), 2 M aqueous sodium hydroxide solution (3.8 mL) was added at room temperature and stirred at 60° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and 2 M hydrochloric acid was added. The resulting solid was collected by filtration, washed with water, and then dried under reduced pressure to obtain the title compound (111 mg) as a gray solid. ESI-MS: 258.2 [M+H] +

[0302] (3) Synthesis of 2-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0126] To a solution of compound [126-2] (51 mg) in DMF (1.0 mL), DIPEA (37 μL) and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (94 mg) were added at room temperature, and the mixture was stirred at room temperature for 5 minutes. 2-(trans-4-aminocyclohexyl)propan-2-ol (41 mg) was added to the reaction mixture at room temperature, and the mixture was stirred at room temperature for 22 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (74 mg) as a yellow solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.31-8.20(m,2H),7.91(dd,J=8.0,1.6Hz,1H),7.84(dd,J=11.4,1.4Hz,1H),7.75(d d,J=5.5,0.9Hz,1H),7.70(t,J=7.5Hz,1H),7.45-7.35(m,1H),4.03(s,1H),3.75-3.61(m,1H),2.00-1.73(m,4H),1.36-0.93(m,11H). ESI-MS: 397.4 [M+H] +

[0303] Example 127 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0127] (hereinafter referred to as compound

[0127] )

[0304] TIFF0007734129000086.tif3662

[0305] (1) Synthesis of 3-hydroxy-6-methyl-3,5-dihydrofuro[3,2-c]pyridin-4(2H)-one [127-1] (hereinafter referred to as compound [127-1])

[0306] TIFF0007734129000087.tif3123

[0307] To a solution of 2,4-dihydroxy-6-methylpyridine (528 mg) in acetone (42 mL), potassium carbonate (1.75 g) was added at room temperature and stirred for 15 minutes. 40% aqueous chloroacetaldehyde (4.15 mL) was added to the reaction mixture at room temperature and stirred for 2 hours. The reaction mixture was concentrated under reduced pressure, and water was added. The resulting solid was collected by filtration and dried under reduced pressure to give the title compound (267 mg) as a brown solid. 1H-NMR(400MHz,DMSO-d6)δ:11.10(br,1H),5.81(s,1H),5.28(d,J=5.9Hz,1H),5.06- 5.01(m,1H),4.44(dd,J=10.5,6.4Hz,1H),4.23(dd,J=10.3,2.1Hz,1H),2.13(s,3H). ESI-MS: 168.2 [M+H] +

[0308] (2) Synthesis of 4-chloro-6-methylfuro[3,2-c]pyridine [127-2] (hereinafter referred to as compound [127-2])

[0309] TIFF0007734129000088.tif2525

[0310] Phosphoryl chloride (4.00 mL) was added to compound [127-1] (266 mg) at room temperature, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was then stirred at 100°C for 3 hours. The reaction mixture was poured into ice-cooled saturated aqueous sodium bicarbonate solution 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 column chromatography to obtain the title compound (152 mg) as a pale yellow solid. 1 H-NMR(400MHz, CDCl3)δ:7.61(d,J=2.3Hz,1H),7.23(s,1H),6.83(dd,J=2.3,0.9Hz,1H),2.63(s,3H). ESI-MS: 168.1 [M+H] +

[0311] (3) Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0127] To a solution of compound [127-2] (37 mg) in ethanol (1.0 mL) / water (1.0 mL), compound [2-1] (78 mg), potassium carbonate (36 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (6.5 mg) were added at room temperature, and the mixture was stirred at 80°C under an argon atmosphere for 3 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (60 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.31(d,J=7.8Hz,1H),8.13(d,J=2.3Hz,1H),8.05(d,J=8.2Hz,2H),7.99(d,J=8.7Hz,2H),7.56(s,1 H),7.28(d,J=1.4Hz,1H),4.04(s,1H),3.80-3.65(m,1H),2.64(s,3H),1.95-1.76(m,4H),1.41-1.26(m,2H),1.23-0.95(m,9H). ESI-MS: 393.4 [M+H] +

[0312] Example 128 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(2-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0128] (hereinafter referred to as compound

[0128] )

[0313] TIFF0007734129000089.tif3060

[0314] To a solution of 4-chloro-2-methylfuro[3,2-c]pyridine (37 mg) in ethanol (1.0 mL) / water (1.0 mL), compound [2-1] (78 mg), potassium carbonate (36 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (6.5 mg) were added at room temperature, and the mixture was stirred at 80°C for 2 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (55 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.50(d,J=5.5Hz,1H),8.30(d,J=8.2Hz,1H),8.05(d,J=8.2Hz,2H),7.99(d,J=8.2Hz,2H),7.60(dd,J=5.5,0.9 Hz,1H),7.04-6.96(m,1H),4.04(s,1H),3.81-3.64(m,1H),2.52(d,J=0.9Hz,3H),1.96-1.75(m,4H),1.40-1.25(m,2H),1.24-0.92(m,9H). ESI-MS: 393.4 [M+H] +

[0315] Example 129 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0129] (hereinafter referred to as compound

[0129] )

[0316] TIFF0007734129000090.tif3062

[0317] (1) Synthesis of 4-chloro-7-methylfuro[3,2-c]pyridine [129-1] (hereinafter referred to as compound [129-1])

[0318] TIFF0007734129000091.tif2026

[0319] To a solution of 7-bromo-4-chlorofuro[3,2-c]pyridine (116 mg) in 1,4-dioxane (2.0 mL), cesium carbonate (163 mg), PdCl(dppf) (36.6 mg), and 2,4,6-trimethylboroxine (70.0 μL) were added at room temperature, and the mixture was stirred at 100°C under an argon atmosphere for 3 hours. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (40.2 mg) as a white solid. 1 H-NMR(400MHz, CDCl3)δ:8.07(s,1H),7.69(d,J=2.3Hz,1H),6.87(d,J=2.3Hz,1H),2.49(s,3H). ESI-MS: 168.2 [M+H] +

[0320] (2) Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0129] To a solution of compound [129-1] (37 mg) in ethanol (1.0 mL) / water (1.0 mL), compound [2-1] (78 mg), potassium carbonate (36 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (6.5 mg) were added at room temperature, and the mixture was stirred at 80°C under an argon atmosphere for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (48 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.42(s,1H),8.30(d,J=8.2Hz,1H),8.23(d,J=2.3Hz,1H),8.05(d,J=8.7Hz,2H),7.99(d,J=8.7Hz,2 H),7.35(d,J=2.3Hz,1H),4.04(s,1H),3.82-3.59(m,1H),2.51(s,3H),2.01-1.64(m,4H),1.45-1.25(m,2H),1.25-0.93(m,9H). ESI-MS: 393.4 [M+H] +

[0321] Example 130 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(3-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0130] (hereinafter referred to as compound

[0130] )

[0322] TIFF0007734129000092.tif3062

[0323] (1) Synthesis of 4-chloro-3-methylfuro[3,2-c]pyridine [130-1] (hereinafter referred to as compound [130-1])

[0324] TIFF0007734129000093.tif2527

[0325] To a solution of 3-bromo-4-chlorofuro[3,2-c]pyridine (41.6 mg) in 1,4-dioxane (3.6 mL), cesium carbonate (70.0 mg), PdCl(dppf)·CHCl(14.6 mg), and 2,4,6-trimethylboroxine (30.0 μL) were added at room temperature and stirred at 100°C for 2 hours under an argon atmosphere. PdCl(dppf)·CHCl(7.3 mg) and 2,4,6-trimethylboroxine (30.0 μL) were added at room temperature and stirred at 100°C for 4 hours under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (14.1 mg) as a yellow solid. ESI-MS: 168.2 [M+H] +

[0326] (2) Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(3-methylfuro[3,2-c]pyridin-4-yl)benzamide

[0130] To a solution of compound [130-1] (20 mg) in ethanol (0.60 mL) / water (0.60 mL), compound [2-1] (45 mg), potassium carbonate (21 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (4.9 mg) were added at room temperature, and the mixture was stirred at 80°C under an argon atmosphere for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (18 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.51(d,J=5.5Hz,1H),8.30(d,J=7.8Hz,1H),8.03-7.91(m,3H),7.75-7. 60(m,3H),4.02(s,1H),3.80-3.66(m,1H),1.96-1.76(m,7H),1.41-1.25(m,2H),1.24-0.96(m,9H). ESI-MS: 393.5 [M+H] +

[0327] Example 131 Synthesis of 3-chloro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0131] (hereinafter referred to as compound

[0131] )

[0328] TIFF0007734129000094.tif3062

[0329] (1) Synthesis of methyl 3-chloro-4-(furo[3,2-c]pyridin-4-yl)benzoate [131-1] (hereinafter referred to as compound [131-1])

[0330] TIFF0007734129000095.tif2541

[0331] To a solution of 4-chlorofuro[3,2-c]pyridine (154 mg) in 1,4-dioxane (4.0 mL) / water (1.0 mL), 2-chloro-4-(methoxycarbonyl)phenylboronic acid (279 mg), potassium phosphate tribasic (425 mg), and PdCl(dppf) (73.2 mg) were added at room temperature, and the mixture was stirred at 100°C under an argon atmosphere for 30 minutes. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography to afford the title compound (103 mg) as a white solid. ESI-MS: 288.2 [M+H] +

[0332] (2) Synthesis of 3-chloro-4-(furo[3,2-c]pyridin-4-yl)benzoic acid [131-2] (hereinafter referred to as compound [131-2])

[0333] TIFF0007734129000096.tif2541

[0334] To a solution of compound [131-1] (31 mg) in methanol (2.2 mL), 2 M aqueous sodium hydroxide solution (1.1 mL) was added at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, and 1 M hydrochloric acid was added. The resulting solid was collected by filtration, washed with water, and then dried under reduced pressure to obtain the title compound (28 mg) as a white solid. ESI-MS: 274.2 [M+H] +

[0335] (3) Synthesis of 3-chloro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0131] To a solution of compound [131-2] (28 mg) in DMF (1.0 mL), DIPEA (19 μL) and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (47 mg) were added at room temperature, and the mixture was stirred at room temperature for 5 minutes. 2-(trans-4-aminocyclohexyl)propan-2-ol (21 mg) was added to the reaction mixture at room temperature, and the mixture was stirred at room temperature for 4 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (31 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.9Hz,1H),8.45(d,J=8.2Hz,1H),8.16(d,J=2.3Hz,1H),8.08(d,J=1.8Hz,1H),7.95(dd,J=7.8,1.8Hz,1H),7 .80-7.74(m,1H),7.63(d,J=7.8Hz,1H),6.85-6.79(m,1H),4.04(s,1H),3 .79-3.66(m,1H),2.03-1.74(m,4H),1.39-1.25(m,2H),1.24-0.94(m,9H). ESI-MS: 413.4 [M+H] +

[0336] Example 132 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-3-methylbenzamide

[0132] (hereinafter referred to as compound

[0132] )

[0337] TIFF0007734129000097.tif3060

[0338] (1) Synthesis of methyl 4-(furo[3,2-c]pyridin-4-yl)-3-methylbenzoate [132-1] (hereinafter referred to as compound [132-1])

[0339] TIFF0007734129000098.tif2032

[0340] To a solution of 4-chlorofuro[3,2-c]pyridine (154 mg) in methanol (2.5 mL) / water (2.5 mL), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (359 mg), potassium carbonate (180 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (26.0 mg) were added at room temperature, and the mixture was stirred at 80°C for 1 hour under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (272 mg) as a yellow solid. ESI-MS: 268.1 [M+H] +

[0341] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-3-methylbenzamide

[0132] The title compound was synthesized from the compound [132-1] according to the methods of steps (2) and (3) of Example 131. 1 H-NMR(400MHz,DMSO-d6)δ:8.55(d,J=5.5Hz,1H),8.25(d,J=7.8Hz,1H),8.14 (d,J=2.3Hz,1H),7.84(s,1H),7.78(dd,J=7.8,1.4Hz,1H),7.71(dd,J=5.9,0 .9Hz,1H),7.45(d,J=7.8Hz,1H),6.83-6.77(m,1H),4.04(s,1H),3.79-3.65( m,1H),2.27(s,3H),1.96-1.77(m,4H),1.40-1.24(m,2H),1.23-0.97(m,9H). ESI-MS: 393.4 [M+H] +

[0342] Example 133 Synthesis of 3-cyano-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0133] (hereinafter referred to as compound

[0133] )

[0343] TIFF0007734129000099.tif3062

[0344] (1) Synthesis of methyl 3-cyano-4-(furo[3,2-c]pyridin-4-yl)benzoate [133-1] (hereinafter referred to as compound [133-1])

[0345] TIFF0007734129000100.tif2541

[0346] To a solution of 4-chlorofuro[3,2-c]pyridine (41 mg) in 1,2-dimethoxyethane (2.6 mL), methyl 3-cyano-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (83 mg), cesium fluoride (88 mg), and bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (9.3 mg) were added at room temperature, and the mixture was stirred at 100°C for 1 hour under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (34 mg) as a pale yellow solid. ESI-MS: 279.3 [M+H] +

[0347] (2) Synthesis of 3-cyano-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0133] The title compound was synthesized from the compound [133-1] according to the methods of steps (2) and (3) of Example 131. 1H-NMR(400MHz,DMSO-d6)δ:8.64(d,J=5.5Hz,1H),8.54(d,J=7.8Hz,1H),8.47(d,J=1.8Hz,1H),8.32-8.22(m,2H),7.98(d,J=8.2Hz,1H) ,7.84(d,J=5.5Hz,1H),7.14(d,J=1.8Hz,1H),4.05(s,1H),3.80-3.66(m,1H),2.03-1.76(m,4H),1.39-1.25(m,2H),1.24-0.93(m,9H). ESI-MS: 404.4 [M+H] +

[0348] Example 134 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-3-hydroxy-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0134] (hereinafter referred to as compound

[0134] )

[0349] TIFF0007734129000101.tif3062

[0350] (1) Synthesis of methyl 4-(furo[3,2-c]pyridin-4-yl)-3-methoxybenzoate [134-1] (hereinafter referred to as compound [134-1])

[0351] TIFF0007734129000102.tif2541

[0352] To a solution of 4-chlorofuro[3,2-c]pyridine (76.8 mg) in methanol (1.25 mL) / water (1.25 mL), 2-methoxy-4-(methoxycarbonyl)phenylboronic acid (137 mg), potassium carbonate (89.8 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (13.0 mg) were added at room temperature, and the mixture was stirred at 80°C for 30 minutes under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to afford the title compound (117 mg) as a pale yellow solid. ESI-MS: 284.3 [M+H] +

[0353] (2) Synthesis of methyl 4-(furo[3,2-c]pyridin-4-yl)-3-hydroxybenzoate [134-2] (hereinafter referred to as compound [134-2])

[0354] TIFF0007734129000103.tif2541

[0355] To a solution of compound [134-1] (56 mg) in dichloromethane (1.0 mL), a 1 M solution of boron tribromide in dichloromethane (989 μL) was added at 0°C under an argon atmosphere, and the mixture was stirred at 0°C for 3 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (10 mg) as a yellow solid. ESI-MS: 270.3 [M+H] +

[0356] (3) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-3-hydroxy-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0134] The title compound was synthesized from the compound [134-2] according to the methods of steps (2) and (3) of Example 131. 1 H-NMR(400MHz,DMSO-d6)δ:8.57(d,J=5.9Hz,1H),8.33(d,J=2.3Hz,1H),8.27(d,J=8.2Hz,1H),8.12(d,J=8.2Hz,1H),7.86 -7.80(m,1H),7.64-7.55(m,1H),7.49-7.40(m,2H),4.03(s,1H),3.77-3.62(m,1H),1.94-1.76(m,4H),1.39-0.98(m,11H). ESI-MS: 395.4 [M+H] +

[0357] Example 135 Synthesis of 4-[7-(hydroxymethyl)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0135] (hereinafter referred to as compound

[0135] )

[0358] TIFF0007734129000104.tif3069

[0359] (1) Synthesis of 4-chlorofuro[3,2-c]pyridine-7-carbaldehyde [135-1] (hereinafter referred to as compound [135-1])

[0360] TIFF0007734129000105.tif2528

[0361] To a solution of 7-bromo-4-chlorofuro[3,2-c]pyridine (233 mg) in THF (5.0 mL) was added a 1.3 M solution of isopropylmagnesium chloride-lithium chloride complex (1.15 mL) in THF at room temperature under an argon atmosphere, and the mixture was stirred at room temperature for 20 minutes. Next, N-formylpiperidine (222 μL) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. After adding 1 M hydrochloric acid to the reaction mixture, saturated aqueous sodium bicarbonate solution was added, and the mixture was 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 column chromatography to give the title compound (155 mg) as a white solid. 1 H-NMR(400MHz, CDCl3)δ:10.40(s,1H),8.75(s,1H),7.87(d,J=2.3Hz,1H),7.01(d,J=1.8Hz,1H). ESI-MS: 182.2 [M+H] +

[0362] (2) Synthesis of 4-(7-formylfuro[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide [135-2] (hereinafter referred to as compound [135-2])

[0363] TIFF0007734129000106.tif3663

[0364] To a solution of compound [135-1] (72.6 mg) in 1,4-dioxane (3.2 mL) / water (0.8 mL), compound [2-1] (155 mg), potassium phosphate tribasic (170 mg), and PdCl(dppf)·CHCl (16.3 mg) were added at room temperature, and the mixture was stirred at 100°C for 15 minutes under an argon atmosphere. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (139 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:10.37(s,1H),9.08(s,1H),8.41(d,J=2.3Hz,1H),8.37(d,J=7.8Hz,1H),8.16(d,J=8.7Hz,2H),8.04( d,J=8.7Hz,2H),7.50(d,J=2.3Hz,1H),4.04(s,1H),3.80-3.66(m,1H),1.97-1.71(m,4H),1.42-1.26(m,2H),1.24-0.94(m,9H). ESI-MS: 407.4 [M+H] +

[0365] (3) Synthesis of 4-[7-(hydroxymethyl)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0135] To a solution of compound [135-2] (20 mg) in methanol (1.0 mL), sodium borohydride (5.7 mg) was added at room temperature and stirred for 20 minutes. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (17 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.55(s,1H),8.31(d,J=8.2Hz,1H),8.24(d,J=2.3Hz,1H),8.07(d,J=8.7Hz,2H),8.00(d,J=8.2Hz,2H),7.36(d, J=2.3Hz,1H),5.46(br,1H),4.86(d,J=3.7Hz,2H),4.04(s,1H),3.79-3.65(m,1H),1.96-1.75(m,4H),1.43-1.24(m,2H),1.24-0.96(m,9H). ESI-MS: 409.4 [M+H] +

[0366] Example 136 Synthesis of 4-(7-fluorofuro[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0136] (hereinafter referred to as compound

[0136] )

[0367] TIFF0007734129000107.tif3159

[0368] (1) Synthesis of 4-chloro-7-fluorofuro[3,2-c]pyridine [136-1] (hereinafter referred to as compound [136-1])

[0369] TIFF0007734129000108.tif2023

[0370] To a solution of 7-bromo-4-chlorofuro[3,2-c]pyridine (47 mg) in THF (0.50 mL) was added a 1.3 M solution of isopropylmagnesium chloride-lithium chloride complex in THF (0.23 mL) at 0°C under an argon atmosphere, and the mixture was stirred at room temperature for 40 minutes. The reaction mixture was concentrated under reduced pressure, and dichloromethane (0.50 mL) was added at room temperature, followed by cooling to 0°C. Next, a solution of N-fluorobenzenesulfonimide (95 mg) in dichloromethane (0.50 mL) was added at 0°C, and the mixture was stirred at room temperature for 2 hours. Chloroform was added to the reaction mixture, and the mixture was purified by silica gel column chromatography to obtain the title compound (5.7 mg) as a white solid. 1 H-NMR(400MHz, CDCl3)δ:8.18(d,J=2.3Hz,1H),7.76(d,J=2.3Hz,1H),6.94(dd,J=2.5,2.5Hz,1H).

