A pharmaceutical product containing a urea compound that antagonizes the LPA1 receptor as an active ingredient.

Abstract

To provide pharmaceuticals containing as an active ingredient a compound having an action to antagonize the LPA1 receptor, a pharmaceutically acceptable salt thereof, or a hydrate thereof.SOLUTION: Provided is a pharmaceutical containing as an active ingredient a compound represented by the following formula [I], a pharmaceutically acceptable salt thereof, or a hydrate thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a pharmaceutical product containing an LPA1 receptor antagonist as an active ingredient. More specifically, it relates to a pharmaceutical product containing a urea compound, which is an LPA1 receptor antagonist, as an active ingredient. [Background technology]

[0002] Lysophosphatidic acid (LPA) is a physiologically active phospholipid in which a fatty acid is attached to the 1st or 2nd position of a glycerol skeleton and a phosphate group is attached to the 3rd position. It includes 1-acyl LPA, 1-alkyl LPA, 2-acyl LPA, etc. It also exhibits diversity depending on the type of fatty acid attached, and there are many LPA subtypes that exhibit various chemical and physiological properties depending on the carbon chain length and degree of unsaturation of the fatty acid.

[0003] LPA is produced in the body by various enzymes and is known to transmit signals into cells by binding to G protein-coupled receptors on the cell surface, thereby exhibiting various physiological effects. Six subtypes of LPA receptors are known, from LPA1 to LPA6. The three receptors LPA1 (LPAR1), LPA2 (LPAR2), and LPA3 (LPAR3) belong to the EDG (Endotherial Differentiation Gene) family and are called EDG2, EDG4, and EDG7, respectively. LPA4 to LPA6 receptors belong to the non-EDG family and have low homology to the aforementioned EDG family. LPA receptor subtypes are distributed throughout the body, but their localization differs depending on the subtype, and it is thought that each subtype contributes to the physiological function of different tissues.

[0004] LPA has been shown to be involved in various fibrotic diseases, and the involvement of the EDG receptor family in particular has been suggested. Regarding pulmonary fibrosis, elevated LPA concentrations have been reported in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and in bleomycin-induced pulmonary fibrosis model mice, and in the same model mice, the progression of fibrosis has been significantly suppressed in Lpar1-deficient mice and mice administered with LPA1 receptor antagonists (see Non-Patent Literature 1). Similarly, serum LPA concentrations are elevated in patients with systemic sclerosis, and LPA1 receptor antagonists and LPA1 / 3 receptor antagonists have been reported to show fibrosis-inhibiting effects in bleomycin-induced cutaneous fibrosis model mice (see Non-Patent Literature 2-4). In renal fibrosis, LPA production is enhanced in unilateral ureteral ligation model mice, and fibrosis formation has been suppressed in Lpar1-deficient mice and with LPA1 receptor antagonists (see Non-Patent Literature 4, 5). Furthermore, regarding liver fibrosis, elevated blood LPA concentrations have been reported in patients with chronic hepatitis C, and the degree of this elevation has been reported to correlate with the histological stage of fibrosis (see Non-Patent Literature 6). In addition, autotaxin, an LPA-producing enzyme, is upexpressed in the blood of patients with non-alcoholic fatty liver disease (NAFLD), and autotaxin inhibitors have been shown to have an inhibitory effect in various mouse liver injury models (see Non-Patent Literature 7 and 8). Moreover, high concentrations of LPA accumulate in atherosclerotic plaques, resulting in increased inflammation and apoptosis induction, but it has been reported that lesions in model mice improve with the administration of LPA1 / 3 receptor antagonists, suggesting the involvement of LPA in cardiovascular disease (see Non-Patent Literature 9). Furthermore, LPA is known to induce the migration and proliferation of cancer cells, and elevated LPA concentrations and LPA1 receptor expression have been observed in the tissues of various cancer patients (see Non-Patent Documents 10-12). In addition, LPA has been reported to contract bladder smooth muscle cells, promote the proliferation of prostate cells, and be involved in urethral pressure control in vivo, suggesting its involvement in lower urinary tract diseases (see Patent Document 1, Non-Patent Documents 13, 14). Furthermore, LPA and LPA receptors are expressed in the nervous system, and it has been shown that LPA induces neuropathic pain through the LPA1 receptor. Lpar1 knockout mice have been reported to not show pain symptoms in a mouse nerve ligation pain model (see Non-Patent Literature 15).

[0005] Substances that antagonize the LPA1 receptor have been reported, such as ring-containing alkanoic acid compounds (Patent Documents 2-4), cyclohexylcarboxylic acid compounds containing a triazole ring (Patent Document 5), and carboxylic acid compounds containing an amide structure (Patent Documents 6-7), but the urea compound of the present invention has not been disclosed. [Prior art documents] [Patent Documents]

[0006] [Patent Document 1] WO02 / 062389 [Patent Document 2] WO03 / 099765 [Patent Document 3] WO2004 / 031118 [Patent Document 4] WO2005 / 058790 [Patent Document 5] WO2017 / 223016 [Patent Document 6] WO2015 / 025164 [Patent Document 7] WO2017 / 177004 [Non-patent literature]

[0007] [Non-Patent Document 1] Nat Med. 2008 Jan;14(1):45-54. [Non-Patent Document 2] Int J Med Sci. 2009 Jun 5;6(4):168-76. [Non-Patent Document 3] Exp Dermatol. 2015 Sep;24(9):698-702.