[0371] (2) Synthesis of 4-(7-fluorofuro[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0136] To a solution of compound [136-1] (5.5 mg) in ethanol (0.50 mL) / water (0.50 mL), compound [2-1] (12 mg), potassium carbonate (5.8 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (1.0 mg) were added at room temperature, and the mixture was stirred at 80°C under an argon atmosphere for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (7.4 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.64(d,J=1.8Hz,1H),8.36(d,J=2.3Hz,1H),8.32(d,J=8.2Hz,1H),8.09-7.95(m,4H),7 .47(dd,J=2.5,2.5Hz,1H),4.04(s,1H),3.79-3.66(m,1H),1.96-1.76(m,4H),1.43-1.25(m,2H),1.24-0.92(m,9H). ESI-MS: 397.4 [M+H] +

[0372] Example 137 Synthesis of N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-vinylfuro[3,2-c]pyridin-4-yl)benzamide

[0137] (hereinafter referred to as compound

[0137] )

[0373] TIFF0007734129000109.tif3066

[0374] To a solution of methyltriphenylphosphonium bromide (237 mg) in THF (2.7 mL), potassium tert-butoxide (74.5 mg) was added at room temperature and stirred for 5 minutes. Next, a solution of compound [135-2] (54.0 mg) in THF (1.8 mL) was added to the reaction mixture at room temperature, and the mixture was stirred for 3 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (29.1 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.65(s,1H),8.36-8.27(m,2H),8.08(d,J=8.7Hz ,2H),8.00(d,J=8.2Hz,2H),7.40(d,J=2.3Hz,1H),7.00(dd,J=17.8,11.9Hz, 1H),6.38(dd,J=17.8,0.9Hz,1H),5.70(dd,J=11.4,0.9Hz,1H),4.04(s,1H) ,3.79-3.66(m,1H),1.95-1.76(m,4H),1.39-1.26(m,2H),1.23-0.99(m,9H). ESI-MS: 405.3 [M+H] +

[0375] Example 138 Synthesis of 4-(7-ethylfuro[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0138] (hereinafter referred to as compound

[0138] )

[0376] TIFF0007734129000110.tif2451

[0377] To a solution of compound

[0137] (15 mg) in methanol (1.0 mL), 5% palladium on activated carbon (15 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 1 hour. Insoluble matter was filtered off, and the mixture was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography to give the title compound (7.2 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.44(s,1H),8.30(d,J=7.8Hz,1H),8.23(d,J=2.3Hz,1H),8.05(d,J=8.2Hz,2H),7.99(d,J=8.7Hz,2H),7 .34(d,J=2.3Hz,1H),4.04(s,1H),3.83-3.65(m,1H),2.94(q,J=7.6Hz,2H),1.96-1.76(m,4H),1.42-1.25(m,5H),1.24-0.90(m,9H). ESI-MS: 407.4 [M+H] +

[0378] Example 139 Synthesis of 4-(7-cyanofuro[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0139] (hereinafter referred to as compound

[0139] )

[0379] TIFF0007734129000111.tif3162

[0380] (1) Synthesis of 4-chlorofuro[3,2-c]pyridine-7-carbonitrile [139-1] (hereinafter referred to as compound [139-1])

[0381] TIFF0007734129000112.tif2026

[0382] To a solution of [135-1] (54.5 mg) in DMF (1.0 mL), hydroxylamine hydrochloride (31.3 mg) and triethylamine (62.7 μL) were added at room temperature, followed by stirring at room temperature for 5 minutes. Next, a 1.7 M solution of propylphosphonic anhydride in ethyl acetate (265 μL) was added at room temperature, followed by stirring at 100°C for 7 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, followed by extraction 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 column chromatography to yield the title compound (45.9 mg) as a white solid. ESI-MS: 179.2 [M+H] +

[0383] (2) Synthesis of 4-(7-cyanofuro[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0139] To a solution of compound [139-1] (44.6 mg) in ethanol (1.25 mL) / water (1.25 mL), compound [2-1] (96.8 mg), potassium carbonate (44.9 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (8.1 mg) were added at room temperature, and the mixture was stirred at 80°C under an argon atmosphere for 2 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (60.4 mg) as a white solid. ESI-MS: 404.3 [M+H] +

[0384] Example 140 Synthesis of 4-(4-{[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]carbamoyl}phenyl)furo[3,2-c]pyridine-7-carboxamide

[0140] (hereinafter referred to as compound

[0140] )

[0385] TIFF0007734129000113.tif3661

[0386] To a solution of compound

[0139] (19.6 mg) in tert-butanol (972 μL) was added potassium tert-butoxide (81.8 mg) at room temperature, and the mixture was stirred at 40° C. under an argon atmosphere for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure, and ethanol and water were added to the resulting residue. The solid was collected by filtration, washed with water, and then dried under reduced pressure to obtain the title compound (17.1 mg) as a white solid. ESI-MS: 422.3 [M+H] +

[0387] Example 141 Synthesis of 4-[7-(1-hydroxyethyl)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0141] (hereinafter referred to as compound

[0141] )

[0388] TIFF0007734129000114.tif3670

[0389] (1) Synthesis of 1-(4-chlorofuro[3,2-c]pyridin-7-yl)ethan-1-ol [141-1] (hereinafter referred to as compound [141-1])

[0390] TIFF0007734129000115.tif2535

[0391] To a solution of compound [135-1] (10.7 mg) in THF (1.2 mL), a 3M THF solution of methylmagnesium chloride (39 μL) was added at 0° C. under an argon atmosphere, and the mixture was stirred at 0° C. for 10 minutes. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (9.4 mg) as a colorless oil. ESI-MS: 198.2 [M+H] +

[0392] (2) Synthesis of 4-[7-(1-hydroxyethyl)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide

[0141] To a solution of compound [141-1] (9.4 mg) in ethanol (0.48 mL) / water (0.48 mL), compound [2-1] (18 mg), potassium carbonate (8.6 mg), and [1,3-bis(2,6-diisopropylphenyl)-4,5-dihydroimidazol-2-ylidene]chloro[3-phenylallyl]palladium(II) (1.6 mg) were added at room temperature, and the mixture was stirred at 80°C under an argon atmosphere for 3 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (16 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(s,1H),8.30(d,J=8.2Hz,1H),8.23(d,J=2. 3Hz,1H),8.05(d,J=8.7Hz,2H),7.99(d,J=8.7Hz,2H),7.34(d,J=2.3Hz,1H), 5.54(d,J=4.6Hz,1H),5.31-5.19(m,1H),4.03(s,1H),3.80-3.65(m,1H),1. 96-1.77(m,4H),1.54(d,J=6.4Hz,3H),1.40-1.25(m,2H),1.24-0.92(m,9H). ESI-MS: 423.3 [M+H] +

[0393] Example 142 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(piperidin-4-yl)benzamide

[0142] (hereinafter referred to as compound

[0142] )

[0394] TIFF0007734129000116.tif2551

[0395] To a solution of compound [99-1] (500 mg) in DMF (7.00 mL), DIPEA (392 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (986 mg), and tert-butyl 4-aminopiperidine-1-carboxylate (461 mg) were added at room temperature, and the mixture was stirred at room temperature for 16 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the resulting residue in dichloromethane (20.0 mL), trifluoroacetic acid (14.0 mL) was added at room temperature, and the mixture was stirred at room temperature for 30 minutes. A 5 M aqueous solution of sodium hydroxide was added to the reaction mixture at 0° C., and the mixture was 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 column chromatography to give the title compound (420 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(dd,J=5.7,2.1Hz,1H),8.37(d,J=7.8Hz,1H),8.24-8.23(m,1H),8.12-8.05(m,2H),8.04-7.98(m,2H),7.72(d ,J=5.9Hz,1H),7.37-7.35(m,1H),3.88-3.80(m,1H),3.31-3.30(m,2H) ,2.97-2.94(m,2H),1.76-1.72(m,2H),2.05(br,1H),1.47-1.39(m,2H). ESI-MS: 322.4 [M+H] +

[0396] Example 143 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)piperidin-4-yl]benzamide

[0143] (hereinafter referred to as compound

[0143] )

[0397] TIFF0007734129000117.tif3156

[0398] To a solution of compound

[0142] (20.0 mg) in NMP (300 μL), potassium carbonate (77.0 mg) and 2-chloropyrimidine (32.0 mg) were added at room temperature, and the mixture was stirred at 140° C. for 4 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (14.0 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.5Hz,1H),8.41(d,J=7.3Hz,1H),8.36(d,J =5.0Hz,2H),8.24(d,J=2.3Hz,1H),8.09(d,J=8.2Hz,2H),8.01(d,J=8.2Hz,2H),7. 72(dd,J=5.5,0.9Hz,1H),7.36(d,J=2.3Hz,1H),6.61(t,J=4.8Hz,1H),4.67-4.64( m,2H),4.19-4.11(m,1H),3.06-3.00(m,2H),1.91-1.87(m,2H),1.55-1.46(m,2H). ESI-MS: 400.4 [M+H] +

[0399] Examples 144 to 170 The compounds of Examples 144 to 170 shown in the table below were synthesized according to the method shown in Example 143. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0400] [Table 4-1]

[0401] [Table 4-2]

[0402] [Table 4-3]

[0403] [Table 4-4]

[0404] [Table 4-5]

[0405] [Table 4-6]

[0406] Example 171 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-4-yl)piperidin-4-yl]benzamide

[0171] (hereinafter referred to as compound

[0171] )

[0407] TIFF0007734129000124.tif2547

[0408] To a solution of compound

[0146] (20 mg) in ethanol (0.50 mL), 10% palladium on activated carbon (2.0 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 23 hours. The reaction mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (2.1 mg) as a white solid. ESI-MS: 400.5 [M+H] +

[0409] Example 172 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(6-oxo-1,6-dihydropyridin-2-yl)piperidin-4-yl]benzamide

[0172] (hereinafter referred to as compound

[0172] )

[0410] TIFF0007734129000125.tif3162

[0411] To a solution of compound

[0147] (10 mg) in 1,4-dioxane (0.20 mL), 5 M hydrochloric acid (0.20 mL) was added at room temperature, and the mixture was stirred at room temperature for 23 hours. A 5 M aqueous solution of sodium hydroxide was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (2.1 mg) as a white solid. 1 H-NMR(400MHz,CD3OD)δ:8.53(d,J=5.5Hz,1H),8.01-7.99(m,5H),7.63(d,J=5.9Hz,1H),7.44(t,J=8.2Hz,1H),7.19-7.18 (m,1H),5.90-5.88(m,2H),4.18-4.14(m,1H),3.92-3.89(m,2H),3.06-3.01(m,2H),2.18-2.06(m,2H),1.79-1.74(m,2H). ESI-MS: 415.4 [M+H] +

[0412] Example 173 Synthesis of N-[1-(5-cyanopyrimidin-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0173] (hereinafter referred to as compound

[0173] )

[0413] TIFF0007734129000126.tif3061

[0414] To a solution of compound

[0154] (13.4 mg) in DMF (0.60 mL), zinc cyanide (6.6 mg) and Pd(PPh3)4 (6.5 mg) were added at room temperature, and the mixture was stirred at 120 °C for 30 minutes using a microwave reactor under an argon atmosphere. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (5.6 mg) as a white solid. ESI-MS: 425.4 [M+H] +

[0415] Example 174 Synthesis of 2-{4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]piperidin-1-yl}pyrimidine-5-carboxamide

[0174] (hereinafter referred to as compound

[0174] )

[0416] TIFF0007734129000127.tif3667

[0417] To a solution of compound

[0173] (14.6 mg) in tert-butanol (0.60 mL), potassium tert-butoxide (93.0 mg) was added at room temperature and stirred at 80°C for 2 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (5.5 mg) as a white solid. ESI-MS: 443.4 [M+H] +

[0418] Example 175 Synthesis of 2-{4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]piperidin-1-yl}pyrimidine-4-carboxamide

[0175] (hereinafter referred to as compound

[0175] )

[0419] TIFF0007734129000128.tif3069

[0420] To a solution of compound

[0164] (10.6 mg) in tert-butanol (0.50 mL), potassium tert-butoxide (67.0 mg) was added at room temperature and stirred at 80°C for 3 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (3.8 mg) as a white solid. ESI-MS: 443.4 [M+H] +

[0421] Example 176 Synthesis of 4-{4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]piperidin-1-yl}picolinamide

[0176] (hereinafter referred to as compound

[0176] )

[0422] TIFF0007734129000129.tif3169

[0423] To a solution of compound

[0166] (7.8 mg) in tert-butanol (0.40 mL), potassium tert-butoxide (50 mg) was added at room temperature and stirred at 80°C for 3 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (5.4 mg) as a white solid. ESI-MS: 442.4 [M+H] +

[0424] Example 177 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(5-sulfamoylpyrimidin-2-yl)piperidin-4-yl]benzamide

[0177] (hereinafter referred to as compound

[0177] )

[0425] TIFF0007734129000130.tif3672

[0426] (1) Synthesis of N-(1-{5-[N-(tert-butyl)sulfamoyl]pyrimidin-2-yl}piperidin-4-yl)-4-(furo[3,2-c]pyridin-4-yl)benzamide [177-1] (hereinafter referred to as compound [177-1])

[0427] TIFF0007734129000131.tif3672

[0428] To a solution of 2-chloropyrimidine-5-sulfonyl chloride (100 mg) in THF (1.50 mL) was added tert-butylamine (60.0 μL) at 0° C., followed by stirring at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. To a solution of the resulting residue in DMSO (150 μL), potassium carbonate (10.0 mg) and compound

[0142] (10.0 mg) were added at room temperature, followed by stirring at 140° C. for 4 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (9.6 mg) as a white solid. ESI-MS: 535.3 [M+H] +

[0429] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(5-sulfamoylpyrimidin-2-yl)piperidin-4-yl]benzamide

[0177] To a solution of compound [177-1] (9.60 mg) in ethyl acetate (200 μL), trifluoroacetic acid (200 μL) was added at room temperature, and the mixture was stirred at 80° C. for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (0.73 mg) as a white solid. ESI-MS: 479.4 [M+H] +

[0430] Example 178 Synthesis of N-{1-[4-(azetidin-1-yl)pyrimidin-2-yl]piperidin-4-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0178] (hereinafter referred to as compound

[0178] )

[0431] TIFF0007734129000132.tif4156

[0432] (1) Synthesis of 4-(azetidin-1-yl)-2-chloropyrimidine [178-1] (hereinafter referred to as compound [178-1])

[0433] TIFF0007734129000133.tif2519

[0434] Cesium carbonate (437 mg) and azetidine hydrochloride (69.0 mg) were added to a solution of 2,4-dichloropyrimidine (100 mg) in THF (1.00 mL) at room temperature, and the mixture was stirred at 60°C for 19 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (15.5 mg) as a white solid. ESI-MS: 170.2 [M+H] +

[0435] (2) Synthesis of N-{1-[4-(azetidin-1-yl)pyrimidin-2-yl]piperidin-4-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0178] To a solution of compound

[0142] (27.0 mg) in NMP (300 μL), cesium carbonate (59.0 mg) and compound [178-1] (15.5 mg) were added at room temperature, and the mixture was stirred at 140° C. for 4 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (12.2 mg) as a yellow solid. ESI-MS: 455.4 [M+H] +

[0436] Example 179 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]benzamide

[0179] (hereinafter referred to as compound

[0179] )

[0437] TIFF0007734129000134.tif3162

[0438] (1) Synthesis of 2-chloropyrimidin-4(3H)-one [179-1] (hereinafter referred to as compound [179-1])

[0439] TIFF0007734129000135.tif2018

[0440] 2,4-Dichloropyrimidine (1.00 g) was added to 5 M aqueous sodium hydroxide solution (2.68 mL) at room temperature and stirred at 80°C for 4 hours. 5 M hydrochloric acid was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (780 mg) as a yellow solid. ESI-MS: 131.1 [M+H] +

[0441] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]benzamide

[0179] To a solution of compound

[0142] (20 mg) in NMP (0.30 mL), potassium carbonate (56 mg) and compound [179-1] (23 mg) were added at room temperature, and the mixture was stirred at 140°C for 17 hours. 1M hydrochloric acid was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (7.5 mg) as a yellow solid. ESI-MS: 416.4 [M+H] +

[0442] Example 180 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]benzamide

[0180] (hereinafter referred to as compound

[0180] )

[0443] TIFF0007734129000136.tif2560

[0444] To a solution of compound

[0142] (10 mg) in 1,4-dioxane (0.30 mL), DIPEA (16 μL) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (5.4 μL) were added at room temperature, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography to give the title compound (8.5 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.38(d,J=7.8Hz,1H),8.24 (d,J=2.3Hz,1H),8.14-8.06(m,2H),8.01(dd,J=6.6,2.1Hz,2H),7.72(dd,J= 5.5,0.9Hz,1H),7.37-7.36(m,1H),3.84-3.77(m,1H),3.17(q,J=10.2Hz,2H) ,2.96-2.93(m,2H),2.47-2.39(m,2H),1.84-1.78(m,2H),1.66-1.56(m,2H). ESI-MS: 404.4 [M+H] +

[0445] Example 181 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]benzamide

[0181] (hereinafter referred to as compound

[0181] )

[0446] TIFF0007734129000137.tif3665

[0447] (1) Synthesis of 2-chloro-6-methylpyrimidin-4(3H)-one trifluoroacetate [181-1] (hereinafter referred to as compound [181-1])

[0448] TIFF0007734129000138.tif2045

[0449] To 2,4-dichloro-6-methylpyrimidine (155 mg), a 5 M aqueous sodium hydroxide solution (536 μL) was added at room temperature, followed by stirring for 4 hours at 80° C. The reaction mixture was purified by reverse-phase silica gel column chromatography to obtain the title compound (89.3 mg) as a yellow solid. ESI-MS: 145.3 [M+H] +

[0450] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(4-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]benzamide

[0181] To a solution of compound

[0142] (20 mg) in NMP (0.3 mL), potassium carbonate (25 mg) and compound [181-1] (18 mg) were added at room temperature, and the mixture was stirred at 140°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (7.8 mg) as a white solid. ESI-MS: 430.4 [M+H] +

[0451] Example 182 Synthesis of N-[1-(5-bromo-6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0182] (hereinafter referred to as compound

[0182] )

[0452] TIFF0007734129000139.tif3060

[0453] (1) Synthesis of 5-bromo-2-chloropyrimidin-4(3H)-one [182-1] (hereinafter referred to as compound [182-1])

[0454] TIFF0007734129000140.tif2025

[0455] 5-Bromo-2,4-dichloropyrimidine (5.0 g) was added to 5 M aqueous sodium hydroxide solution (8.8 mL) at room temperature and stirred at 80°C for 3 hours. 1 M hydrochloric acid was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was suspended in chloroform / n-hexane, and the solid was collected by filtration to give the title compound (2.2 g) as a yellow solid. ESI-MS: 209.1 [M+H] +

[0456] (2) Synthesis of N-[1-(5-bromo-6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0182] To a solution of compound

[0142] (20 mg) in NMP (0.30 mL), potassium carbonate (25 mg) and compound [182-1] (18 mg) were added at room temperature, and the mixture was stirred at 140°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (7.8 mg) as a white solid. ESI-MS: 494.4 [M+H] +

[0457] Example 183 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]benzamide

[0183] (hereinafter referred to as compound

[0183] )

[0458] TIFF0007734129000141.tif3162

[0459] (1) Synthesis of 2-chloro-3-methylpyrimidin-4(3H)-one [183-1] (hereinafter referred to as compound [183-1])

[0460] TIFF0007734129000142.tif2018

[0461] To a solution of compound [179-1] (680 mg) in 1,4-dioxane (11.0 mL), potassium tert-butoxide (1.14 g) was added at room temperature and stirred for 10 minutes. Iodomethane (2.06 mL) was added to the reaction mixture at room temperature and stirred at 80°C for 6 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (32.0 mg) as a white solid. 1 H-NMR(400MHz, CDCl3)δ:7.69(d,J=6.9Hz,1H),6.37(d,J=6.4Hz,1H),3.64(s,3H).

[0462] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)piperidin-4-yl]benzamide

[0183] To a solution of compound

[0142] (59 mg) in NMP (0.6 mL), potassium carbonate (76 mg) and compound [183-1] (32 mg) were added at room temperature, and the mixture was stirred at 120°C for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (62 mg) as a yellow solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.9Hz,1H),8.50(d,J=7.3Hz,1H),8.24 (d,J=2.3Hz,1H),8.10(d,J=8.7Hz,2H),8.04(d,J=8.7Hz,2H),7.73(d,J=6.4H z,2H),7.37-7.36(m,1H),6.00(d,J=6.4Hz,1H),4.15-3.99(m,1H),3.61-3.58 (m,2H),3.37(s,3H),2.99-2.93(m,2H),1.93-1.91(m,2H),1.79-1.70(m,2H). ESI-MS: 430.4 [M+H] +

[0463] Example 184 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-6-oxo-1,6-dihydropyridin-2-yl)piperidin-4-yl]benzamide Synthesis of

[0184] (hereinafter referred to as compound

[0184] )

[0464] TIFF0007734129000143.tif3162

[0465] To a solution of 2,6-difluoropyridine (1.00 g) in tert-butanol (29.0 mL), potassium tert-butoxide (2.90 g) was added at room temperature and stirred for 2 hours. Formic acid (992 μL) was added to the reaction mixture at room temperature and stirred for 20 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product (340 mg). To a solution of the obtained crude product (100 mg) in 1,4-dioxane (3.00 mL), potassium tert-butoxide (300 mg) was added at room temperature and stirred for 20 minutes. Iodomethane (550 μL) was added to the reaction mixture at room temperature and stirred at 80°C for 1 hour. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the resulting residue in NMP (0.30 mL), potassium carbonate (25.0 mg) and compound

[0142] (20.0 mg) were added at room temperature, and the mixture was stirred at 120°C for 3 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (3.2 mg) as a brown solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.3Hz,1H),8.51(d,J=7.8Hz,1H),8.24(d,J=2.3H z,1H),8.15-8.08(m,2H),8.04(dd,J=6.4,1.8Hz,2H),7.73(dd,J=5.9,0.9Hz,1H),7.42- 7.30(m,2H),6.09(dd,J=9.1,0.9Hz,1H),5.86(dd,J=7.3,0.9Hz,1H),4.04-4.00(m,1H), 3.40(s,3H),3.21-3.19(m,2H),2.78-2.72(m,2H),1.98-1.94(m,2H),1.85-1.68(m,2H). ESI-MS: 429.4 [M+H] +

[0466] Example 185 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(2-hydroxypropan-2-yl)pyrimidin-2-yl]piperidin-4-yl}benzamide

[0185] (hereinafter referred to as compound

[0185] )

[0467] TIFF0007734129000144.tif3672

[0468] (1) Synthesis of 2-(2-chloropyrimidin-5-yl)propan-2-ol [185-1] (hereinafter referred to as compound [185-1])

[0469] TIFF0007734129000145.tif2036

[0470] To a solution of ethyl 2-chloropyrimidine-5-carboxylate (100 mg) in THF (1.78 mL), a 3 M solution of methylmagnesium bromide in diethyl ether (533 μL) was added at 0°C, and the mixture was stirred at 40°C for 2 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (25.4 mg) as a white solid. ESI-MS: 173.2 [M+H] +

[0471] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(2-hydroxypropan-2-yl)pyrimidin-2-yl]piperidin-4-yl}benzamide

[0185] To a solution of compound

[0142] (19 mg) in NMP (0.30 mL), potassium carbonate (25 mg) and compound [185-1] (10 mg) were added at room temperature, and the mixture was stirred at 120°C for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (8.2 mg) as a white solid. ESI-MS: 458.5 [M+H] +

[0472] Example 186 Synthesis of N-(1-acetylpiperidin-4-yl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0186] (hereinafter referred to as compound

[0186] )

[0473] TIFF0007734129000146.tif3054

[0474] To a solution of compound

[0142] (20 mg) in NMP (0.30 mL), cesium carbonate (60 mg) and acetyl chloride (3.9 μL) were added at room temperature, and the mixture was stirred at 120° C. for 14 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (10 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(dd,J=5.5,1.4Hz,1H),8.50-8.38(m,1H),8.24( d,J=2.3Hz,1H),8.10(d,J=6.9Hz,2H),8.06-7.98(m,2H),7.73(d,J=5.5Hz,1H),7 .37-7.35(m,1H),4.34-4.31(m,1H),4.20-3.97(m,1H),3.84-3.80(m,1H),3.16-3 .09(m,1H),2.80-2.61(m,1H),2.02(s,3H),1.85-1.80(m,2H),1.58-1.32(m,2H). ESI-MS: 364.3 [M+H] +

[0475] Example 187 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{1-[4-(hydroxymethyl)pyrimidin-2-yl]piperidin-4-yl}benzamide

[0187] (hereinafter referred to as compound

[0187] )

[0476] TIFF0007734129000147.tif3168

[0477] To a solution of compound

[0167] (15 mg) in THF (0.40 mL) was added sodium borohydride (12 mg) at 0°C, and the mixture was stirred at room temperature for 17 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (10 mg) as a white solid. ESI-MS: 430.3 [M+H] +

[0478] Example 188 Synthesis of N-{1-[5-(N-acetylacetamido)pyrimidin-2-yl]piperidin-4-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0188] (hereinafter referred to as compound

[0188] )

[0479] TIFF0007734129000148.tif4172

[0480] (1) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(5-nitropyrimidin-2-yl)piperidin-4-yl]benzamide [188-1] (hereinafter referred to as compound [188-1])

[0481] TIFF0007734129000149.tif3674

[0482] To a solution of compound

[0142] (40.0 mg) in NMP (370 μL), potassium carbonate (77.0 mg) and 2-chloro-5-nitropyrimidine (27.0 mg) were added at room temperature, and the mixture was stirred at 120° C. for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (28.6 mg) as a yellow solid. ESI-MS: 445.3 [M+H]+

[0483] (2) Synthesis of N-{1-[5-(N-acetylacetamido)pyrimidin-2-yl]piperidin-4-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0188] To a solution of compound [188-1] (24 mg) in ethanol (0.40 mL) / water (0.40 mL), iron (15 mg) and ammonium chloride (29 mg) were added at room temperature, and the mixture was stirred at 80°C for 4 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product (51 mg). To a solution of the obtained crude product (20 mg) in dichloromethane (0.50 mL), triethylamine (20 μL) and acetyl chloride (17 μL) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (2.1 mg) as a white solid. ESI-MS: 499.3 [M+H] +

[0484] Example 189 Synthesis of N-[1-(5-acetamidopyrimidin-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0189] (hereinafter referred to as compound

[0189] )

[0485] TIFF0007734129000150.tif3670

[0486] To a solution of compound [188-1] (24 mg) in ethanol (0.40 mL) / water (0.40 mL), iron (15 mg) and ammonium chloride (29 mg) were added at room temperature, and the mixture was stirred at 80°C for 4 hours. The reaction mixture was filtered and concentrated under reduced pressure to obtain a crude product (51 mg). To a solution of the obtained crude product (30 mg) in dichloromethane (0.30 mL), triethylamine (30 μL) and acetyl chloride (6.7 μL) were added at room temperature, and the mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (6.4 mg) as a white solid. ESI-MS: 457.3 [M+H] +

[0487] Example 190 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyridazin-3-yl)piperidin-4-yl]benzamide

[0190] (hereinafter referred to as compound

[0190] )

[0488] TIFF0007734129000151.tif3157

[0489] To a solution of compound [99-1] (20 mg) in dichloromethane (0.30 mL), 4-dimethylaminopyridine (11 mg), EDC (17 mg), and 1-(pyridazin-3-yl)piperidin-4-amine (16 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (12 mg) as a yellow solid. 1H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.5Hz,1H),8.53-8.52(m,1H),8.43(d,J=8.2Hz,1H),8.24(d,J=2.3Hz,1H),8.12-8.06(m,2H),8.05-7.99(m, 2H),7.72(dd,J=5.5,0.9Hz,1H),7.38-7.29(m,3H),4.42-4.39(m,2H),4. 18-4.15(m,1H),3.09-3.04(m,2H),1.92-1.90(m,2H),1.64-1.55(m,2H). ESI-MS: 400.4 [M+H] +

[0490] Example 191 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)pyrrolidin-3-yl]benzamide

[0191] (hereinafter referred to as compound

[0191] )

[0491] TIFF0007734129000152.tif3651

[0492] (1) Synthesis of (S)-tert-butyl 3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]pyrrolidine-1-carboxylate [191-1] (hereinafter referred to as compound [191-1])

[0493] TIFF0007734129000153.tif3051

[0494] To a solution of compound [99-1] (520 mg) in dichloromethane (4.00 mL), 4-dimethylaminopyridine (279 mg), EDC (437 mg), and (S)-3-aminopyrrolidine-1-carboxylate tert-butyl (432 μL) were added at room temperature, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (810 mg) as a yellow oil. 1 H-NMR(400MHz,DMSO-d6)δ:8.67-8.65(m,1H),8.60-8.58(m,1H),8.25-8.23(m,1H),8.10(d,J=4.6Hz,2H),8.04-8.02(m,2H),7.74-7.7 2(m,1H),7.37-7.35(m,1H),4.48-4.42(m,1H),3.57-3.42(m,3H),3.23-3.20(m,1H),2.15-2.07(m,1H),1.97-1.91(m,1H),1.40(s,9H). ESI-MS: 408.4 [M+H] +

[0495] (2) Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-(pyrrolidin-3-yl)benzamide dihydrochloride [191-2] (hereinafter referred to as compound [191-2])

[0496] TIFF0007734129000154.tif2548

[0497] To a solution of compound [191-1] (794 mg) in ethyl acetate (3.25 mL), a 4 M solution of hydrogen chloride in ethyl acetate (3.25 mL) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure to give the title compound (540 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:9.19(br,2H),8.91-8.86(m,1H),8.66-8.64(m,1H),8.39-8.28(m,1H),8.19-8.04(m,4H) ),7.98-7.79(m,1H),7.38-7.37(m,1H),4.56-4.55(m,1H),3.40-3.21(m,4H),2.23-2.15(m,1H),2.05-1.99(m,1H). ESI-MS: 308.3 [M+H] +

[0498] (3) Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)pyrrolidin-3-yl]benzamide

[0191] To a solution of compound [191-2] (20.0 mg) in NMP (300 μL), potassium carbonate (26.0 mg) and 2-chloropyrimidine (11.0 mg) were added at room temperature, and the mixture was stirred at 140° C. for 4 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (9.6 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.76(d,J=6.9Hz,1H),8.59(d,J=5.5Hz,1H),8.34(d,J=4.6Hz,2H),8.24(d,J=2.5Hz,1H),8.11-8.08(m,2H),8.05-8 .03(m,2H),7.73-7.72(m,1H),7.36-7.35(m,1H),6.61-6.59(m,1H),4.6 3-4.59(m,1H),3.83-3.53(m,4H),2.29-2.22(m,1H),2.29-2.04(m,1H). ESI-MS: 386.4 [M+H] +

[0499] Example 192 Synthesis of (R)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)pyrrolidin-3-yl]benzamide

[0192] (hereinafter referred to as compound

[0192] )

[0500] TIFF0007734129000155.tif3651

[0501] (1) Synthesis of (R)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]pyrrolidine-1-carboxylate tert-butyl [192-1] (hereinafter referred to as compound [192-1])

[0502] TIFF0007734129000156.tif3051

[0503] To a solution of compound [99-1] (100 mg) in dichloromethane (0.80 mL), 4-dimethylaminopyridine (54 mg), EDC (84 mg), and (S)-3-aminopyrrolidine-1-carboxylate tert-butyl (83 μL) were added at room temperature, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (160 mg) as a yellow oil. ESI-MS: 408.4 [M+H] +

[0504] (2) Synthesis of (R)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)pyrrolidin-3-yl]benzamide

[0192] The title compound (4.2 mg) was synthesized as a yellow solid from the compound [192-1] according to the methods of steps (2) and (3) of Example 191. ESI-MS: 386.4 [M+H] +

[0505] Example 193 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0193] (hereinafter referred to as compound

[0193] )

[0506] TIFF0007734129000157.tif4652

[0507] To a solution of compound [191-2] (13.5 mg) in NMP (150 μL), potassium carbonate (17.7 mg) and (2-chloropyrimidin-5-yl)methanol (11.0 mg) were added at room temperature, and the mixture was stirred at 120° C. for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (8.0 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.73(d,J=6.4Hz,1H),8.56(d,J=5.5Hz,1H),8.28(d,J=4.6Hz,2 H),8.21(d,J=2.3Hz,1H),8.07(d,J=8.7Hz,2H),8.01(d,J=8.2Hz,2H),7.70(dd,J=5.5,0.9 Hz,1H),7.35-7.34(m,1H),5.01(t,J=5.5Hz,1H),4.64-4.57(m,1H),4.32-4.30(m,2H),3.8 4-3.80(m,1H),3.72-3.66(m,1H),3.60-3.50(m,2H),2.30-2.22(m,1H),2.12-2.04(m,1H). ESI-MS: 416.4 [M+H] +

[0508] Examples 194 to 197 The compounds of Examples 194 to 197 shown in the table below were synthesized according to the method shown in Example 193. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0509] [Table 5]

[0510] Example 198 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(hydroxymethyl)pyrazin-2-yl]pyrrolidin-3-yl}benzamide

[0198] (hereinafter referred to as compound

[0198] )

[0511] TIFF0007734129000159.tif4652

[0512] To a solution of compound [191-2] (20 mg) in NMP (0.50 mL), cesium carbonate (94 mg) and (5-chloropyrazin-2-yl)methanol (13 mg) were added at room temperature, and the mixture was stirred at 120°C for 23 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (5.2 mg) as a white solid. ESI-MS: 416.4 [M+H] +

[0513] Example 199 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2,2,2-trifluoroethyl)pyrrolidin-3-yl]benzamide

[0199] (hereinafter referred to as compound

[0199] )

[0514] TIFF0007734129000160.tif3055

[0515] To a solution of compound [191-2] (20 mg) in 1,4-dioxane (0.30 mL), DIPEA (15 μL) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (6.3 μL) were added at room temperature, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (2.1 mg) as a white solid. ESI-MS: 390.3 [M+H] +

[0516] Example 200 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(2-hydroxypropan-2-yl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0200] (hereinafter referred to as compound

[0200] )

[0517] TIFF0007734129000161.tif4154

[0518] (1) Synthesis of (S)-2-{3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]pyrrolidin-1-yl}pyrimidine-5-carboxylate ethyl [200-1] (hereinafter referred to as compound [200-1])

[0519] TIFF0007734129000162.tif4156

[0520] To a solution of compound [191-2] (20 mg) in NMP (0.30 mL), potassium carbonate (29 mg) and ethyl 2-chloropyrimidine-5-carboxylate (24 mg) were added at room temperature, and the mixture was stirred at 120°C for 3 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (31 mg) as a yellow solid. ESI-MS: 458.4 [M+H] +

[0521] (2) Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(2-hydroxypropan-2-yl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0200]