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Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Non-Patent Document 10

Non-Patent Document 11

Non-Patent Document 12

Non-Patent Document 13

Non-Patent Document 14

Non-Patent Document 15

Summary of the Invention

Problems to be Solved by the Invention

[0008] The object of the present invention is to provide a pharmaceutical product containing a novel compound that antagonizes the LPA1 receptor as an active ingredient. [Means for solving the problem]

[0009] As a result of diligent research to achieve the above objectives, the present inventors have discovered that a compound represented by the following formula [I] (hereinafter sometimes referred to as compound [I]) has an antagonistic effect on the LPA1 receptor.

[0010] The present invention will be described in detail below.

[0011] In other words, embodiments of the present invention are as follows.

[0012] (1) One aspect of the present invention is: The following formula [I]

[0013] [ka] {In the above formula [I], X is carboxy, C 1-4 A group selected from the following formula group [II]: alkoxycarbonyl, carbamoyl, tetrazolyl, or

[0014] [ka] Show; W is a linear C 1-3 Alkanediyl or a structure selected from the following group of formulas [III]

[0015] [ka] Show, Here, The linear C 1-3 Alkandiyl is C 1-6 Alkyl (the C 1-6The alkyl may be substituted with one group selected from the group consisting of hydroxy and carboxy. ), halo C 1-6 alkyl, C 3-8 cycloalkyl, phenyl C 1-3 alkyl, and pyridyl C 1-3 alkyl, and may be substituted with one group selected from the group consisting of and the linear C 1-3 alkanediyl is substituted with one methyl, and may be further substituted with one methyl, Ring A 1 , Ring A 2 and Ring A 3 are C 3-8 cycloalkane, a partially saturated 9- to 10-member fused-ring hydrocarbon aromatic ring, a 4- to 8-member saturated heterocyclic ring containing an oxygen atom, a 4- to 8-member saturated heterocyclic ring containing a sulfur atom, or a 4- to 8-member saturated heterocyclic ring containing a nitrogen atom, where the sulfur atom in the 4- to 8-member saturated heterocyclic ring containing the sulfur atom may be substituted with 1 to 2 oxo, the nitrogen atom in the 4- to 8-member saturated heterocyclic ring containing the nitrogen atom may be substituted with one group selected from the group consisting of C 1-4 alkylcarbonyl and C 1-4 alkoxycarbonyl, also R A11 , R A21 and R A31 are independently a hydrogen atom, hydroxy, carboxy, a halogen atom, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylcarbonyl, or a 4- to 6-member saturated heterocyclyl containing a nitrogen atom (the 4- to 6-member saturated heterocyclyl containing the nitrogen atom may be substituted with one C 1-3 alkyl. ), R A12 , R A22 and R A32 are independently a hydrogen atom, a halogen atom, or methyl, also RA11 and R A12 , R A21 and R A22 , and R A31 and R A32 These may each combine to form an oxo, moreover, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 Each of these atoms combines with the carbon atoms in the adjacent ring to form C 3-6 They may form cycloalkanes; R 1 This represents a hydrogen atom or a methyl atom; R 2 C 6-10 Alkyl, C 6-10 Alkenil, C 6-10 Alkynyl, or a group represented by the following formula [IV-1] or [IV-2]

[0016] [ka] Show, Here, Ring B 1 C 3-8 This represents a cycloalkyl, a 4-8 member saturated heterocyclyl containing a nitrogen atom, a phenyl, or a 5-6 member heteroaryl containing a nitrogen atom. R B11 and R B12 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It shows alkoxy, L 1 C 3-8 Alkanedil (the C 3-8 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) The structure represented by formula [V-6]:-CH2CH2CH=C(CH3)- or the structure represented by the following formula [V-1]

[0017] [ka] Show, Here, n11 represents an integer between 0 and 3. n12 represents an integer from 0 to 5. n13 represents an integer between 0 and 3. Also, C 3-8 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L11 )- can be replaced with, moreover, C 3-8 R is one of the two consecutive carbon atoms in an alkanediyl. 2 The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined by the formula -C(=O)N(R L12 )- can be replaced with, R L11 is a hydrogen atom or C 1-3 It indicates alkyl, R L12 is a hydrogen atom or C 1-3 It indicates alkyl, Ring B 2 This represents a partially saturated 9-10 membered fused aryl ring, or a 9-10 membered fused heteroaryl ring containing a nitrogen atom. R B21 and R B22 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It shows alkoxy, L 2 C 1-2 Alkanedil (the C 1-2 Alkanediyl may be substituted with 1 to 4 fluorine atoms. 3-6 Alkanedil (the C 3-6 The alkanediyl may be substituted with 1 to 5 fluorine atoms, or the structure represented by the following formula [V-2]

[0018] [ka] Show, Here, n21 represents an integer between 0 and 3. n22 represents an integer from 0 to 5. n23 represents an integer between 0 and 3. Also, C 3-6 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L21 )- can be replaced with, moreover, C 3-6 R is one of the two consecutive carbon atoms in an alkanediyl. 2 The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined by the formula -C(=O)N(R L22 )- can be replaced with, R L21 is a hydrogen atom or C 1-3 It indicates alkyl, R L22 is a hydrogen atom or C 1-3 It indicates alkyl; R 3 is a hydrogen atom or C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. R 4 The base is represented by the following formula [VI]