[0522] To a solution of compound [200-1] (10 mg) in THF (0.20 mL), a 3 M solution of methylmagnesium bromide in diethyl ether (0.24 mL) was added at 0°C and stirred at room temperature for 3 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (3.8 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.71(d,J=6.9Hz,1H),8.56(d,J=5.9Hz,1H),8.39(s,2H),8.28-8.18(m,1H),8.07(d,J=8.2Hz,2H),8.01(d,J=8.2Hz,2 H),7.70(d,J=5.5Hz,1H),7.36-7.35(m,1H),5.01(s,1H),4.59-4.55(m,1 H),3.80-3.48(m,4H),2.25-2.21(m,1H),2.07-2.02(m,1H),1.37(s,6H). ESI-MS: 444.4 [M+H] +

[0523] Example 201 Synthesis of (S)—N-[1-(5-cyanopyrimidin-2-yl)pyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0201] (hereinafter referred to as compound

[0201] )

[0524] TIFF0007734129000163.tif4154

[0525] (1) Synthesis of (S)—N-[1-(5-bromopyrimidin-2-yl)pyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide [201-1] (hereinafter referred to as compound [201-1])

[0526] TIFF0007734129000164.tif4151

[0527] To a solution of compound [191-2] (30 mg) in NMP (0.30 mL), potassium carbonate (54 mg) and 5-bromo-2-chloropyrimidine (28 mg) were added at room temperature, and the mixture was stirred at 120°C for 3 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (15 mg) as a yellow solid. ESI-MS: 464.5 [M+H] +

[0528] Synthesis of (S)-N-[1-(5-cyanopyrimidin-2-yl)pyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0201] To a solution of compound [201-1] (13.4 mg) in DMF (0.60 mL), zinc cyanide (8.0 mg) and Pd(PPh3)4 (8.0 mg) were added at room temperature, and the mixture was stirred at 120 °C for 30 minutes using a microwave reactor under an argon atmosphere. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (8.0 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.81-8.76(m,3H),8.59(d,J=5.5Hz,1H),8.24(d,J=2.3Hz,1H),8.10(d,J=8.2Hz,2H),8.03(d,J=8.7H) z,2H),7.72(dd,J=5.5,0.9Hz,1H),7.36-7.35(m,1H),4.66-4.62(m,1H),3.88-3.64(m,4H),2.32-2.24(m,1H),2.16-2.08(m,1H). ESI-MS: 411.3 [M+H] +

[0529] Example 202 Synthesis of (S)-2-{3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]pyrrolidin-1-yl}pyrimidine-5-carboxamide

[0202] (hereinafter referred to as compound

[0202] )

[0530] TIFF0007734129000165.tif4155

[0531] To a solution of compound

[0201] (5.1 mg) in tert-butanol (0.30 mL), potassium tert-butoxide (16 mg) was added at room temperature and stirred at 80°C for 6 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (1.5 mg) as a white solid. ESI-MS: 429.3 [M+H] +

[0532] Example 203 Synthesis of N-{(3R,4R)-4-fluoro-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0203] (hereinafter referred to as compound

[0203] )

[0533] TIFF0007734129000166.tif4652

[0534] (1) Synthesis of (3R,4R)-3-fluoro-4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]pyrrolidine-1-carboxylate tert-butyl [203-1] (hereinafter referred to as compound [203-1])

[0535] TIFF0007734129000167.tif3661

[0536] To a solution of compound [99-1] (176 mg) in dichloromethane (2.10 mL), 4-dimethylaminopyridine (63.0 mg), EDC (98.0 mg), and tert-butyl (3R,4R)-3-amino-4-fluoropyrrolidine-1-carboxylate (100 mg) were added at room temperature, and the mixture was stirred at room temperature for 7 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (208 mg) as a yellow oil. ESI-MS: 426.4 [M+H] +

[0537] (2) Synthesis of N-[(3R,4R)-4-fluoropyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide dihydrochloride [203-2] (hereinafter referred to as compound [203-2])

[0538] TIFF0007734129000168.tif2548

[0539] To a solution of compound [203-1] (208 mg) in ethyl acetate (1.20 mL), a 4 M solution of hydrogen chloride in ethyl acetate (1.20 mL) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes. The reaction mixture was concentrated under reduced pressure to give the title compound (170 mg) as a white solid. ESI-MS: 326.3 [M+H] +

[0540] (3) Synthesis of N-{(3R,4R)-4-fluoro-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0203] To a solution of compound [203-2] (49.0 mg) in NMP (500 μL), cesium carbonate (169 mg) and (2-chloropyrimidin-5-yl)methanol (15.0 mg) were added at room temperature, and the mixture was stirred at 120° C. for 19 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (15.2 mg) as a white solid. 1 H-NMR(400MHz,CD3OD)δ:8.52(d,J=5.9Hz,1H),8.38(s,2H),8.03-7.98(m,5H),7.63(d,J=5.9Hz,1H),7.19 (d,J=2.1Hz,1H),5.38-5.32(m,1H),4.84-4.77(m,1H),4.48(s,2H),4.05-3.98(m,2H),3.90-3.88(m,2H). ESI-MS: 434.4 [M+H] +

[0541] Example 204 Synthesis of N-{(3R,4S)-4-fluoro-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0204] (hereinafter referred to as compound

[0204] )

[0542] TIFF0007734129000169.tif4146

[0543] (1) Synthesis of (3S,4R)-3-fluoro-4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]pyrrolidine-1-carboxylate tert-butyl [204-1] (hereinafter referred to as compound [204-1])

[0544] TIFF0007734129000170.tif3051

[0545] To a solution of compound [99-1] (176 mg) in dichloromethane (2.10 mL), 4-dimethylaminopyridine (63.0 mg), EDC (98.0 mg), and tert-butyl (3S,4R)-3-amino-4-fluoropyrrolidine-1-carboxylate (100 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (188 mg) as a yellow oil. ESI-MS: 426.4 [M+H] +

[0546] (2) Synthesis of N-{(3R,4S)-4-fluoro-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0204] The title compound was synthesized from the compound [204-1] according to the methods of steps (2) and (3) of Example 203. 1 H-NMR(400MHz,DMSO-d6)δ:8.81(d,J=6.9Hz,1H),8.57(d,J=5.5Hz,1H),8.31(s,2H),8.22(d,J=2.3Hz,1H),8.15-8.09(m,4H),7.71(d, J=5.9Hz,1H),7.36(d,J=2.3Hz,1H),5.44-5.26(m,1H),5.05(t,J=5.5Hz,1H),4.81-4.74(m,1H),4.32-4.30(m,2H),3.96-3.60(m,4H). ESI-MS: 434.3 [M+H] +

[0547] Example 205 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4R)-1-[5-(hydroxymethyl)pyrimidin-2-yl]-4-methoxypyrrolidin-3-yl}benzamide

[0205] (hereinafter referred to as compound

[0205] )

[0548] TIFF0007734129000171.tif4147

[0549] (1) Synthesis of (3R,4R)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]-4-methoxypyrrolidine-1-carboxylate tert-butyl [205-1] (hereinafter referred to as compound [205-1])

[0550] TIFF0007734129000172.tif3051

[0551] To a solution of compound [99-1] (102 mg) in dichloromethane (1.00 mL), 4-dimethylaminopyridine (37.0 mg), EDC (58.0 mg), and tert-butyl (3R,4R)-3-amino-4-methoxypyrrolidine-1-carboxylate (62.0 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (109 mg) as a colorless oil. ESI-MS: 438.7 [M+H] +

[0552] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4R)-1-[5-(hydroxymethyl)pyrimidin-2-yl]-4-methoxypyrrolidin-3-yl}benzamide

[0205] The title compound was synthesized from the compound [205-1] according to the methods of steps (2) and (3) of Example 203. 1H-NMR(400MHz,DMSO-d6)δ:8.80(d,J=6.4Hz,1H),8.59-8.58(m,1H),8.31(s,2 H),8.24-8.23(m,1H),8.09(d,J=8.7Hz,2H),8.04(d,J=8.7Hz,2H),7.73-7.71 (m,1H),7.36-7.35(m,1H),5.05(t,J=5.7Hz,1H),4.59-4.56(m,1H),4.33-4.3 2(m,2H),4.00-3.97(m,1H),3.82-3.73(m,2H),3.67-3.61(m,2H),3.39(s,3H). ESI-MS: 446.3 [M+H] +

[0553] Example 206 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4S)-1-[5-(hydroxymethyl)pyrimidin-2-yl]-4-methoxypyrrolidin-3-yl}benzamide

[0206] (hereinafter referred to as compound

[0206] )

[0554] TIFF0007734129000173.tif4652

[0555] (1) Synthesis of (3R,4S)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]-4-methoxypyrrolidine-1-carboxylate tert-butyl [206-1] (hereinafter referred to as compound [206-1])

[0556] TIFF0007734129000174.tif3661

[0557] To a solution of compound [99-1] (85 mg) in dichloromethane (1.0 mL), 4-dimethylaminopyridine (29 mg), EDC (46 mg), and tert-butyl (3R,4S)-3-amino-4-methoxypyrrolidine-1-carboxylate (50 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (96 mg) as a yellow oil. ESI-MS: 438.4 [M+H] +

[0558] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4S)-1-[5-(hydroxymethyl)pyrimidin-2-yl]-4-methoxypyrrolidin-3-yl}benzamide

[0206] The title compound was synthesized from the compound [206-1] according to the methods of steps (2) and (3) of Example 203. 1 H-NMR(400MHz,DMSO-d6)δ:8.68-8.52(m,2H),8.31(s,2H),8.24(d,J=2.3Hz,1H),8.12-8.07(m,4H),7.73(dd,J=5.5,0.9Hz,1H),7.39-7.3 8(m,1H),5.05(t,J=5.5Hz,1H),4.75-4.72(m,1H),4.33-4.31(m,2H), 4.12-4.09(m,1H),3.86-3.77(m,2H),3.65-3.57(m,2H),3.32(s,3H). ESI-MS: 446.3 [M+H] +

[0559] Example 207 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4R)-4-hydroxy-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0207] (hereinafter referred to as compound

[0207] )

[0560] TIFF0007734129000175.tif4652

[0561] (1) Synthesis of (3R,4R)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]-4-hydroxypyrrolidine-1-carboxylate tert-butyl [207-1] (hereinafter referred to as compound [207-1])

[0562] TIFF0007734129000176.tif3661

[0563] To a solution of compound [99-1] (176 mg) in dichloromethane (2.00 mL), 4-dimethylaminopyridine (62.0 mg), EDC (98.0 mg), and tert-butyl (3R,4R)-3-amino-4-hydroxypyrrolidine-1-carboxylate (100 mg) were added at room temperature, and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (91.0 mg) as a brown oil. ESI-MS: 424.3 [M+H] +

[0564] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4R)-4-hydroxy-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0207] The title compound was synthesized from the compound [207-1] according to the methods of steps (2) and (3) of Example 203. 1H-NMR(400MHz,DMSO-d6)δ:8.68(d,J=5.9Hz,1H),8.58(d,J=5.5Hz,1H),8. 30(s,2H),8.24(s,1H),8.09(d,J=6.9Hz,2H),8.03(d,J=6.9Hz,2H),7.72( d,J=5.5Hz,1H),7.36-7.34(m,1H),5.43-5.42(m,1H),5.05-5.03(m,1H),4 .45-4.28(m,4H),3.86-3.72(m,2H),3.61-3.58(m,1H),3.49-3.46(m,1H). ESI-MS: 432.3 [M+H] +

[0565] Example 208 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4S)-4-hydroxy-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0208] (hereinafter referred to as compound

[0208] )

[0566] TIFF0007734129000177.tif4146

[0567] (1) Synthesis of (3R,4S)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]-4-hydroxypyrrolidine-1-carboxylate tert-butyl [208-1] (hereinafter referred to as compound [208-1])

[0568] TIFF0007734129000178.tif3051

[0569] To a solution of compound [99-1] (177 mg) in dichloromethane (2.00 mL), 4-dimethylaminopyridine (63.0 mg), EDC (99.0 mg), and tert-butyl (3R,4S)-3-amino-4-hydroxypyrrolidine-1-carboxylate (100 mg) were added at room temperature, and the mixture was stirred at room temperature for 19 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (167 mg) as a colorless oil. ESI-MS: 424.3 [M+H] +

[0570] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{(3R,4S)-4-hydroxy-1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide

[0208] The title compound was synthesized from the compound [208-1] according to the methods of steps (2) and (3) of Example 203. 1 H-NMR(400MHz,DMSO-d6)δ:8.60(d,J=5.5Hz,1H),8.39(d,J=7.3Hz,1H),8.30 (s,2H),8.25(d,J=2.3Hz,1H),8.14-8.08(m,4H),7.73(dd,J=5.7,1.1Hz,1H), 7.39-7.38(m,1H),5.36-5.34(m,1H),5.03(t,J=5.5Hz,1H),4.61-4.49(m,1H ),4.40-4.37(m,1H),4.32-4.31(m,2H),3.87-3.83(m,1H),3.63-3.52(m,3H). ESI-MS: 432.3 [M+H] +

[0571] Example 209 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(2-azaspiro[3.3]heptan-6-yl)benzamide

[0209] (hereinafter referred to as compound

[0209] )

[0572] TIFF0007734129000179.tif2142

[0573] (1) Synthesis of tert-butyl 6-[4-(furo[3,2-c]pyridin-4-yl)benzamido]-2-azaspiro[3.3]heptane-2-carboxylate [209-1] (hereinafter referred to as compound [209-1])

[0574] TIFF0007734129000180.tif2651

[0575] To a solution of compound [99-1] (200 mg) in dichloromethane (3.00 mL), 4-dimethylaminopyridine (110 mg), EDC (170 mg), and tert-butyl 6-amino-2-azaspiro[3.3]heptane-2-carboxylate (234 mg) were added at room temperature, and the mixture was stirred at room temperature for 24 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (317 mg) as a yellow solid. ESI-MS: 434.5 [M+H] +

[0576] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(2-azaspiro[3.3]heptan-6-yl)benzamide

[0209] To a solution of compound [209-1] (317 mg) in dichloromethane (2.00 mL), trifluoroacetic acid (3.00 mL) was added at room temperature, and the mixture was stirred at room temperature for 22 hours. A 5M aqueous solution of sodium hydroxide was added to the reaction mixture at 0°C, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (100 mg) as a white solid. ESI-MS: 334.4 [M+H] +

[0577] Example 210 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[2-(pyrimidin-2-yl)-2-azaspiro[3.3]heptan-6-yl]benzamide

[0210] (hereinafter referred to as compound

[0210] )

[0578] TIFF0007734129000181.tif3665

[0579] To a solution of compound

[0209] (10 mg) in NMP (0.30 mL), potassium carbonate (12 mg) and 2-chloropyrimidine (4.5 mg) were added at room temperature, and the mixture was stirred at 140°C for 2 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (3.0 mg) as a brown solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.76(d,J=7.3Hz,1H),8.59(d,J=5.5Hz,1H),8. 33-8.30(m,2H),8.24(d,J=2.3Hz,1H),8.10(d,J=8.7Hz,2H),8.02(d,J=8.2 Hz,2H),7.76-7.68(m,1H),7.38-7.37(m,1H),6.64(t,J=4.8Hz,1H),4.42-4 .36(m,1H),4.11(s,2H),4.00(s,2H),2.61-2.57(m,2H),2.38-2.34(m,2H). ESI-MS: 412.4 [M+H] +

[0580] Example 211 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(3R,6S)-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]benzamide

[0211] (hereinafter referred to as compound

[0211] )

[0581] TIFF0007734129000182.tif2556

[0582] To a solution of tert-butyl N-[(3R,6S)-6-(hydroxymethyl)oxan-3-yl]carbamate (200 mg) in ethyl acetate (650 μL), a 4 M solution of hydrogen chloride in ethyl acetate (650 μL) was added at room temperature, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure. To a solution of the resulting residue in dichloromethane (1.6 mL), 4-dimethylaminopyridine (62 mg), EDC (97 mg), and compound [99-1] (120 mg) were added at room temperature, and the mixture was stirred at room temperature for 1 hour. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (78 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.60-8.57(m,1H),8.34(d,J=5.9Hz,1H),8.25 -8.23(m,1H),8.10-8.08(m,2H),8.02-8.00(m,2H),7.74-7.72(m,1H),7.3 6-7.35(m,1H),4.65-4.63(m,1H),3.92-3.90(m,2H),3.40-3.24(m,3H),3 .19-3.12(m,1H),1.99-1.96(m,1H),1.75-1.58(m,2H),1.36-1.27(m,1H). ESI-MS: 353.3 [M+H] +

[0583] Example 212 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(3R,6S)-6-(1-hydroxyethyl)tetrahydro-2H-pyran-3-yl]benzamide

[0212] (hereinafter referred to as compound

[0212] )

[0584] TIFF0007734129000183.tif3063

[0585] To a solution of compound

[0211] (26.1 mg) in dichloromethane (600 μL), 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) (47.0 mg) was added at room temperature, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the resulting residue in THF (300 μL), a 3 M solution of methylmagnesium bromide in diethyl ether (114 μL) was added at 0°C, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (15.3 mg) as a white solid. ESI-MS: 367.3 [M+H] +

[0586] Example 213 Synthesis of N-[(3R,6S)-6-acetyltetrahydro-2H-pyran-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0213] (hereinafter referred to as compound

[0213] )

[0587] TIFF0007734129000184.tif3059

[0588] To a solution of compound

[0212] (11.0 mg) in dichloromethane (500 μL), 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) (19.0 mg) was added at room temperature, and the mixture was stirred at room temperature for 4 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (10.2 mg) as a white solid. ESI-MS: 365.4 [M+H] +

[0589] Example 214 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(3R,6S)-6-(2-hydroxypropan-2-yl)tetrahydro-2H-pyran-3-yl]benzamide

[0214] (hereinafter referred to as compound

[0214] )

[0590] TIFF0007734129000185.tif3063

[0591] To a solution of compound

[0213] (9.0 mg) in THF (0.30 mL), a 3 M solution of methylmagnesium bromide in diethyl ether (246 μL) was added at 0° C., and the mixture was stirred at room temperature for 3 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by preparative thin-layer chromatography to give the title compound (1.6 mg) as a white solid. 1 H-NMR(400MHz,CD3OD)δ:8.51(d,J=5.5Hz,1H),8.01-7.97(m,5H),7.63(d,J=5.9Hz,1H),7.19-7.18(m,1 H),4.10-4.04(m,2H),3.25-3.09(m,2H),2.18-2.00(m,2H),1.67-1.46(m,2H),1.18(s,3H),1.16(s,3H). ESI-MS: 381.3 [M+H] +

[0592] Example 215 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(1R,3R)-3-(2-hydroxypropan-2-yl)cyclopentyl]benzamide

[0215] (hereinafter referred to as compound

[0215] )

[0593] TIFF0007734129000186.tif3152

[0594] (1) Synthesis of (1R,3R)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]cyclopentane-1-carboxylate methyl [215-1] (hereinafter referred to as compound [215-1])

[0595] TIFF0007734129000187.tif3656

[0596] To a solution of compound [99-1] (185 mg) in dichloromethane (2.00 mL), 4-dimethylaminopyridine (72.0 mg), EDC (113 mg), and (1R,3R)-3-aminocyclopentane-1-carboxylate methyl ester hydrochloride (100 mg) were added at room temperature, and the mixture was stirred at room temperature for 22 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (114 mg) as a white solid. ESI-MS: 365.3 [M+H] +

[0597] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(1R,3R)-3-(2-hydroxypropan-2-yl)cyclopentyl]benzamide

[0215] To a solution of compound [215-1] (20.0 mg) in THF (300 μL), a 3M solution of methylmagnesium bromide in diethyl ether (367 μL) was added at room temperature, and the mixture was stirred at room temperature for 24 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (7.4 mg) as a yellow solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59-8.58(m,1H),8.35(d,J=7.3Hz,1H),8.21(d,J=2.3Hz,1H),8.10-8.03(m,2H),8.02-8.00(m,2) H),7.69(dd,J=6.2,5.3Hz,1H),7.36-7.35(m,1H),4.26-4.20(m,1H),4.06-4.05(m,1H),2.17-1.40(m,7H),1.08-1.00(m,6H). ESI-MS: 365.3 [M+H] +

[0598] Example 216 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(1S,3S)-3-(2-hydroxypropan-2-yl)cyclopentyl]benzamide

[0216] (hereinafter referred to as compound

[0216] )

[0599] TIFF0007734129000188.tif3152

[0600] (1) Synthesis of (1S,3S)-3-[4-(furo[3,2-c]pyridin-4-yl)benzamido]cyclopentane-1-carboxylate methyl [216-1] (hereinafter referred to as compound [216-1])

[0601] TIFF0007734129000189.tif3656

[0602] To a solution of compound [99-1] (93 mg) in dichloromethane (1.0 mL), 4-dimethylaminopyridine (36 mg), EDC (57 mg), and (1S,3S)-3-aminocyclopentane-1-carboxylate methyl ester hydrochloride (50 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (43 mg) as a white solid. ESI-MS: 365.3 [M+H]+

[0603] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(1S,3S)-3-(2-hydroxypropan-2-yl)cyclopentyl]benzamide

[0216] The title compound was synthesized from the compound [216-1] according to the method of step (2) of Example 215. 1 H-NMR(400MHz, CDCl3)δ:8.60-8.58(m,1H),7.99(d,J=8.2Hz,2H),7.91-7. 89(m,2H),7.72(d,J=1.8Hz,1H),7.47-7.45(m,1H),7.03(d,J=2.3Hz,1H), 6.24(d,J=7.3Hz,1H),4.47-4.42(m,1H),3.70-3.64(m,1H),2.23-2.16(m, 2H),2.20-1.98(m,1H),1.89-1.83(m,1H),1.73-1.51(m,3H),1.20(s,6H). ESI-MS: 365.3 [M+H] +

[0604] Example 217 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)azetidin-3-yl]benzamide

[0217] (hereinafter referred to as compound

[0217] )

[0605] TIFF0007734129000190.tif3055

[0606] To a solution of compound [99-1] (20 mg) in dichloromethane (0.30 mL), 4-dimethylaminopyridine (11 mg), EDC (17 mg), and 1-(pyrimidin-2-yl)azetidin-3-amine dihydrochloride (25 mg) were added at room temperature, and the mixture was stirred at room temperature for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (14 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:9.19(d,J=7.3Hz,1H),8.59(d,J=5.9Hz,1H),8.37(d,J=4.6Hz,2H),8.24(d,J=2.3Hz,1H),8.12(d,J=8.2Hz,2H),8.06(d,J =8.7Hz,2H),7.73(dd,J=5.5,0.9Hz,1H),7.39-7.38(m,1H),6.69(t,J=4.8 Hz,1H),4.94-4.84(m,1H),4.38-4.34(m,2H),4.07(dd,J=9.1,5.5Hz,2H). ESI-MS: 372.4 [M+H] +

[0607] Example 218 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(trans-3-hydroxycyclobutyl)methyl]benzamide

[0218] (hereinafter referred to as compound

[0218] )

[0608] TIFF0007734129000191.tif2559

[0609] The title compound was obtained as a white solid according to the method of Example 217. 1H-NMR(400MHz,DMSO-d6)δ:8.62-8.58(m,2H),8.24(d,J=2.3Hz,1H),8.09(dd,J=6.6,2.1Hz,2H),8.02-7.99(m,2H),7.72(dd,J=5.7,1.1Hz, 1H),7.38-7.37(m,1H),4.94(d,J=6.4Hz,1H),4.27-4.18(m,1H),3.35 -3.33(m,2H),2.38-2.31(m,1H),2.08-2.02(m,2H),1.93-1.86(m,2H). ESI-MS: 323.3 [M+H] +

[0610] Example 219 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[(cis-3-hydroxycyclobutyl)methyl]benzamide

[0219] (hereinafter referred to as compound

[0219] )

[0611] TIFF0007734129000192.tif2560

[0612] The title compound was obtained as a white solid according to the method of Example 217. 1 H-NMR(400MHz,DMSO-d6)δ:8.59-8.56(m,2H),8.24(d,J=2.3Hz,1H),8.09(d,J=8.7Hz,2H),8.02-8.00(m,2H),7.72(dd,J=5.5,0.9Hz,1H),7.3 7(dd,J=1.1,1.1Hz,1H),4.93(d,J=6.9Hz,1H),3.93-3.84(m,1H),3.29 -3.27(d,2H),2.27-2.21(m,2H),1.99-1.90(m,1H),1.58-1.51(m,2H). ESI-MS: 323.4 [M+H] +

[0613] Example 220 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[2-hydroxy-1-(pyridin-2-yl)ethyl]benzamide

[0220] (hereinafter referred to as compound

[0220] )

[0614] TIFF0007734129000193.tif3158

[0615] The title compound was obtained as a yellow solid according to the method of Example 217. 1 H-NMR(400MHz,DMSO-d6)δ:8.81(d,J=8.0Hz,1H),8.60(d,J=5.3Hz,1H),8.54(d,J=4.6Hz,1H),8.25(d,J=2.3Hz,1H),8.18-8.06(m,4H),7.80-7. 70(m,2H),7.44(d,J=8.2Hz,1H),7.38(d,J=1.1Hz,1H),7.29-7.25(m,1H ),5.18(dd,J=12.8,7.8Hz,1H),4.96(t,J=5.9Hz,1H),3.89-3.77(m,2H). ESI-MS: 360.3 [M+H] +

[0616] Example 221 Synthesis of N-(chroman-3-ylmethyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0221] (hereinafter referred to as compound

[0221] )

[0617] TIFF0007734129000194.tif2562

[0618] To a solution of compound [99-1] (358 mg) in dichloromethane (4.30 mL), 4-dimethylaminopyridine (128 mg), EDC (201 mg), and chroman-3-ylmethanamine hydrochloride (200 mg) were added at room temperature, and the mixture was stirred at room temperature for 16 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (313 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.76-8.73(m,1H),8.56(d,J=5.5Hz,1H),8.21(d,J=2.3Hz,1 H),8.08(d,J=8.2Hz,2H),8.02(d,J=8.7Hz,2H),7.73-7.66(m,1H),7.36-7.35(m,1H),7 .06-7.01(m,2H),6.79(t,J=7.3Hz,1H),6.72(d,J=8.2Hz,1H),4.22-4.19(m,1H),3.88- 3.83(m,1H),3.36-3.31(m,2H),2.89-2.82(m,1H),2.62-2.56(m,1H),2.34-2.31(m,1H). ESI-MS: 385.3 [M+H] +

[0619] Example 222 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{4-[4-(morpholine-4-carbonyl)piperidin-1-yl]phenyl}benzamide

[0222] (hereinafter referred to as compound

[0222] )

[0620] TIFF0007734129000195.tif3060

[0621] (1) Synthesis of 1-(4-nitrophenyl)piperidine-4-carboxylic acid [222-1] (hereinafter referred to as compound [222-1])

[0622] TIFF0007734129000196.tif2542

[0623] To a solution of 4-fluoronitrobenzene (3.95 g) in acetonitrile (40 mL), ethyl 4-piperidinecarboxylate (4.75 mL) and potassium carbonate (9.70 g) were added at room temperature, and the mixture was stirred at 60°C for 9 hours. The mixture was then stirred at room temperature for 20 hours. The reaction mixture was concentrated under reduced pressure, followed by addition of water and extraction with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the resulting residue in ethanol (70 mL), 2 M aqueous sodium hydroxide solution (28 mL) was added at room temperature, and the mixture was stirred at room temperature for 41 hours. 5 M aqueous sodium hydroxide solution (20 mL) was then added at room temperature, and the mixture was stirred at 100°C for 2 hours. The reaction mixture was cooled to 0°C, concentrated hydrochloric acid was added, and the resulting solid was collected by filtration and dried under reduced pressure to obtain the title compound (6.78 g) as a yellow solid. ESI-MS: 251.1 [M+H] +

[0624] (2) Synthesis of morpholino[1-(4-nitrophenyl)piperidin-4-yl]methanone [222-2] (hereinafter referred to as compound [222-2]) TIFF0007734129000197.tif2546

[0625] To a solution of compound [222-1] (1.00 g) in DMF (15 mL), morpholine (522 μL), DIPEA (1.39 mL), and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (2.57 g) were added at 0° C., and the mixture was stirred at 0° C. for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was suspended in ethyl acetate / diethyl ether, and the solid was collected by filtration to give the title compound (954 mg) as a yellow solid. ESI-MS: 320.2 [M+H] +

[0626] (3) Synthesis of [1-(4-aminophenyl)piperidin-4-yl](morpholino)methanone dihydrochloride [222-3] (hereinafter referred to as compound [222-3])

[0627] TIFF0007734129000198.tif2546

[0628] To a solution of compound [222-2] (954 mg) in THF (25 mL) / methanol (20 mL), 10% palladium on activated carbon (320 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 10 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. To a solution of the resulting residue in ethyl acetate (20 mL), a 4 M solution of hydrogen chloride in ethyl acetate (2.00 mL) was added at room temperature, and the mixture was stirred at room temperature for 15 minutes. The resulting solid was collected by filtration and dried under reduced pressure to obtain the title compound (1.04 g) as a white solid. ESI-MS: 290.2 [M+H] +

[0629] (4) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{4-[4-(morpholine-4-carbonyl)piperidin-1-yl]phenyl}benzamide

[0222] To a solution of compound [99-1] (30 mg) in DMF (0.42 mL), DIPEA (85 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (59 mg), and compound [222-3] (59 mg) were added at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (41 mg) as a yellow solid. ESI-MS: 511.2 [M+H] +

[0630] Example 223 Synthesis of N-{3-fluoro-4-[4-(morpholine-4-carbonyl)piperidin-1-yl]phenyl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0223] (hereinafter referred to as compound

[0223] )

[0631] TIFF0007734129000199.tif3060

[0632] The title compound was synthesized from 3,4-difluoronitrobenzene according to the methods of steps (1), (2), (3) and (4) of Example 222. ESI-MS: 529.2 [M+H] +

[0633] Example 224 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[4-(pyrimidin-2-yl)-1,4-oxazepan-6-yl]benzamide

[0224] (hereinafter referred to as compound

[0224] )

[0634] TIFF0007734129000200.tif3645

[0635] (1) Synthesis of (S)-tert-butyl 6-[4-(furo[3,2-c]pyridin-4-yl)benzamido]-1,4-oxazepane-4-carboxylate [224-1] (hereinafter referred to as compound [224-1])

[0636] TIFF0007734129000201.tif3541

[0637] To a solution of compound [99-1] (100 mg) in dichloromethane (1.4 mL), 4-dimethylaminopyridine (56 mg), EDC (88 mg), and (S)-6-amino-1,4-oxazepane-6-carboxylate tert-butyl (108 mg) were added at room temperature, and the mixture was stirred at room temperature for 23 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (89 mg) as a colorless oil. ESI-MS: 438.2 [M+H] +

[0638] (2) Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-(1,4-oxazepan-6-yl)benzamide dihydrochloride [224-2] (hereinafter referred to as compound [224-2])

[0639] TIFF0007734129000202.tif2540

[0640] To a solution of compound [224-1] (89 mg) in ethyl acetate (0.5 mL), a 4 M solution of hydrogen chloride in ethyl acetate (0.4 mL) was added at room temperature, and the mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure to give the title compound (82 mg) as a yellow solid. ESI-MS: 338.2 [M+H] +

[0641] (3) Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[4-(pyrimidin-2-yl)-1,4-oxazepan-6-yl]benzamide

[0224] To a solution of compound [224-2] (14.0 mg) in NMP (0.5 mL), cesium carbonate (139 mg) and 2-chloropyrimidine (15.0 mg) were added at room temperature, and the mixture was stirred at 120°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (6.70 mg) as a yellow solid. ESI-MS: 416.3 [M+H] +

[0642] Example 225 Synthesis of (R)-4-(furo[3,2-c]pyridin-4-yl)-N-[4-(pyrimidin-2-yl)-1,4-oxazepan-6-yl]benzamide

[0225] (hereinafter referred to as compound

[0225] )

[0643] TIFF0007734129000203.tif3645

[0644] The title compound was synthesized by a method similar to Example 224, except that (R)-tert-butyl 6-amino-1,4-oxazepane-6-carboxylate was used instead of tert-butyl (S)-6-amino-1,4-oxazepane-6-carboxylate. ESI-MS: 416.3 [M+H] +

[0645] Example 226 Synthesis of (S)—N-[1-(6-fluoropyridin-2-yl)pyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0226] (hereinafter referred to as compound

[0226] )

[0646] TIFF0007734129000204.tif3049

[0647] The title compound was synthesized by a method similar to Example 193, except that 2,6-difluoropyridine was used instead of (2-chloropyrimidin-5-yl)methanol. ESI-MS: 403.2 [M+H] +

[0648] Example 227 Synthesis of (S)—N-[1-(6-chloropyrimidin-4-yl)pyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0227] (hereinafter referred to as compound

[0227] )

[0649] TIFF0007734129000205.tif3645

[0650] The title compound was synthesized by a method similar to Example 193, except that 4,6-dichloropyrimidine was used instead of (2-chloropyrimidin-5-yl)methanol. ESI-MS: 420.1 [M+H] +

[0651] Example 228 Synthesis of (S)—N-[1-(6-chloropyridazin-3-yl)pyrrolidin-3-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0228] (hereinafter referred to as compound

[0228] )

[0652] TIFF0007734129000206.tif3545

[0653] The title compound was synthesized by a method similar to Example 193, except that 3,6-dichloropyridazine was used instead of (2-chloropyrimidin-5-yl)methanol. ESI-MS: 420.2 [M+H] +

[0654] Example 229 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-4-yl)pyrrolidin-3-yl]benzamide

[0229] (hereinafter referred to as compound

[0229] )

[0655] TIFF0007734129000207.tif3041

[0656] To a solution of compound

[0227] (5.0 mg) in THF (0.3 mL), sodium borohydride (1.4 mg), N,N,N',N'-tetramethylethylenediamine (1.8 μL), and PdCl2(dppf) (9.0 mg) were added at room temperature, and the mixture was stirred at room temperature for 4 hours under an argon atmosphere. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (3.2 mg) as a white solid. ESI-MS: 386.2 [M+H] +

[0657] Example 230 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyridazin-3-yl)pyrrolidin-3-yl]benzamide

[0230] (hereinafter referred to as compound

[0230] )

[0658] TIFF0007734129000208.tif3045

[0659] The title compound was synthesized from compound

[0228] according to the method of Example 229. ESI-MS: 386.2 [M+H] +

[0660] Example 231 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-tetrazol-5-yl)pyrrolidin-3-yl]benzamide

[0231] (hereinafter referred to as compound

[0231] )

[0661] TIFF0007734129000209.tif3044

[0662] To a solution of compound [191-2] (40 mg) in acetonitrile (0.5 mL), methyl isothiocyanate (12 mg) and DIPEA (63 μL) were added at room temperature. The vessel was sealed and stirred at 100°C for 30 minutes. Then, 1,3-propane sultone (22 μL) and triethylamine (53 μL) were added at 100°C. The vessel was sealed and stirred at 100°C for 1 hour. Sodium azide (81 mg) was then added at 100°C. The vessel was sealed and stirred at 100°C for 1 hour. Water was added to the reaction mixture, which was then 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 column chromatography to obtain the title compound (2.3 mg) as a white solid. ESI-MS: 390.2 [M+H] +

[0663] Example 232 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-ethyl-1H-tetrazol-5-yl)pyrrolidin-3-yl]benzamide

[0232] (hereinafter referred to as compound

[0232] )

[0664] TIFF0007734129000210.tif3048

[0665] The title compound was synthesized by a method similar to that of Example 231, except that ethyl isothiocyanate was used instead of methyl isothiocyanate. ESI-MS: 404.2 [M+H] +

[0666] Example 233 Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(6-oxo-1,6-dihydropyridin-2-yl)pyrrolidin-3-yl]benzamide

[0233] (hereinafter referred to as compound

[0233] )

[0667] TIFF0007734129000211.tif3049

[0668] (1) Synthesis of 2-[(2,4-dimethoxybenzyl)oxy]-6-fluoropyridine [233-1] (hereinafter referred to as compound [233-1])

[0669] TIFF0007734129000212.tif2044

[0670] To a solution of 2,4-dimethoxybenzyl alcohol (1.46 g) in DMF (29 mL), 60% sodium hydride (382 mg) and 2,6-difluoropyridine (1.00 g) were added at room temperature, and the mixture was stirred at room temperature for 19 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (2.08 g) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:7.62(dd,J=8.1,8.1Hz,1H),7.35(d,J=8.7Hz,1H),6.63 (dd,J=8.2,1.4Hz,1H),6.49-6.48(m,3H),5.30(s,2H),3.83(s,3H),3.81(s,3H).