[0019] [ka] Show, Here, Ring C represents a phenyl, a 6-membered heteroaryl containing a nitrogen atom, or a 9-10 membered fused ring heteroaryl. The phenyl contains a halogen atom, C1-6 alkyl, C 1-6 alkoxy, and C 1-6 substituted with one group selected from the group consisting of alkylcarbonyl, and further, hydroxy, carboxy, carbamoyl, cyano, halogen atom, C 1-6 alkyl (the C 1-6 alkyl may be substituted with one group selected from the group consisting of hydroxy and C 1-6 alkoxy. ), haloC 1-6 alkyl (the haloC 1-6 alkyl may be substituted with one hydroxy. ), C 2-6 alkenyl, C 2-6 alkynyl, C 3-8 cycloalkyl (the C 3-8 cycloalkyl may be substituted with one hydroxy. ), C 1-6 alkoxy, haloC 1-6 alkoxy, C 3-8 cycloalkoxy, C 1-6 alkylsulfanyl, C 1-6 alkylsulfinyl, C 1-6 alkylsulfonyl, monoC 1-6 alkylamino, diC 1-6 alkylamino, C 1-6 alkylcarbonyl, haloC 1-6 alkylcarbonyl, C 1-6 alkoxycarbonyl, monoC 1-6 alkylaminocarbonyl, and diC 1-6 alkylaminocarbonyl may be substituted with 1 to 4 groups selected identically or differently from the group consisting of: the 6-membered heteroaryl containing the nitrogen atom is substituted with one C 1-6 alkoxy, and further, cyano, C 1-6 alkyl, C 1-6 alkoxy, and oxo may be substituted with 1 to 2 groups selected identically or differently from the group consisting of: the 9- to 10-membered fused-ring heteroaryl is C 1-6 alkyl, C 1-6They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkoxys and oxos; Also, R 3 and R 4 These may combine with adjacent carbon atoms to form a partially saturated 9-10 membered fused hydrocarbon aromatic ring or a partially saturated 9-10 membered fused heteroaromatic ring containing an oxygen atom. Here, The partially saturated 9-10 membered fused hydrocarbon aromatic ring may be substituted with 1-2 halogen atoms. The 9-10 membered heteroaromatic ring containing the partially saturated oxygen atom may be substituted with 1-2 halogen atoms. A pharmaceutical product containing a compound represented by or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0020] (2) Other embodiments of the present invention include: In the group of equations relating W [III], R A11 , R A21 , and R A31 These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C 1-6 Alkyl, C 1-6 Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl. R A12 , R A22 , and R A32 These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 These may each combine to form an oxo, moreover, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 Each of these atoms combines with the carbon atoms in the adjacent ring to form C 3-6 They may form cycloalkanes, R 2 In equation [IV-1] relating to, L 1 C 3-8 Alkanedil (the C 3-8 The alkanediyl may be substituted with 1 to 5 fluorine atoms, or it may represent a structure represented by formula [V-1], Here, C 3-8 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L11 )- can be replaced with, moreover, C 3-8 R is one of the two consecutive carbon atoms in an alkanediyl. 2 The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined by the formula -C(=O)N(R L12 )- can be replaced with, R L11 is a hydrogen atom or C 1-3 It indicates alkyl, R L12 is a hydrogen atom or C 1-3 A pharmaceutical product containing the compound described in (1) or a pharmaceutically acceptable salt thereof, or a hydrate thereof, which exhibits alkylity, as an active ingredient. The objective is to provide.

[0021] (3) Other aspects of the present invention include: In the above formula [I], W is a linear C 1-3 Alkanediyl or a structure selected from the following group of formulas [III]

[0022] [ka] And, Here, The linear C 1-3 Alkandiyl is C 1-6 Alkyl (the C 1-6 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl. 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl C 1-3 Alkyl and pyridyl C 1-3 It may be substituted with one group selected from the group consisting of alkyl groups. And the linear C 1-3 If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A 1 C 3-8 Cycloalkane, dihydroindene, oxetane, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, azetidine, pyrrolidine, or piperidine. Ring A 2 C 3-8 It is a cycloalkane or tetrahydropyran, Ring A 3 C 3-8 These are cycloalkanes, dihydroindenes, or tetrahydropyrans. Here, The sulfur atom in the tetrahydrothiopyran may be substituted with 1 to 2 oxo atoms. Also, Each nitrogen atom in azetidine, pyrrolidine, and piperidine is one C 1-4 It may be substituted with an alkylcarbonyl, and, R A11 These are hydrogen atoms, hydroxyl, carboxyl, halogen atoms, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6Alkyl carbonyl, or a saturated heterocycline with 4 to 6 members containing a nitrogen atom (the saturated heterocycline with 4 to 6 members containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl. R A12 This represents a hydrogen atom, a halogen atom, or a methyl atom. Also, R A11 and R A12 These may each combine to form an oxo, R A21 and R A22 Both are hydrogen atoms, R A31 and R A32 Both are hydrogen atoms, Furthermore, R A11 and R A12 Each of these atoms combines with the carbon atoms in the adjacent ring to form C 3-6 They may form cycloalkanes; R 2 However, C 6-10 Alkyl groups, or groups represented by the following formulas [IV-1] or [IV-2]

[0023] [ka] And, Here, Ring B 1 C 3-8 It is a cycloalkyl, piperidinyl, phenyl, pyrazolyl, or pyridyl, R B11 and R B12 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It is an alkoxy, L 1 The structure is represented by the following equations [V-3]~[V-12], [V-14]~[V-19].