[0671] (2) Synthesis of (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(6-oxo-1,6-dihydropyridin-2-yl)pyrrolidin-3-yl]benzamide

[0233] To a solution of compound [191-2] (20 mg) in NMP (0.5 mL), cesium carbonate (101 mg) and compound [233-1] (33 mg) were added at room temperature, and the mixture was stirred at 120°C for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. A 4M solution of hydrogen chloride in ethyl acetate (4.0 mL) was added to the resulting residue at room temperature, and the mixture was stirred at room temperature for 1 hour. 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (5.2 mg) as a white solid. ESI-MS: 401.2 [M+H] +

[0672] Example 234 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(1-propionylpiperidin-4-yl)benzamide

[0234] (hereinafter referred to as compound

[0234] )

[0673] TIFF0007734129000213.tif2547

[0674] To a solution of compound

[0142] (30 mg) in DMF (0.5 mL), propionic acid (12 μL), DIPEA (78 μL), and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (65 mg) were added at room temperature, and the mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (20 mg) as a pink solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.42(d,J=7.8Hz,1H),8.24-8.23(m ,1H),8.11-8.08(m,2H),8.03-8.01(m,2H),7.74-7.71(m,1H),7.37-7.36(m,1H),4.3 9-4.36(m,1H),4.07-4.06(m,1H),3.89-3.86(m,1H),3.15-3.08(m,1H),2.72-2.66(m ,1H),2.37-2.32(m,2H),1.90-1.81(m,2H),1.50-1.38(m,2H),0.99(t,J=7.4Hz,3H). ESI-MS: 378.2 [M+H] +

[0675] Example 235 Synthesis of N-[1-(cyclopropanecarbonyl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0235] (hereinafter referred to as compound

[0235] )

[0676] TIFF0007734129000214.tif2547

[0677] To a solution of compound

[0142] (50 mg) in DMF (1.0 mL), cyclopropanecarboxylic acid (100 μL), DIPEA (100 μL), and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (100 mg) were added at room temperature, and the mixture was stirred at room temperature for 22 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 dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (40 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.43(d,J=7.8Hz,1H),8.2 6-8.22(m,1H),8.10(d,J=7.3Hz,2H),8.02(d,J=7.3Hz,2H),7.74-7.71(m,1H ),7.37-7.36(m,1H),4.36-4.25(m,2H),4.11-4.07(m,1H),3.26-3.19(m,1H) ,2.79-2.65(m,1H),2.05-1.82(m,3H),1.52-1.42(m,2H),0.73-0.69(m,4H). ESI-MS: 390.2 [M+H] +

[0678] Example 236 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(oxetan-3-yl)piperidin-4-yl]benzamide

[0236] (hereinafter referred to as compound

[0236] )

[0679] TIFF0007734129000215.tif2549

[0680] To a solution of compound

[0142] (60 mg) in THF (1.0 mL) / dichloromethane (1.5 mL), DIPEA (103 μL), sodium acetate (17 mg), 3-oxetanone (16 mg), and sodium cyanoborohydride (48 mg) were added at room temperature, and the mixture was stirred at 60° C. for 5 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (18 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.59(dd,J=5.6,3.6Hz,1H),8.40(d,J=6.4Hz,1H),8.24( d,J=3.2Hz,1H),8.09(d,J=8.2Hz,2H),8.01(d,J=8.2Hz,2H),7.73(d,J=5.5Hz,1H),7 .37-7.36(m,1H),4.53(dd,J=6.4,6.2Hz,2H),4.42(dd,J=6.4,6.2Hz,2H),3.88-3.7 5(m,1H),3.41-3.35(m,1H),2.73-2.65(m,2H),1.89-1.80(m,4H),1.64-1.54(m,2H). ESI-MS: 378.2 [M+H] +

[0681] Example 237 Synthesis of N-[1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0237] (hereinafter referred to as compound

[0237] )

[0682] TIFF0007734129000216.tif2545

[0683] To a solution of compound

[0142] (30 mg) in NMP (0.5 mL), cesium carbonate (124 mg) and 2-chloro-1,3,4-thiadiazole (30 mg) were added at room temperature, and the mixture was stirred at 90°C for 20 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (4.2 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.81(s,1H),8.59(d,J=5.5Hz,1H),8.47(d,J=7.8Hz,1H),8.24(d,J=2.3Hz,1H),8.09(d,J=8.7Hz,2H),8.02(d,J=8.7Hz) ,2H),7.72(dd,J=5.7,1.1Hz,1H),7.37-7.36(m,1H),4.17-4.09(m,1H),3 .93-3.89(m,2H),3.30-3.27(m,2H),2.02-1.92(m,2H),1.74-1.64(m,2H). ESI-MS: 406.1 [M+H] +

[0684] Example 238 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(imidazo[1,2-a]pyridin-5-yl)piperidin-4-yl]benzamide

[0238] (hereinafter referred to as compound

[0238] )

[0685] TIFF0007734129000217.tif2550

[0686] The title compound was synthesized by a method similar to Example 237, except that 5-chloroimidazo[1,2-a]pyridine was used instead of 2-chloro-1,3,4-thiadiazole. ESI-MS: 438.2 [M+H] +

[0687] Example 239 Synthesis of N-[1-(1-ethyl-1H-tetrazol-5-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0239] (hereinafter referred to as compound

[0239] )

[0688] TIFF0007734129000218.tif2546

[0689] To a solution of compound

[0142] (100 mg) in acetonitrile (0.83 mL), ethyl isothiocyanate (28 μL) and DIPEA (127 μL) were added at room temperature. The vessel was sealed and stirred at 100°C for 30 minutes. 1,3-propanesultone (44 μL) and triethylamine (104 μL) were then added at 100°C. The vessel was sealed and stirred at 100°C for 1 hour. Sodium azide (163 mg) was then added at 100°C. The vessel was sealed and stirred at 100°C for 1 hour. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (15 mg) as a white solid. ESI-MS: 418.2 [M+H] +

[0690] Examples 240 to 243 The compounds of Examples 240 to 243 shown in the table below were synthesized according to the method shown in Example 239. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0691] JPEG0007734129000219.jpg196170

[0692] Example 244 Synthesis of N-[1-(3-chloro-4-methoxybenzyl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0244] (hereinafter referred to as compound

[0244] )

[0693] TIFF0007734129000220.tif2055

[0694] To a solution of compound

[0142] (20 mg) in dichloromethane (0.5 mL), 60% sodium hydride (3.0 mg) and 3-chloro-4-methoxybenzaldehyde (20 mg) were added at room temperature, and the mixture was stirred at room temperature for 10 minutes. Sodium triacetoxyborohydride (34 mg) was then added at room temperature, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (4.9 mg) as a yellow solid. ESI-MS: 476.2 [M+H] +

[0695] Example 245 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]benzamide

[0245] (hereinafter referred to as compound

[0245] )

[0696] TIFF0007734129000221.tif2551

[0697] To a solution of compound

[0142] (21 mg) in DMF (0.5 mL), DIPEA (27 μL), 2-hydroxyisobutyric acid (7.5 mg), and (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (31 mg) were added at room temperature, and the mixture was stirred at room temperature for 17 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (8.2 mg) as a white solid. 1H-NMR(400MHz,DMSO-d6)δ:8.56(d,J=5.5Hz,1H),8.40(d,J=7.8Hz,1H),8. 21(d,J=2.3Hz,1H),8.06(d,J=8.7Hz,2H),8.02(d,J=8.2Hz,2H),7.69(d,J= 5.5Hz,1H),7.37-7.36(m,1H),5.35(s,1H),4.84-4.34(m,2H),4.12-4.04(m ,1H),3.20-2.66(m,2H),1.87-1.84(m,2H),1.52-1.44(m,2H),1.33(s,6H). ESI-MS: 408.2 [M+H] +

[0698] Example 246 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(3,3,3-trifluoropropanoyl)piperidin-4-yl]benzamide

[0246] (hereinafter referred to as compound

[0246] )

[0699] TIFF0007734129000222.tif2551

[0700] The title compound was synthesized by a method similar to Example 245, except that 3,3,3-trifluoropropionic acid was used instead of 2-hydroxyisobutyric acid. ESI-MS: 432.2 [M+H] +

[0701] Example 247 Synthesis of N-(1-cyanopiperidin-4-yl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0247] (hereinafter referred to as compound

[0247] )

[0702] TIFF0007734129000223.tif2552

[0703] To a solution of compound

[0142] (100 mg) in dichloromethane (1.0 mL), DIPEA (255 μL) and cyanogen bromide (379 mg) were added at room temperature, and the mixture was stirred at room temperature for 16 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (92 mg) as a yellow solid. ESI-MS: 347.1 [M+H] +

[0704] Example 248 Synthesis of N-[1-(1H-tetrazol-5-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0248] (hereinafter referred to as compound

[0248] )

[0705] TIFF0007734129000224.tif2546

[0706] To a solution of compound

[0247] (87 mg) in DMF (2.0 mL), sodium azide (253 mg) and triethylamine hydrochloride (253 mg) were added at room temperature, and the mixture was stirred at 100°C for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (21 mg) as a white solid. ESI-MS: 390.2 [M+H] +

[0707] Example 249 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2-methyl-2H-tetrazol-5-yl)piperidin-4-yl]benzamide

[0249] (hereinafter referred to as compound

[0249] )

[0708] TIFF0007734129000225.tif2548

[0709] To a solution of compound

[0248] (19 mg) in DMF (0.5 mL), potassium carbonate (20 mg) and methyl iodide (5.0 μL) were added at room temperature, and the mixture was stirred at 60° C. for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (11 mg) as a white solid. ESI-MS: 404.2 [M+H] +

[0710] Example 250 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-pyrazol-5-yl)piperidin-4-yl]benzamide

[0250] (hereinafter referred to as compound

[0250] )

[0711] TIFF0007734129000226.tif2549

[0712] (1) Synthesis of N-[1-(4-formyl-1-methyl-1H-pyrazol-5-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide [250-1] (hereinafter referred to as compound [250-1])

[0713] TIFF0007734129000227.tif3046

[0714] To a solution of compound

[0142] (14 mg) in DMSO (0.2 mL), DIPEA (12 μL), cesium carbonate (10 mg), and 5-chloro-1-methyl-1H-pyrazole-4-carbaldehyde (10 mg) were added at room temperature, and the mixture was stirred at 150° C. for 6 hours using a microwave reactor. Water was added to the reaction mixture, and the mixture was extracted with toluene. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (2.5 mg) as a brown oil. ESI-MS: 430.2 [M+H] +

[0715] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-pyrazol-5-yl)piperidin-4-yl]benzamide

[0250] To a solution of compound [250-1] (2.5 mg) in methanol (0.2 mL), p-toluenesulfonic acid monohydrate (0.1 mg) was added at room temperature and stirred at 120 °C for 20 minutes using a microwave reactor. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (2.0 mg) as a brown solid. ESI-MS: 402.2 [M+H] +

[0716] Example 251 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-imidazol-2-yl)piperidin-4-yl]benzamide

[0251] (hereinafter referred to as compound

[0251] )

[0717] TIFF0007734129000228.tif2547

[0718] (1) Synthesis of 4-azido-1-(1-methyl-1H-imidazol-2-yl)piperidine [251-1] (hereinafter referred to as compound [251-1])

[0719] TIFF0007734129000229.tif2029

[0720] To a solution of 1-(1-methyl-1H-imidazol-2-yl)piperidin-4-ol (16 mg) obtained by a literature method (WO 2011 / 143645) in dichloromethane (0.5 mL), triethylamine (23 μL) and methanesulfonyl chloride (33 μL) were added at room temperature, and the mixture was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture, which was then extracted with chloroform. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the resulting residue in DMF (0.3 mL) and THF (0.3 mL), sodium azide (28 mg) was added at room temperature, and the mixture was stirred at 100°C for 2 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (9.3 mg) as a yellow oil. ESI-MS: 207.2 [M+H] +

[0721] (2) Synthesis of 1-(1-methyl-1H-imidazol-2-yl)piperidin-4-amine [251-2] (hereinafter referred to as compound [251-2])

[0722] TIFF0007734129000230.tif2032

[0723] To a solution of compound [251-1] (9.3 mg) in ethanol (0.5 mL), 10% palladium on activated carbon (4.8 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 16 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (5.4 mg) as a colorless oil. 1 H-NMR(400MHz,CDCl3)δ:6.76(d,J=1.4Hz,1H),6.65(d,J=1.4Hz,1H),3.72(s,3H),3.2 3-3.20(m,2H),2.95-2.84(m,3H),2.68(br,2H),1.96-1.93(m,2H),1.62-1.54(m,2H).

[0724] (3) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-imidazol-2-yl)piperidin-4-yl]benzamide

[0251] The title compound was synthesized from the compound [251-2] according to the method of step (2) of Example 99. ESI-MS: 402.2 [M+H] +

[0725] Example 252 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-pyrazol-4-yl)piperidin-4-yl]benzamide

[0252] (hereinafter referred to as compound

[0252] )

[0726] TIFF0007734129000231.tif2548

[0727] To a solution of compound

[0142] (113 mg) in DMSO (0.9 mL), 4-iodo-1-methylpyrazole (30.0 mg), DIPEA (98.0 μL), L-proline (13.0 mg), potassium carbonate (100 mg), and copper(I) iodide (11.0 mg) were added at room temperature, and the mixture was stirred at 100°C under an argon atmosphere for 23 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (10.7 mg) as an orange solid. ESI-MS: 402.2 [M+H] +

[0728] Example 253 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{1-[4-(hydroxymethyl)-1-methyl-1H-imidazol-5-yl]piperidin-4-yl}benzamide

[0253] (hereinafter referred to as compound

[0253] )

[0729] TIFF0007734129000232.tif3053

[0730] (1) Synthesis of N-[1-(4-formyl-1-methyl-1H-imidazol-5-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide [253-1] (hereinafter referred to as compound [253-1])

[0731] TIFF0007734129000233.tif3054

[0732] The title compound was synthesized by a method similar to step (1) of Example 250, except that 5-chloro-1-methyl-1H-imidazole-4-carbaldehyde obtained by a method described in the literature (WO 2010 / 132999) was used instead of 5-chloro-1-methyl-1H-pyrazole-4-carbaldehyde. ESI-MS: 430.2 [M+H] +

[0733] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{1-[4-(hydroxymethyl)-1-methyl-1H-imidazol-5-yl]piperidin-4-yl}benzamide

[0253] To a solution of compound [253-1] (33 mg) in methanol (0.8 mL), sodium borohydride (12 mg) was added at room temperature and stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (13 mg) as a white solid. ESI-MS: 432.2 [M+H] +

[0734] Example 254 Synthesis of ethyl 2-{4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]piperidin-1-yl]oxazole-5-carboxylate

[0254] (hereinafter referred to as compound

[0254] )

[0735] TIFF0007734129000234.tif3661

[0736] To a solution of compound

[0142] (53 mg) in acetonitrile (0.65 mL), ethyl 2-chloro-1,3-oxazole-5-carboxylate (28 mg) and potassium carbonate (90 mg) were added at room temperature, and the mixture was stirred at 80°C for 22 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (42 mg) as a yellow solid. ESI-MS: 461.2 [M+H] +

[0737] Example 255 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(hydroxymethyl)oxazol-2-yl]piperidin-4-yl}benzamide

[0255] (hereinafter referred to as compound

[0255] )

[0738] TIFF0007734129000235.tif3652

[0739] To a solution of compound

[0254] (4.7 mg) in ethanol (0.3 mL), sodium borohydride (1.8 mg) and lithium chloride (2.2 mg) were added at room temperature, and the mixture was stirred at 70°C for 19 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (1.9 mg) as a white solid. ESI-MS: 419.2 [M+H] +

[0740] Example 256 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxycyclohexyl)benzamide

[0256] (hereinafter referred to as compound

[0256] )

[0741] TIFF0007734129000236.tif2552

[0742] To a solution of compound [99-1] (239 mg) in DMF (3.3 mL), DIPEA (680 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (471 mg), and trans-4-aminocyclohexanol (150 mg) were added at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (206 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.9Hz,1H),8.30(d,J=7.8Hz,1H),8.23( d,J=2.3Hz,1H),8.08(dd,J=6.9,1.8Hz,2H),8.00(dd,J=6.6,2.1Hz,2H),7.72( dd,J=5.7,1.1Hz,1H),7.37-7.36(m,1H),4.55(d,J=4.1Hz,1H),3.77-3.73(m,1 H),3.43-3.31(m,1H),1.87-1.82(m,4H),1.45-1.33(m,2H),1.30-1.19(m,2H). ESI-MS: 337.2 [M+H] +

[0743] Example 257 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(1-hydroxycyclopropyl)cyclohexyl]benzamide

[0257] (hereinafter referred to as compound

[0257] )

[0744] TIFF0007734129000237.tif2551

[0745] (1) Synthesis of trans-4-(dibenzylamino)cyclohexane-1-carboxylate methyl [257-1] (hereinafter referred to as compound [257-1])

[0746] TIFF0007734129000238.tif3041

[0747] To a solution of methyl trans-4-aminocyclohexanecarboxylate hydrochloride (387 mg) in acetonitrile (6.7 mL), potassium carbonate (1.11 g) and benzyl bromide (598 μL) were added at room temperature, and the mixture was stirred at 80° C. for 9 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by reverse-phase silica gel column chromatography to give the title compound (344 mg) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:7.36-7.35(m,4H),7.30-7.26(m,4H),7.22-7.18(m,2H),3.63- 3.62(m,7H),2.55-2.49(m,1H),2.23-2.17(m,1H),2.02-1.95(m,4H),1.43-1.30(m,4H). ESI-MS: 338.6 [M+H] +

[0748] (2) Synthesis of 1-[trans-4-(dibenzylamino)cyclohexyl]cyclopropan-1-ol [257-2] (hereinafter referred to as compound [257-2])

[0749] TIFF0007734129000239.tif2536

[0750] Under an argon atmosphere, titanium tetraisopropoxide (620 μL) was added to a solution of compound [257-1] (238 mg) in THF (23.5 mL) at room temperature. A 1 M THF solution (4.23 mL) of ethylmagnesium bromide was added dropwise to the reaction mixture over 5 minutes, followed by stirring at room temperature for 21 hours. Water was added to the reaction mixture, which was then 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 column chromatography to yield the title compound (186 mg) as a white solid. 1H-NMR(400MHz,CDCl3)δ:7.38-7.36(m,4H),7.30-7.26(m,4H),7.22-7.18(m,2H),3.62(s,4H),2.54-2.47(m,1H),1.99-1.95(m,2 H),1.83-1.80(m,2H),1.62(s,1H),1.42-1.32(m,2H),1.26-1.16(m,2H),0.93-0.85(m,1H),0.68-0.66(m,2H),0.42-0.39(m,2H). ESI-MS: 336.1 [M+H] +

[0751] (3) Synthesis of 1-(trans-4-aminocyclohexyl)cyclopropan-1-ol [257-3] (hereinafter referred to as compound [257-3])

[0752] TIFF0007734129000240.tif2036

[0753] To a solution of compound [257-2] (185 mg) in ethanol (6.9 mL), 20% palladium hydroxide on activated carbon (37.0 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 17 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (81.8 mg) as a white solid. 1 H-NMR(400MHz,CDCl3)δ:2.67-2.59(m,1H),1.94-1.90(m,2H),1.81-1.76(m,2H),1.41- 1.30(m,2H),1.13-1.03(m,2H),0.95-0.87(m,1H),0.72-0.69(m,2H),0.46-0.43(m,2H). ESI-MS: 156.3 [M+H] +

[0754] (4) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(1-hydroxycyclopropyl)cyclohexyl]benzamide

[0257] To a solution of compound [99-1] (59 mg) in DMF (0.82 mL), DIPEA (209 μL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (137 mg), and compound [257-3] (38 mg) were added at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (18 mg) as an orange solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.9Hz,1H),8.33(d,J=8.2Hz,1H),8.24(d, J=2.3Hz,1H),8.10-8.08(m,2H),8.01-7.99(m,2H),7.72(dd,J=5.5,0.9Hz,1H),7 .37-7.36(m,1H),4.87(s,1H),3.74-3.72(m,1H),1.93-1.88(m,2H),1.75-1.70(m ,2H),1.36-1.31(m,4H),0.94-0.89(m,1H),0.50-0.47(m,2H),0.36-0.33(m,2H). ESI-MS: 377.2 [M+H] +

[0755] Example 258 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide

[0258] (hereinafter referred to as compound

[0258] )

[0756] TIFF0007734129000241.tif2558

[0757] (1) Synthesis of 1-({[trans-4-(dibenzylamino)cyclohexyl]oxy}methyl)cyclopropan-1-ol [258-1] (hereinafter referred to as compound [258-1])

[0758] TIFF0007734129000242.tif2544

[0759] To a solution of compound [64-1] (398 mg) in THF (32 mL), titanium tetraisopropoxide (852 μL) and a 1 M THF solution of ethylmagnesium bromide (5.82 mL) were added at room temperature, and the mixture was stirred at room temperature for 13 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (45.0 mg) as a white solid. ESI-MS: 366.3 [M+H] +

[0760] (2) Synthesis of 1-{[(trans-4-aminocyclohexyl)oxy]methyl}cyclopropan-1-ol [258-2] (hereinafter referred to as compound [258-2])

[0761] TIFF0007734129000243.tif2046

[0762] To a solution of compound [258-1] (45 mg) in ethanol (0.5 mL), 20% palladium hydroxide on activated carbon (20 mg) was added at room temperature, and the mixture was stirred under a hydrogen atmosphere at room temperature for 18 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give the title compound (25 mg) as a colorless oil. 1 H-NMR(400MHz,CD3OD)δ:3.51(s,2H),3.39-3.32(m,1H),2.77-2.72(m,1H),2.09-2.0 6(m,2H),1.94-1.91(m,2H),1.33-1.21(m,4H),0.71-0.68(m,2H),0.57-0.50(m,2H). ESI-MS: 186.2 [M+H] +

[0763] (3) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide

[0258] To a solution of compound [99-1] (13 mg) in DMF (0.5 mL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (23 mg), DIPEA (9.1 μL), and compound [258-2] (9.0 mg) were added at room temperature, and the mixture was stirred at room temperature for 19 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 successively 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 column chromatography to obtain the title compound (6.2 mg) as a white solid. 1 H-NMR(400MHz,CD3OD)δ:8.53(d,J=5.9Hz,1H),7.99-7.98(m,5H),7.63(d,J=5.5Hz,1H),7.19(d,J=1.1Hz,1H),3.94-3.88(m,1H) ),3.54(s,2H),3.47-3.43(m,1H),2.17-2.14(m,2H),2.07-2.04(m,2H),1.52-1.35(m,4H),0.71-0.68(m,2H),0.59-0.56(m,2H). ESI-MS: 407.3 [M+H] +

[0764] Example 259 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxy-4-methylcyclohexyl)benzamide

[0259] (hereinafter referred to as compound

[0259] )

[0765] TIFF0007734129000244.tif2547

[0766] To a solution of compound [99-1] (50 mg) in DMF (1.0 mL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (116 mg), DIPEA (142 μL), and trans-4-amino-1-methylcyclohexanol (35 mg) were added at room temperature, and the mixture was stirred at room temperature for 22 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (30 mg) as a reddish-brown solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.59(d,J=5.5Hz,1H),8.28(d,J=7.8Hz,1H),8.24(d,J=2.3Hz,1H),8.08(d,J=8.2Hz,2H),8.00(d,J=8.2Hz,2H), 7.73-7.71(m,1H),7.37-7.36(m,1H),4.29(br,1H),3.87-3.79(m,1H) ,1.78-1.75(m,2H),1.62-1.58(m,2H),1.54-1.41(m,4H),1.16(s,3H). ESI-MS: 351.2 [M+H] +

[0767] Example 260 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)benzamide

[0260] (hereinafter referred to as compound

[0260] )

[0768] TIFF0007734129000245.tif2552

[0769] To a solution of compound [99-1] (30 mg) in DMF (1.0 mL), (1-cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (160 mg), DIPEA (64 μL), and 4-aminobicyclo[2.2.2]octan-1-ol hydrochloride (49 mg) were added at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (31 mg) as a yellow solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.9Hz,1H),8.24(d,J=2.3Hz,1H),8.04(d,J=8.2Hz,2H),7.92(d, J=8.2Hz,2H),7.74-7.72(m,2H),7.34-7.33(m,1H),3.51(br,1H),2.07-2.03(m,6H),1.64-1.60(m,6H). ESI-MS: 363.2 [M+H] +

[0770] Examples 261 to 285 The compounds of Examples 261 to 285 shown in the table below were synthesized according to the method of Example 260. The structure, name and ESI-MS of the compound of each Example are shown in the table below.

[0771] TIFF0007734129000246.tif237170

[0772] TIFF0007734129000247.tif231170

[0773] TIFF0007734129000248.tif252170

[0774] TIFF0007734129000249.tif231170

[0775] TIFF0007734129000250.tif231170

[0776] Example 286 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(methoxy-d3)cyclohexyl]benzamide

[0286] (hereinafter referred to as compound

[0286] )

[0777] TIFF0007734129000251.tif2557

[0778] (1) Synthesis of trans-N,N-dibenzyl-4-(methoxy-d3)cyclohexane-1-amine [286-1] (hereinafter referred to as compound [286-1])

[0779] TIFF0007734129000252.tif2541

[0780] To a solution of compound [64-1] (200 mg) in THF (3.4 mL), 60% sodium hydride (82 mg) and methyl iodide-d3 (60 μL) were added at 0 °C, and the mixture was stirred for 1 h at room temperature. The mixture was stirred for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was 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 column chromatography to yield the title compound (199 mg) as a colorless oil. 1 H-NMR(400MHz,CDCl3)δ:7.37-7.18(m,10H),3.61(s,4H),3.10-3.00(m,1H),2.58-2. 47(m,1H),2.09-2.03(m,2H),1.96-1.90(m,2H),1.41-1.37(m,2H),1.13-1.02(m,2H). ESI-MS: 313.3 [M+H] +

[0781] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(methoxy-d3)cyclohexyl]benzamide

[0286] The title compound was synthesized from the compound [286-1] according to the methods of steps (3) and (4) of Example 257. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(d,J=5.7Hz,1H),8.34(d,J=7.8Hz,1H),8.2 4(d,J=2.3Hz,1H),8.08(dd,J=6.4,1.8Hz,2H),8.00(dd,J=6.9,1.8Hz,2H),7 .72(d,J=5.5Hz,1H),7.36-7.35(m,1H),3.82-3.76(m,1H),3.13-3.03(m,1H) ,2.07-2.02(m,2H),1.90-1.86(m,2H),1.45-1.32(m,2H),1.26-1.19(m,2H). ESI-MS: 354.2 [M+H] +

[0782] Example 287 Synthesis of N-(trans-4-ethoxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0287] (hereinafter referred to as compound

[0287] )

[0783] TIFF0007734129000253.tif2556

[0784] (1) Synthesis of trans-N,N-dibenzyl-4-ethoxycyclohexane-1-amine [287-1] (hereinafter referred to as compound [287-1])

[0785] TIFF0007734129000254.tif2540

[0786] The title compound was synthesized according to the method of Step (1) of Example 286, except that ethyl iodide was used instead of methyl iodide-d3. ESI-MS: 324.3 [M+H]+

[0787] (2) Synthesis of N-(trans-4-ethoxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0287] The title compound was synthesized from the compound [287-1] according to the methods of steps (3) and (4) of Example 257. ESI-MS: 365.2 [M+H] +

[0788] Example 288 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-isopropoxycyclohexyl)benzamide

[0288] (hereinafter referred to as compound

[0288] )

[0789] TIFF0007734129000255.tif2556

[0790] (1) Synthesis of trans-N,N-dibenzyl-4-isopropoxycyclohexane-1-amine [288-1] (hereinafter referred to as compound [288-1])

[0791] TIFF0007734129000256.tif2540

[0792] The title compound was synthesized according to the method of Step (1) of Example 286, except that isopropyl iodide was used instead of methyl iodide-d3. ESI-MS: 338.3 [M+H] +

[0793] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-isopropoxycyclohexyl)benzamide

[0288] The title compound was synthesized from the compound [288-1] according to the methods of steps (3) and (4) of Example 257. 1H-NMR(400MHz,CD3OD)δ:8.51(d,J=5.9Hz,1H),8.00-7.99(m,5H),7.61(dd,J=5.9,0.9Hz,1H),7.18(d,J=0.9Hz,1H), 3.93-3.86(m,1H),3.82-3.76(m,1H),3.40-3.38(m,1H),2.06-2.04(m,4H),1.65-1.52(m,4H),1.13(d,J=5.9Hz,6H). ESI-MS: 379.3 [M+H] +

[0794] Example 289 Synthesis of N-(trans-4-ethyl-4-hydroxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0289] (hereinafter referred to as compound

[0289] )

[0795] TIFF0007734129000257.tif2545

[0796] (1) Synthesis of trans-4-(dibenzylamino)-1-ethylcyclohexan-1-ol [289-1-a] (hereinafter referred to as compound [289-1-a]) and cis-4-(dibenzylamino)-1-ethylcyclohexan-1-ol [289-1-b] (hereinafter referred to as compound [289-1-b])

[0797] TIFF0007734129000258.tif2567

[0798] To a solution of 4-(dibenzylamino)cyclohexanone (1.0 g) in toluene (15 mL), a 1.1 M solution of triethylaluminum in toluene (6.8 mL) was added at room temperature, and the mixture was stirred at room temperature for 16 hours. A 2 M aqueous solution of sodium hydroxide (4.5 mL) was added dropwise to the reaction mixture, which was then 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 column chromatography to give the title compound [289-1-a] (96 mg) and the title compound [289-1-b] (102 mg), each as a white solid. Compound [289-1-a] 1 H-NMR(400MHz,CDCl3)δ:7.35-7.17(m,10H),3.63(s,4H),2.57-2.53(m,1H),1.77-1.75( m,4H),1.54(q,J=7.5Hz,2H),1.47-1.37(m,2H),1.31-1.23(m,2H),0.87(t,J=7.5Hz,3H). ESI-MS: 324.2 [M+H] + Compound [289-1-b] 1 H-NMR(400MHz,CDCl3)δ:7.38-7.18(m,10H),3.66(s,4H),2.48-2.44(m,1H),1. 80-1.58(m,6H),1.39(q,J=7.5Hz,2H),1.28-1.18(m,2H),0.86(t,J=7.5Hz,3H). ESI-MS: 324.2 [M+H] +

[0799] (2) Synthesis of N-(trans-4-ethyl-4-hydroxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0289] The title compound was synthesized from the compound [289-1-a] according to the methods of steps (3) and (4) of Example 257. ESI-MS: 365.2 [M+H] +

[0800] Example 290 Synthesis of N-(cis-4-ethyl-4-hydroxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0290] (hereinafter referred to as compound

[0290] )

[0801] TIFF0007734129000259.tif2547

[0802] The title compound was synthesized from the compound [289-1-b] according to the methods of steps (3) and (4) of Example 257. ESI-MS: 365.2 [M+H] +

[0803] Example 291 Synthesis of N-(cis-4-cyclopropyl-4-hydroxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0291] (hereinafter referred to as compound

[0291] )

[0804] TIFF0007734129000260.tif2549

[0805] (1) Synthesis of cis-1-cyclopropyl-4-(dibenzylamino)cyclohexan-1-ol [291-1] (hereinafter referred to as compound [291-1])

[0806] TIFF0007734129000261.tif2534

[0807] To a solution of 4-(dibenzylamino)cyclohexanone (500 mg) in THF (57 mL), a 0.7 M THF solution of cyclopropylmagnesium bromide (14.6 mL) was added at room temperature, and the mixture was stirred at room temperature for 4 hours. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, which was then 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 column chromatography to give the title compound (104 mg) as a white solid. ESI-MS: 336.2 [M+H] +

[0808] (2) Synthesis of N-(cis-4-cyclopropyl-4-hydroxycyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0291] The title compound was synthesized from the compound [291-1] according to the methods of steps (3) and (4) of Example 257. ESI-MS: 377.3 [M+H] +

[0809] Example 292 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(cis-4-hydroxy-4-isopropylcyclohexyl)benzamide

[0292] (hereinafter referred to as compound

[0292] )

[0810] TIFF0007734129000262.tif2546

[0811] (1) Synthesis of cis-4-(dibenzylamino)-1-isopropylcyclohexan-1-ol [292-1] (hereinafter referred to as compound [292-1])

[0812] TIFF0007734129000263.tif2532

[0813] The title compound was synthesized by a method similar to that of Step (1) of Example 291, except that a 2 M solution of isopropylmagnesium chloride in THF was used instead of a 0.7 M solution of cyclopropylmagnesium bromide in THF. ESI-MS: 338.3 [M+H] +

[0814] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(cis-4-hydroxy-4-isopropylcyclohexyl)benzamide

[0292] The title compound was synthesized from the compound [292-1] according to the methods of steps (3) and (4) of Example 257. ESI-MS: 379.3 [M+H] +

[0815] Example 293 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(cis-4-hydroxycycloheptyl)benzamide

[0293] (hereinafter referred to as compound

[0293] )

[0816] TIFF0007734129000264.tif2543

[0817] (1) Synthesis of cis-4-aminocycloheptan-1-ol hydrochloride [293-1] (hereinafter referred to as compound [293-1])

[0818] TIFF0007734129000265.tif2027

[0819] To a solution of tert-butyl N-(4-oxocycloheptyl)carbamate (120 mg) in methanol (5.4 mL) was added sodium borohydride (31 mg) at room temperature, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. A 4 M solution of hydrogen chloride in ethyl acetate (2.0 mL) was added to the resulting residue at room temperature, and the mixture was stirred for 4 hours. The reaction mixture was concentrated under reduced pressure to give the title compound (85 mg) as a yellow oil. ESI-MS: 130.2 [M+H] +

[0820] (2) Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(cis-4-hydroxycycloheptyl)benzamide

[0293] The title compound was synthesized from the compound [293-1] according to the method of Example 190. ESI-MS: 351.2 [M+H] +

[0821] Example 294 Synthesis of N-{trans-4-[(2,2-difluoroethyl)amino]cyclohexyl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0294] (hereinafter referred to as compound

[0294] )

[0822] TIFF0007734129000266.tif2552

[0823] (1) Synthesis of N-(trans-4-aminocyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide [294-1] (hereinafter referred to as compound [294-1])

[0824] TIFF0007734129000267.tif2554

[0825] To a solution of compound [99-1] (50 mg) in methanol (2.0 mL) / toluene (1.0 mL), 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (290 mg) and trans-1,4-cyclohexanediamine (150 mg) were added at room temperature, and the mixture was stirred at 110°C for 17 hours. The reaction mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (30 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.55(d,J=5.5Hz,1H),8.29-8.28(m,1H),8.21(d,J=2.3Hz,1H),8.04(d,J=8.2Hz,2H),7.97(d,J=8.2Hz,2H),7.69(d ,J=5.5Hz,1H),7.33-7.32(m,1H),3.72-3.69(m,1H),3.28(br,2H),2.5 5-2.45(m,1H),1.81-1.77(m,4H),1.41-1.32(m,2H),1.18-1.12(m,2H). ESI-MS: 336.2 [M+H] +

[0826] (2) Synthesis of N-{trans-4-[(2,2-difluoroethyl)amino]cyclohexyl}-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0294] To a solution of compound [294-1] (14 mg) in 1,4-dioxane (0.5 mL), DIPEA (15 μL) and 2,2-difluoroethyl trifluoromethanesulfonate (40 μL) were added at room temperature, and the mixture was stirred at room temperature for 17 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (8.2 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.56(d,J=5.9Hz,1H),8.32(d,J=7.8Hz,1H),8.21(d ,J=1.8Hz,1H),8.06(d,J=8.2Hz,2H),7.98(d,J=8.2Hz,2H),7.70(d,J=5.5Hz,1 H),7.37-7.36(m,1H),5.96(t,J=63.0Hz,1H),3.80-3.70(m,1H),3.10-2.85(m, 2H),2.44-2.38(m,1H),1.97-1.83(m,5H),1.40-1.31(m,2H),1.15-1.10(m,2H). ESI-MS: 400.3 [M+H] +

[0827] Example 295 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(oxetan-3-ylamino)cyclohexyl]benzamide

[0295] (hereinafter referred to as compound

[0295] )

[0828] TIFF0007734129000268.tif2552

[0829] To a solution of compound [294-1] (53 mg) in dichloromethane (1.6 mL) / DMF (1.0 mL), sodium acetate (54 mg), 3-oxetanone (16 mg), and sodium cyanoborohydride (50 mg) were added at room temperature, and the mixture was stirred at 80°C for 16 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (22 mg) as a white solid. 1 H-NMR(400MHz,DMSO-d6)δ:8.58(dd,J=5.7,2.1Hz,1H),8.32(d,J=6.9Hz,1H),8.23(d,J=2.3H) z,1H),8.08(d,J=6.4Hz,2H),8.00(d,J=6.4Hz,2H),7.72(d,J=5.9Hz,1H),7.37-7.36(m,1H),4 .62(dd,J=6.2,5.9Hz,2H),4.30(dd,J=6.2,5.9Hz,2H),3.97-3.94(m,1H),3.76-3.68(m,1H), 3.46-3.40(m,1H),2.40-2.36(m,1H),1.89-1.75(m,4H),1.40-1.31(m,2H),1.15-1.06(m,2H). ESI-MS: 392.2 [M+H] +