[0024] [ka] It is one of the following: Here, n4 represents an integer between 3 and 5. n12' represents an integer between 0 and 3. n12" represents an integer from 0 to 3. Also, Ring B 2 These are dihydroindenyl, indolyl, or isoindlinyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0025] [ka] And, Here, n5 represents an integer between 1 and 2; R 4 However, the base represented by the following formula [VI]

[0026] [ka] And, Here, Ring C is phenyl, pyridyl, pyrimidinyl, dihydropyridinyl, dihydrobenzofuranyl, benzodioxanyl, indolyl, indazolyl, benzimidazolyl, pyrazolopyridinyl, indolinyl, or dihydroquinazolinyl. The phenyl contains a halogen atom, C 1-6 Alkyl, C 1-6 Alkoxy, and C 1-6 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C 1-6 Alkyl (the C 1-6 Alkyl is hydroxy and C 1-6It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C 1-6 alkyl (the halo C 1-6 The alkyl group may be substituted with one hydroxyl group. 2-6 Alkenil, C 3-8 Cycloalkyl (the C 3-8 The cycloalkyl group may be substituted with one hydroxyl group. 1-6 Alkoxy, Halo C 1-6 Alkoxy, C 3-8 Cycloalkoxy, C 1-6 Alkyl sulfinyl, C 1-6 Alkyl sulfonyl, mono C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylcarbonyl, Halo C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl and mono-C 1-6 They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkylaminocarbonyl groups. The pyridyl contains one C 1-6 Substituted with alkoxy, and further, Cyano and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. The pyrimidinyl contains one C 1-6 Substituted with alkoxy, and further, 1 C 1-6 It may be substituted with alkoxy, The dihydropyridinyl contains one C 1-6 Substituted with alkoxy, and further, C 1-6 They may be substituted with one or two groups selected identically or differently from the group consisting of alkyl and oxo. The dihydrobenzofuranyl and benzodioxanyl may be substituted with one C1-6 alkoxy. The indolyl, indazolyl, benzimidazolyl, pyrazolopyridinyl, and indolynyl are C 1-6 Alkyl and C 1-6They may be substituted with one or two groups selected identically or differently from the group consisting of alkoxys. The dihydroquinazolinyl is C 1-6 Alkyl, C 1-6 They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkoxys and oxos; Also, R 3 and R 4 However, the fused rings formed when they combine with adjacent carbon atoms are dihydroindene or dihydrobenzofuran. The dihydroindene and dihydrobenzofuran may be substituted with one or two halogens. A pharmaceutical product containing the compound described in (1) or (2) or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0027] (4) Other aspects of the present invention include: In the above formula [I], X is carboxy, C 1-4 It is an alkoxycarbonyl or tetrazolyl; R 1 However, it is a hydrogen atom; R 2 However, the base represented by the aforementioned formula [IV-1] or [IV-2]

[0028] [ka] A pharmaceutical product containing the compound described in (1) or (2) or a pharmaceutically acceptable salt thereof or a hydrate thereof as an active ingredient. The objective is to provide.

[0029] (5) Other aspects of the present invention include: In the above formula [I], W is methanediyl or a structure represented by the following formula [III-1]

[0030] [ka] And, Here, The methanediyl is C 1-6 Alkyl (the C 1-6 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl. 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl C 1-3 Alkyl and pyridyl C 1-3 It may be substituted with one group selected from the group consisting of alkyl groups. Furthermore, if the methanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Also, In the structure represented by formula [III-1], Ring A 1 C 3-8 A cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, or a 4-8 membered saturated heterocycle containing a nitrogen atom, Here, The sulfur atom in the 4-8 member saturated heterocycle containing the sulfur atom may be substituted with 1-2 oxos. Also, The nitrogen atom in the saturated heterocycle of 4 to 8 members containing the nitrogen atom is C 1-4 Alkylcarbonyl and C 1-4 It may be substituted with one group selected from the group consisting of alkoxycarbonyls. and, R A11 These are hydrogen atoms, hydroxyl, carboxyl, halogen atoms, and C 1-6 Alkyl, C 1-6 Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl. R A12 is a hydrogen atom, a halogen atom, or a methyl atom, Also, R A11 and R A12 These may each combine to form an oxo, moreover, R A11 and R A12 Each of these atoms combines with the carbon atoms in the adjacent ring to form C 3-6 They may form cycloalkanes. A pharmaceutical product containing the compound described in (1), (2), or (4) or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0031] (6) Other aspects of the present invention include: In the above formula [I], R 4 However, the base represented by the following formula [VI]

[0032] [ka] And, Here, The carbon ring is phenyl, The phenyl contains a halogen atom, C 1-6 Alkyl, C 1-6 Alkoxy, and C 1-6 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C 1-6 Alkyl (the C 1-6 Alkyl is hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C 1-6 alkyl (the halo C 1-6 The alkyl group may be substituted with one hydroxyl group. 2-6 Alkenil, C 2-6 Alkinyl, C 3-8 Cycloalkyl (the C 3-8 The cycloalkyl group may be substituted with one hydroxyl group.1-6 Alkoxy, Halo C 1-6 Alkoxy, C 3-8 Cycloalkoxy, C 1-6 Alkyl sulfanyl, C 1-6 Alkyl sulfinyl, C 1-6 Alkyl sulfonyl, mono C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylcarbonyl, Halo C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, monoC 1-6 Alkylaminocarbonyl and diC 1-6 They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkylaminocarbonyl groups. A pharmaceutical product containing any one of the compounds described in (1), (2), (4), or (5), or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0033] (7) Other aspects of the present invention include: In the above formula [I], R 2 However, the base represented by the following formula [IV-1] or [IV-2]

[0034] [ka] And, Here, Ring B 1 It is phenyl, R B11 and R B12 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It is an alkoxy, L 1 However, the structure can be represented by the following equations [V-3]~[V-5], [V-7]~[V-8], [V-11]~[V-12], [V-14]~[V-16].

[0035] [ka] It is one of the following: Here, n4 represents an integer between 3 and 5. Ring B 2 These are dihydroindenyl, indolyl, or isoindlinyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0036] [ka] And, Here, n5 is an integer between 1 and 2. A pharmaceutical product containing any one of the compounds described in (1), (2), (4) to (6), or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0037] (8) Other aspects of the present invention include: In the above formula [I], X is a carboxyl; W is a structure represented by the following equations [III-4] to [III-17].

[0038] [ka] It is either one of the following; R 2 However, the base represented by the following formula [IV-1] or [IV-2]

[0039] [ka] And, Here, Ring B 1 It is phenyl, R B11 and R B12 The same is true for hydrogen atoms And, L 1 However, the structure is represented by the following formulas [V-3], [V-8], [V-12], [V-14], or [V-15].

[0040] [ka] And, Here, n4 is an integer between 3 and 4. Also, Ring B 2 It is dihydroindenyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0041] [ka] And, Here, n5 is 2; R 3 However, the spatial configuration is represented by the following equation [VII]

[0042] [ka] It is a methyl compound having; R 4 However, the base is represented by any of the following formulas [VI-1] to [VI-21]

[0043] [ka]

[0044] [ka]

[0045] [ka] A pharmaceutical product containing any one of the compounds described in (4) to (7), or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0046] (9) Other aspects of the present invention include: In the above formula [I], X is a carboxyl; W is a structure represented by the following formulas [III-4]~[III-11], [III-13]~[III-14], or [III-18]~[III-19].

[0047] [ka] and; R 2 However, the base represented by the following formula [IV-1] or [IV-2]

[0048] [ka] And, Here, Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 However, the structure is represented by the following formulas [V-3], [V-8], or [V-14].

[0049] [ka] And, Here, n4 is 4, Also, Ring B 2 It is dihydroindenyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0050] [ka] And, Here, n5 is 2; R 3 However, the spatial configuration is represented by the following equation [VII]

[0051] [ka] It is a methyl compound having; R 4 However, the base represented by the following formulas [VI-2], [VI-3], [VI-8], [VI-10] to [VI-12], [VI-16], [VI-19], or [VI-21]

[0052] [ka]

[0053] [ka] A pharmaceutical product containing any one of the compounds described in (4) to (7), or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0054] (10) Other aspects of the present invention include: In the above formula [I], X is a carboxyl or tetrazolyl; W is a structure represented by the following formulas [III-5], [III-8] to [III-11], or [III-13].

[0055] [ka] and; R 2 However, the base represented by the following formula [IV-1] or [IV-2]

[0056] [ka] And, Here, Ring B 1 It is phenyl, R B11 and R B12 The same is true for hydrogen atoms And, L 1 However, the structure is represented by the following formulas [V-3], [V-12], or [V-14].

[0057] [ka] And, Here, n4 is an integer of 4, Also, Ring B 2 It is dihydroindenyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0058] [ka] And, Here, n5 is 2; R 3 However, the spatial configuration is represented by the following equation [VII]

[0059] [ka] It is a methyl compound having; R 4 However, the base is represented by the following formulas [VI-2], [VI-7], [VI-8], [VI-10], [VI-11], or [VI-12].

[0060] [ka] A pharmaceutical product containing any one of the compounds described in (4) to (7), or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide.

[0061] (11) Other aspects of the present invention include: A pharmaceutical product containing any of the following compounds or pharmaceutically acceptable salts thereof, or hydrates thereof, as an active ingredient, as described in (1) The purpose is to provide:

[0062] [ka]

[0063] [ka]

[0064] [ka]

[0065] [ka]

[0066] [ka]

[0067] (12) Other aspects of the present invention include: A pharmaceutical product containing any of the following compounds or pharmaceutically acceptable salts thereof, or hydrates thereof, as an active ingredient, as described in (1) The purpose is to provide:

[0068] [ka]

[0069] [ka]

[0070] [ka]

[0071] (13) Other aspects of the present invention include: The objective is to provide a pharmaceutical product containing any one of the compounds described in (1) to (12), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient. (14) Other aspects of the present invention include: A pharmaceutical product containing any one of the compounds described in (1) to (12), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient, Furthermore, it contains pharmaceutically acceptable additives and is a pharmaceutical solid composition for oral use. The objective is to provide.