[0830] Example 296 Synthesis of N-(trans-4-acetamidocyclohexyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide

[0296] (hereinafter referred to as compound

[0296] )

[0831] TIFF0007734129000269.tif2550

[0832] To a solution of compound [294-1] (10 mg) in ethyl acetate (0.5 mL), acetic anhydride (36 μL) and DIPEA (65 μL) were added at room temperature, and the mixture was stirred at room temperature for 90 minutes. Water was added to the reaction mixture, and the mixture was 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 column chromatography to obtain the title compound (5.4 mg) as a white solid. ESI-MS: 378.2 [M+H] +

[0833] Example 297 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(5-methyl-1H-tetrazol-1-yl)cyclohexyl]benzamide

[0297] (hereinafter referred to as compound

[0297] )

[0834] TIFF0007734129000270.tif2546

[0835] To a solution of compound

[0296] (10 mg) in pyridine (0.2 mL), diphenylphosphoryl azide (72 μL) was added at room temperature, and the mixture was stirred at 115° C. for 6 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (5.0 mg) as a yellow solid. ESI-MS: 403.2 [M+H] +

[0836] Example 298 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-propionamidocyclohexyl)benzamide

[0298] (hereinafter referred to as compound

[0298] )

[0837] TIFF0007734129000271.tif2549

[0838] To a solution of compound [294-1] (20 mg) in THF (0.6 mL), pyridine (16 μL) and propionyl chloride (6.8 μL) were added at 0° C. and stirred at room temperature for 24 hours. Water was added to the reaction mixture, which was then 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 column chromatography to give the title compound (5.2 mg) as a white solid. ESI-MS: 392.2 [M+H] +

[0839] Example 299 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-oxopyrrolidin-1-yl)cyclohexyl]benzamide

[0299] (hereinafter referred to as compound

[0299] )

[0840] TIFF0007734129000272.tif2548

[0841] To a solution of compound [294-1] (67 mg) in 1,4-dioxane (0.7 mL), 60% sodium hydride (21 mg) and 4-chlorobutyryl chloride (34 μL) were added at room temperature, and the mixture was stirred at 80° C. for 48 hours. Water was added to the reaction mixture, and the mixture was 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 column chromatography to give the title compound (15 mg) as a white solid. ESI-MS: 404.3 [M+H] +

[0842] Example 300 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-oxopiperidin-1-yl)cyclohexyl]benzamide

[0300] (hereinafter referred to as compound

[0300] )

[0843] TIFF0007734129000273.tif2546

[0844] The title compound was synthesized by a method similar to Example 299, except that 5-chloropentanoyl chloride was used instead of 4-chlorobutyryl chloride. ESI-MS: 418.3 [M+H] +

[0845] Example 301 Synthesis of 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(2-methoxyethyl)amino]cyclohexyl}benzamide

[0301] (hereinafter ...

Claims

1. Formula (I): [In formula (I), R 1 is a hydrogen atom or C 1-6 represents an alkyl group; R 2 is a hydrogen atom or C 1-6 represents an alkyl group; R 3 represents a hydrogen atom, a halogen atom, a cyano group, an amino group, a carbamoyl group, C 1-6 Alkyl group, C 2-6 Alkenyl group, or hydroxy C 1-6 represents an alkyl group; R 4 represents a hydrogen atom, a halogen atom, a cyano group, a carbamoyl group, C 1-6 Alkyl group, C 2-6 Alkenyl group, or hydroxy C 1-6 represents an alkyl group; R 5 is a hydrogen atom, a halogen atom, a cyano group, a hydroxy group, or C 1-6 represents an alkyl group; W is an oxygen atom, a sulfur atom, or a group represented by the general formula: -N(R 6 )- represents a group represented by; R 6 is a hydrogen atom or C 1-6 represents an alkyl group; X is C 1-6 Alkyl group, C 2-6 Alkenyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 alkyl group, (C 1-6 Alkoxy)C 1-6 Alkyl group, (haloC 1-6 Alkoxy)C 1-6 Alkyl group, amino C 1-6 Alkyl group, (mono C 1-6 alkylamino)C 1-6 Alkyl group, (diC 1-6 alkylamino)C 1-6 Alkyl group, carbamoyl C 1-6 Alkyl group, (mono C 1-6 alkylcarbamoyl)C 1-6 Alkyl group, (diC 1-6 alkylcarbamoyl)C 1-6 Alkyl group, sulfamoyl C 1-6 Alkyl group, (mono C 1-6 alkylsulfamoyl)C 1-6 Alkyl group, (diC 1-6 alkylsulfamoyl)C 1-6 an alkyl group, or General formula (II): (In the formula, The wavy line represents the point of attachment to the nitrogen atom; L 1 is a single bond, C 1-6 Alkanediyl group or hydroxy C 1-6 represents an alkanediyl group; Ring Y is C 6-10 Aryl group, heteroaryl group, C 3-10 represents a cycloalkyl group or a 4- to 10-membered heterocyclyl group (wherein 3-10 The cycloalkyl group and the 4- to 10-membered heterocyclyl group may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may form a bicyclo or spiro ring group; R 7 each independently represents a halogen atom, a cyano group, a hydroxy group, a sulfanyl group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, a formyl group, an imino group, an azido group, a hydrazino group, a nitro group, an oxetanylamino group, C 1-6 Alkyl group, C 2-6 Alkenyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 Alkyl group, hydroxyhalo C 1-6 alkyl group, (C 1-6 Alkoxy)C 1-6 Alkyl group, C 2-7 Alkanoyl group, halo C 2-7 Alkanoyl group, hydroxy C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, halo C 1-6 Alkoxy group, hydroxy C 1-6 Alkoxy group, C 1-6 Alkylthio group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, mono(haloC 1-6 alkyl)amino group, C 2-7 Alkoxycarbonyl group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl) C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkyl sulfonyl amino group, mono(C 2-7 alkoxycarbonyl)amino group, C 3-6 Cycloalkyl group, hydroxy C 3-6 Cycloalkyl groups, (hydroxy C 3-6 Cycloalkyl)C 1-6 Alkoxy group, C 3-6 represents a cycloalkylcarbonyl group, a cyclic ether group, a cyclic amino group, a halocyclic amino group, or an oxo group; L 2 is a single bond, C 1-6 Alkanediyl group, hydroxy C 1-6 represents an alkanediyl group, a carbonyl group, or a sulfonyl group; Ring Z represents a phenyl group, a heteroaryl group, or a 4- to 10-membered heterocyclyl group (the 4- to 10-membered heterocyclyl group may be fused with a benzene ring or a heteroaryl ring to form a fused ring group, or may form a bicyclo ring group or a spiro ring group); R 8 are each independently a halogen atom, a cyano group, a hydroxy group, a sulfanyl group, an amino group, a carbamoyl group, a sulfamoyl group, a carboxy group, a morpholinocarbonyl group, C 1-6 Alkyl group, C 2-6 Alkenyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 alkyl group, (C 1-6 Alkoxy)C 1-6 Alkyl group, C 2-7 Alkanoyl group, C 1-6 Alkylsulfonyl group, C 1-6 Alkoxy group, halo C 1-6 Alkoxy group, mono C 1-6 Alkylamino group, diC 1-6 Alkylamino group, C 2-7 Alkoxycarbonyl group, mono C 1-6 Alkylcarbamoyl group, diC 1-6 Alkylcarbamoyl group, C 1-6 Alkyl sulfonyloxy group, halo C 1-6 Alkylsulfonyloxy group, mono C 1-6 Alkyl sulfamoyl group, diC 1-6 Alkylsulfamoyl group, mono C 2-7 Alkanoylamino group, (C 2-7 Alkanoyl) C 1-6 Alkylamino group, diC 2-7 Alkanoylamino group, mono C 1-6 Alkyl sulfonyl amino group, mono(C 2-7 alkoxycarbonyl)amino group, C 3-6 represents a cycloalkyl group, a cyclic ether group, a cyclic amino group, a halocyclic amino group, or an oxo group; m represents 0, 1, 2 or 3; n represents 0, 1, or 2; and p represents 0 or 1. or a pharmaceutically acceptable salt thereof.

2. X is a compound represented by general formula (II): (In the formula, The wavy line represents the point of attachment to the nitrogen atom, L 1 , ring Y, R 7 , L 2 , ring Z, R 8 2. The compound according to claim 1, wherein m, n and p are as defined above, or a pharmaceutically acceptable salt thereof.

3. L 1 3. The compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof, wherein is a single bond or a methylene group.

4. 4. The compound according to claim 1, wherein p is 1, or a pharmaceutically acceptable salt thereof.

5. Ring Y is represented by the general formula (III): (In the formula, The wavy line is L 1 represents the point of attachment to * is L 2 represents the point of attachment to R 7 and m are as defined above; The compound according to claim 4, wherein ring A is a 4- to 10-membered nitrogen-containing heterocyclyl group, or a pharmaceutically acceptable salt thereof.

6. Ring Y is a group represented by the general formula: (In the formula, The wavy line is L 1 represents the point of attachment to * is L 2 represents the point of attachment to R 7 and m has the same meaning as defined above), or a pharmaceutically acceptable salt thereof.

7. 7. The compound according to any one of claims 4 to 6, wherein m is 0, or a pharmaceutically acceptable salt thereof.

8. L 2 The compound according to any one of claims 4 to 7, or a pharmaceutically acceptable salt thereof, wherein is a single bond.

9. 9. The compound according to any one of claims 4 to 8, or a pharmaceutically acceptable salt thereof, wherein ring Z is a phenyl group or a heteroaryl group.

10. 10. The compound according to any one of claims 4 to 9, or a pharmaceutically acceptable salt thereof, wherein ring Z is a phenyl group or a 5- or 6-membered nitrogen-containing heteroaryl group.

11. Ring Z is a group represented by the general formula: (In the formula, The wavy line is L 2 represents the point of attachment to R 8 and n is as defined above, R 9 is C 1-6 Alkyl group, halo C 1-6 Alkyl group, hydroxy C 1-6 alkyl group, (C 1-6 Alkoxy)C 1-6 Alkyl group or C 3-6 11. The compound according to claim 4, wherein R is a cycloalkyl group, or a pharmaceutically acceptable salt thereof.

12. 4. The compound according to claim 1, wherein p is 0, or a pharmaceutically acceptable salt thereof.

13. Ring Y is C 3-10 Cycloalkyl group (the above C 3-10 13. The compound according to claim 12, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group is optionally fused with a benzene ring or a heteroaryl ring to form a fused ring group, or optionally a bicyclo ring group or a spiro ring group, or a 4- to 10-membered heterocyclyl group (the 4- to 10-membered heterocyclyl group is optionally fused with a benzene ring or a heteroaryl ring to form a fused ring group, or optionally a bicyclo ring group or a spiro ring group).

14. Ring Y is C 3-10 Cycloalkyl group (the above C 3-10 14. The compound according to claim 12 or 13, or a pharmaceutically acceptable salt thereof, wherein the cycloalkyl group is optionally fused with a benzene ring or a heteroaryl ring to form a fused ring group, or optionally forms a bicyclo ring group or a spiro ring group.

15. Ring Y is a group represented by the general formula: (In the formula, The wavy line is L 1 represents the point of attachment to R 7 and m has the same meaning as defined above), or a pharmaceutically acceptable salt thereof.

16. Ring Y is a group represented by the general formula: (In the formula, The wavy line is L 1 represents the point of attachment to R 7 and m has the same meaning as defined above), or a pharmaceutically acceptable salt thereof.

17. Ring Y is a group represented by the general formula: (In the formula, The wavy line is L 1 represents the point of attachment to R 7 17. The compound according to claim 12, wherein R is a group represented by the formula: R is as defined above, or a pharmaceutically acceptable salt thereof.

18. 17. The compound according to any one of claims 12 to 16, or a pharmaceutically acceptable salt thereof, wherein m is 1 or 2.

19. W is an oxygen atom or a group represented by the general formula: -N(R 6 )-(wherein, R 6 19. The compound according to any one of claims 1 to 18, wherein R is a group represented by the formula: R is as defined above, or a pharmaceutically acceptable salt thereof.

20. 20. The compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein W is an oxygen atom.

21. W is a group represented by the general formula: -N(R 6 )-(wherein, R 6 The compound according to any one of claims 1 to 19, wherein R is a group represented by the formula (I) or (II), or a pharmaceutically acceptable salt thereof.

22. 20. The compound of any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof, wherein W is -NH-.

23. R 5 23. The compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof, wherein is a hydrogen atom or a fluorine atom.

24. R 1 and R2 are each independently a hydrogen atom or C 1-6 is an alkyl group, 24. The compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof, wherein R 4 is a hydrogen atom, a halogen atom, or a C 1-6 alkyl group.

25. R 3 is a hydrogen atom, a halogen atom, or C 1-6 Alkyl group or hydroxy group 1-6 25. The compound of any one of claims 1 to 24, or a pharmaceutically acceptable salt thereof, which is an alkyl group.

26. The following (1) to (49): (1) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (2) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(thieno[3,2-c]pyridin-4-yl)benzamide; (3) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide; (4) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(1-methyl-1H-tetrazol-5-yl)piperidin-4-yl]benzamide; (5) 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(2,2,2-trifluoroethyl)amino]cyclohexyl}benzamide; (6) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (7) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (8) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (9) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-methylfuro[3,2-c]pyridin-4-yl)benzamide; (10) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)piperidin-4-yl]benzamide; (11) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]benzamide; (12) (S)-4-(furo[3,2-c]pyridin-4-yl)-N-[1-(pyrimidin-2-yl)pyrrolidin-3-yl]benzamide; (13) (S)-4-(furo[3,2-c]pyridin-4-yl)-N-{1-[5-(hydroxymethyl)pyrimidin-2-yl]pyrrolidin-3-yl}benzamide; (14) N-(chroman-3-ylmethyl)-4-(furo[3,2-c]pyridin-4-yl)benzamide; (15) 4-(furo[3,2-c]pyridin-4-yl)-N-(1-propionylpiperidin-4-yl)benzamide; (16) N-[1-(cyclopropanecarbonyl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide; (17) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(oxetan-3-yl)piperidin-4-yl]benzamide; (18) N-[1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl]-4-(furo[3,2-c]pyridin-4-yl)benzamide; (19) 4-(furo[3,2-c]pyridin-4-yl)-N-[1-(2-hydroxy-2-methylpropanoyl)piperidin-4-yl]benzamide; (20) 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxycyclohexyl)benzamide; (21) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(1-hydroxycyclopropyl)cyclohexyl]benzamide; (22) 4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide; (23) 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxy-4-methylcyclohexyl)benzamide; (24) 4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)benzamide; (25) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(methoxy-d 3 ) cyclohexyl]benzamide; (26) 4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-isopropoxycyclohexyl)benzamide; (27) N-{trans-4-[(2,2-difluoroethyl)amino]cyclohexyl}-4-(furo[3,2-c]pyridin-4-yl)benzamide; (28) 4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(oxetan-3-ylamino)cyclohexyl]benzamide; (29) 4-[6-(hydroxymethyl)furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (30) 4-[6-(hydroxymethyl-d 2 ) furo[3,2-c]pyridin-4-yl]-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide; (31) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide; (32) N-[trans-4-(1-hydroxycyclopropyl)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (33) N-[1-(pyrimidin-2-yl)piperidin-4-yl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (34) N-(trans-4-hydroxycyclohexyl)-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (35) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(6-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (36) N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(7-methyl-1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (37) 3-fluoro-N-[trans-4-(2-hydroxypropan-2-yl)cyclohexyl]-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide; (38) N-[trans-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (39) N-(4-hydroxybicyclo[2.2.2]octan-1-yl)-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (40) N-(trans-4-hydroxy-4-methylcyclohexyl)-4-(6-methylfuro[3,2-c]pyridin-4-yl)benzamide; (41) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.2]octan-1-yl)benzamide; (42) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-(trans-4-hydroxy-4-methylcyclohexyl)benzamide; (43) 3-fluoro-4-(furo[3,2-c]pyridin-4-yl)-N-{trans-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide; (44) 4-(furo[3,2-c]pyridin-4-yl)-N-[cis-4-(2-hydroxy-2-methylpropoxy)cyclohexyl]benzamide; (45) 4-(furo[3,2-c]pyridin-4-yl)-N-(4-hydroxybicyclo[2.2.1]heptan-1-yl)benzamide; (46) N-(4-cyanobicyclo[2.2.2]octan-1-yl)-4-(furo[3,2-c]pyridin-4-yl)benzamide; (47) 4-[4-(furo[3,2-c]pyridin-4-yl)benzamido]bicyclo[2.2.2]octane-1-carboxamide; (48) 4-(furo[3,2-c]pyridin-4-yl)-N-{cis-4-[(1-hydroxycyclopropyl)methoxy]cyclohexyl}benzamide; and (49) 4-(furo[3,2-c]pyridin-4-yl)-N-[cis-4-(2-hydroxypropan-2-yl)cyclohexyl]benzamide 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from:

27. N-(2-acetamidoethyl)-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide, or N-(4-acetamidobutyl)-4-(1H-pyrrolo[3,2-c]pyridin-4-yl)benzamide or a pharmaceutically acceptable salt thereof, selected from:

28. 28. A pharmaceutical composition comprising a compound according to any one of claims 1 to 27 or a pharmaceutically acceptable salt thereof.

29. 28. A pharmaceutical composition for preventing or treating a disease associated with H-PGDS, comprising the compound according to any one of claims 1 to 27 or a pharmaceutically acceptable salt thereof.

30. 30. The pharmaceutical composition according to claim 29, wherein the disease associated with H-PGDS is selected from the group consisting of asthma, chronic obstructive pulmonary disease, allergic rhinitis, sinusitis, eosinophilic pneumonia, atherosclerosis, rheumatoid arthritis, cystic fibrosis, actinic keratosis, chronic urticaria, dermatitis, muscular dystrophy, sarcopenia, disuse muscle atrophy, muscle injury, wound, dermatomyositis, amyotrophic lateral sclerosis, cerebral infarction, myocardial infarction, ischemic bowel disease, ischemic kidney disease, ischemic gastric disease, ischemic liver disease, diabetic limb ischemia, and Buerger's disease.

31. 28. An H-PGDS inhibitor comprising the compound according to any one of claims 1 to 27 or a pharmaceutically acceptable salt thereof.

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