[0072] (15) Other aspects of the present invention include: The pharmaceutical product described in (14) is characterized by having one or more pharmaceutically acceptable additives selected from the group consisting of water, lactose, dextrose, fructose, sucrose, sorbitol, mannitol, polyethylene glycol, propylene glycol, starch, corn starch, gum, gelatin, alginate, calcium silicate, calcium phosphate, cellulose, water syrup, methylcellulose, polyvinylpyrrolidone, alkyl parahydroxybenzoate, talc, stearic acid, magnesium stearate, agar, pectin, acacia gum, glycerin, sesame oil, olive oil, soybean oil, cocoa butter, ethylene glycol, low viscosity hydroxypropylcellulose (HPC-L), microcrystalline cellulose, carboxymethylcellulose (CMC), and sodium carboxymethylcellulose (CMC-Na). The objective is to provide.

[0073] (16) Other aspects of the present invention include: The pharmaceutical product described in (14) or (15), wherein the pharmaceutical product is in the form of a tablet, pill, capsule, granule, powder, or powder. The objective is to provide.

[0074] (17) Other aspects of the present invention include: A pharmaceutical product as described in any of (14) to (16), wherein the dosage of the compound or a pharmaceutically acceptable salt thereof or a hydrate thereof is 0.1 mg to 1000 mg / day. The objective is to provide. (18) Other aspects of the present invention include: The objective is to provide an LPA1 receptor antagonist containing any one of the compounds described in (1) to (17), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient. (19) Other aspects of the present invention include: The objective is to provide a preventive or therapeutic agent for systemic sclerosis containing any one of the compounds described in (1) to (17), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

[0075] (20) Other embodiments of the present invention include: The following formula [Ia]

[0076] [ka] {In the above formula [Ia], X is carboxy, C 1-4 A structure selected from the following group of formulas [IIa]: alkoxycarbonyl, carbamoyl, tetrazolyl, or

[0077] [ka] Show; W is a linear C 1-3 Alkanediyl or a structure selected from the following group of formulas [IIIa]

[0078] [ka] Show, Here, The linear C 1-3 Alkandiyl is C 1-6 Alkyl (the C 1-6 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl. 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl C 1-3 Alkyl and pyridyl C 1-3 It may be substituted with one group selected from the group consisting of alkyl groups. And the linear C 1-3 If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A 1 , ring A 2 , and ring A 3 C 3-8This refers to a cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a partially saturated 9-10 membered fused saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, a partially saturated 9-10 membered fused saturated heterocycle containing a nitrogen atom, a 4-8 membered saturated heterocycle containing a nitrogen atom, or a partially saturated 9-10 membered fused saturated heterocycle containing a sulfur atom. Here, Each sulfur atom in the saturated heterocycle of a 4-8 member containing the sulfur atom and the saturated heterocycle of a 9-10 member fused ring containing the partially saturated sulfur atom may be substituted with 1-2 oxos. Also, Each nitrogen atom in the saturated heterocycle of a 4-8 member containing the nitrogen atom and the saturated heterocycle of a 9-10 member fused ring containing the partially saturated nitrogen atom is C 1-4 Alkylcarbonyl and C 1-4 It may be substituted with one group selected from the group consisting of alkoxycarbonyls. R A11 , R A21 , and R A31 These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Alkyl carbonyl, or a saturated heterocycline with 4 to 6 members containing a nitrogen atom (the saturated heterocycline with 4 to 6 members containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl. R A12 , R A22 , and R A32 These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 These may each combine to form an oxo, Furthermore, R A11 and R A12 , RA21 and R A22 , and R A31 and R A32 Each of these atoms combines with the carbon atoms in the adjacent ring A to form C 3-6 They may form cycloalkanes; R 1 This represents a hydrogen atom or a methyl atom; R 2 C 1-10 Alkyl, C 2-10 Alkenil, C 2-10 Alkynyl, or the group represented by the following formula [IVa]

[0079] [ka] Show, Here, Ring B is C 3-8 This refers to cycloalkyl, 4-8 member saturated heterocyclyl, phenyl, 9-10 member fused ring aryl, 5-6 member heteroaryl, or 9-10 member fused ring heteroaryl. R B1 and R B2 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, C 1-6 It shows alkoxy, L is C 1-2 Alkanedil (the C 1-2 Alkanediyl may be substituted with 1 to 4 fluorine atoms. 3-8 Alkanedil (the C 3-8 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) The structure represented by formula [V-6]:-CH2CH2CH=C(CH3)- or the structure represented by the following formula [V-1a]

[0080] [ka] Show, Here, n1 represents an integer between 0 and 3. n2 represents an integer between 0 and 5. n3 represents an integer between 0 and 3. Also, C 3-8 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L1 )- can be replaced with, moreover, C 3-8 R is one of the two consecutive carbon atoms in an alkanediyl. 2 The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined by the formula -C(=O)N(R L2 )- can be replaced with, R L1 is a hydrogen atom or C 1-3 It indicates alkyl, R L2 is a hydrogen atom or C 1-3 It indicates alkyl; R 3 is a hydrogen atom or C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. R 4 The base is represented by the following formula [VIa]

[0081] [ka] Show, Here, Ring C represents a phenyl group, a 9-10 member fused aryl group, a 5-6 member heteroaryl group, or a 9-10 member fused heteroaryl group. The phenyl is a hydroxy, carboxy, carbamoyl, cyano, halogen atom, C 1-6 Alkyl (the C 1-6 Alkyl is hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C 1-6 alkyl (the halo C1-6 Alkyl is hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), C 2-6 Alkenil, C 2-6 Alkinyl, C 3-8 Cycloalkyl (the C 3-8 Cycloalkyls are hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), C 1-6 Alkoxy, Halo C 1-6 Alkoxy (the C 1-6 Alkoxy and Halo C 1-6 Alkoxy is composed of hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), C 3-8 Cycloalkoxy (the C 3-8 Cycloalkoxys are composed of hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), C 1-6 Alkyl sulfanyl, C 1-6 Alkyl sulfinyl, C 1-6 Alkylsulfonyl (the C 1-6 Alkyl sulfanyl, C 1-6 Alkyl sulfinyl, and C 1-6 Alkylsulfonyls are hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), monoC 1-6 Alkylamino, diC 1-6 Alkylamino (the mono C) 1-6 Alkylamino and diC 1-6 Alkylaminos are hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), C 1-6 Alkylcarbonyl, Halo C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, monoC 1-6 Alkylaminocarbonyl and diC 1-6 Alkylaminocarbonyl (the C 1-6 Alkylcarbonyl, Halo C 1-6 Alkylcarbonyl, C1-6 Alkoxycarbonyl, monoC 1-6 Alkylaminocarbonyl and diC 1-6 Alkylaminocarbonyl is a compound of hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys.) It may also be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkoxys. The aryl group of the 9-10 member fused ring is a halogen atom, C 1-6 Alkyl and C 1-6 They may be substituted with 1 to 3 groups selected identically or differently from the group consisting of alkoxys. The 5-6 member heteroaryl is composed of a halogen atom, cyano, and C 1-6 Alkyl, C 1-6 They may be substituted with 1 to 3 groups selected identically or differently from the group consisting of alkoxys and oxos. The 9-10 member fused ring heteroaryl is C 1-6 Alkyl, C 1-6 They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkoxys and oxos; Also, R 3 and R 4 These, together with the adjacent carbon atoms, A partially saturated 9-10 member fused hydrocarbon aromatic ring or a partially saturated 9-10 member fused heteroaromatic ring may be formed. Here, The partially saturated 9-10 membered fused hydrocarbon aromatic ring may be substituted with 1-2 halogen atoms. The partially saturated 9-10 member heteroaromatic ring may be substituted with 1-2 halogen atoms. LPA1 receptor antagonists containing a compound represented by or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient. The objective is to provide. (21) Other aspects of the present invention include: In the group of equations [IIIa] relating to W, R A11, R A21 , and R A31 These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C 1-6 Alkyl, C 1-6 Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl. R A12 , R A22 , and R A32 These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 These may each combine to form an oxo, moreover, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 Each of these atoms combines with the carbon atoms in the adjacent ring A to form C 3-6 They may form cycloalkanes, R 2 In equation [IVa] relating to, L is C 1-2 Alkanedil (the C 1-2 Alkanediyl may be substituted with 1 to 4 fluorine atoms. 3-8 Alkanedil (the C 3-8 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) or the structure represented by formula [V-1a] is shown, where, C 3-8 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L1 )- can be replaced with, moreover, C 3-8R is one of the two consecutive carbon atoms in an alkanediyl. 2 The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined by the formula -C(=O)N(R L2 )- can be replaced with, R L1 is a hydrogen atom or C 1-3 It indicates alkyl, R L2 is a hydrogen atom or C 1-3 LPA1 receptor antagonists exhibiting alkylity as described in (16) The objective is to provide.

[0082] (22) Other aspects of the present invention include: The objective is to provide a preventive or therapeutic agent for systemic sclerosis containing as an active ingredient a compound represented by formula [Ia] as described in (20) or (21), a pharmaceutically acceptable salt thereof, or a hydrate thereof. (23) Other aspects of the present invention include: The present invention provides a method for preventing or treating systemic sclerosis, comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound represented by formula [Ia] as described in (20) or (21), or a pharmaceutically acceptable salt thereof, or a hydrate thereof. (24) Other aspects of the present invention include: The objective is to provide a pharmaceutical product containing a compound represented by formula [Ia] as described in (20) or (21), a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient. [Effects of the Invention]

[0083] The compound of the present invention (hereinafter sometimes referred to as "the compound of the present invention") has an antagonistic effect on the LPA1 receptor. [Modes for carrying out the invention]

[0084] The present invention provides a pharmaceutical product containing as an active ingredient a compound represented by formula [I] having an antagonistic effect on the LPA1 receptor, or a pharmaceutically acceptable salt thereof, or a hydrate thereof.

[0085] The compounds of the present invention will be described in more detail below, but the present invention is not limited to those exemplified.

[0086] "Halogen atoms" refer to fluorine atoms, chlorine atoms, bromine atoms, and iodine atoms.

[0087] "C 1-3 "Alkyl" refers to a linear or branched alkyl group having 1 to 3 carbon atoms. Examples include methyl, ethyl, n-propyl, and isopropyl alkyl groups. "C 1-4 "Alkyl" refers to linear or branched alkyl groups having 1 to 4 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, and tert-butyl. "C 1-6 "Alkyl" refers to linear or branched alkyl groups having 1 to 6 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, and n-hexyl. "C 1-10 "Alkyl" refers to linear or branched alkyl groups having 1 to 10 carbon atoms. Examples include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isoheptyl, and isooctyl. "C 6-10 "Alkyl" refers to linear or branched alkyl groups having 6 to 10 carbon atoms. Examples include n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, isoheptyl, and isooctyl. "C 5-9 "Alkyl" refers to linear or branched alkyl groups having 5 to 9 carbon atoms. Examples include n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, isoheptyl, and isooctyl.

[0088] "Hello C1-6 "Alkyl" refers to a linear or branched alkyl group having 1 to 6 carbon atoms substituted with halogen atoms. The preferred number of halogen atoms is 1 to 5, and the preferred halogen atom is the fluorine atom. Examples include monofluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoroethyl, 1,1-difluoroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 1,1,2,2,2-pentafluoroethyl, 3,3,3-trifluoropropyl, 4,4,4-trifluorobutyl, 5,5,5-trifluoropentyl, and 6,6,6-trifluorohexyl. "Hydroxy C 1-6 "Alkyl" refers to a linear or branched alkyl group having 1 to 6 carbon atoms substituted with hydroxyl groups. A preferred number of hydroxyl groups is one. Examples include monohydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 3-hydroxypropyl, 4-hydroxybutyl, 5-hydroxypentyl, and 6-hydroxyhexyl.

[0089] "C 2-3 "Alkenyl" refers to a linear or branched alkenyl having 2 to 3 carbon atoms. Examples include ethenyl, (E)-propa-1-en-1-yl, (Z)-propa-1-en-1-yl, propa-1-en-2-yl, and propa-2-en-1-yl. "C 2-6 "Alkenyl" refers to a linear or branched alkenyl having 2 to 6 carbon atoms. Examples include ethenyl, (E)-propa-1-en-1-yl, (Z)-propa-1-en-1-yl, propa-2-en-1-yl, buta-3-en-1-yl, penta-4-en-1-yl, hexa-5-en-1-yl, and 1-methylethenyl. "C 2-10"Alkenyl" refers to a linear or branched alkenyl having 2 to 10 carbon atoms. Examples include ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, sec-butenyl, tert-butenyl, n-pentenyl, n-hexenyl, n-heptenyl, n-octenyl, n-nonenyl, and n-decenyl. "C 5-9 An "alkenyl" refers to a linear or branched alkenyl having 5 to 9 carbon atoms. Examples include n-pentenyl, n-hexenyl, n-heptenyl, n-octenyl, and n-nonenyl. "C 6-10 An "alkenyl" refers to a linear or branched alkenyl having 6 to 10 carbon atoms. Examples include n-hexenyl, n-heptenyl, n-octenyl, n-nonenyl, and n-decenyl.

[0090] "C 2-6 "Alkynyl" refers to linear or branched alkynyl molecules having 2 to 6 carbon atoms. Examples include ethynyl, propa-1-in-1-yl, propa-2-in-1-yl, buta-3-in-1-yl, penta-4-in-1-yl, and hexa-5-in-1-yl. "C 2-10 "Alkynyl" refers to linear or branched alkynyl molecules having 2 to 10 carbon atoms. Examples include ethynyl, n-propynyl, n-butynyl, n-pentynyl, n-hexynyl, n-heptynyl, n-octinyl, n-noninyl, and n-decinyl. "C 5-9 "Alkynyl" refers to linear or branched alkynyl molecules having 5 to 9 carbon atoms. Examples include n-pentinyl, n-hexinyl, n-heptinyl, n-octinyl, and n-noninyl. "C 6-10 "Alkynyl" refers to linear or branched alkynyl molecules having 6 to 10 carbon atoms. Examples include n-hexynyl, n-heptinyl, n-octinyl, n-noninyl, and n-decinyl.

[0091] "C 3-6A "cycloalkane" refers to a hydrocarbon ring containing 3 to 6 carbon atoms. Examples include cyclopropane, cyclobutane, cyclopentane, and cyclohexane. "C 3-8 "Cycloalkanes" refer to hydrocarbon rings containing 3 to 8 carbon atoms. Examples include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, and cyclooctane.

[0092] "C 3-8 "Cycloalkyl" refers to a cyclic alkyl group having 3 to 8 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl.

[0093] "9-10 membered fused aryl group" refers to a 9-10 membered fused polycyclic hydrocarbon aromatic ring group having 9-10 carbon atoms. Naphthyl is an example. Furthermore, in the 9-10 membered fused ring aryl, partially saturated groups are also included in "9-10 membered fused ring aryl." Examples include dihydroindenyl, dihydronaphthyl, and tetrahydronaphthyl.

[0094] A "partially saturated 9-10 member fused polycyclic hydrocarbon aromatic ring" refers to a partially saturated 9-10 member fused polycyclic hydrocarbon aromatic ring having 9-10 carbon atoms. Examples include dihydroindene, dihydronaphthalene, and tetrahydronaphthalene.

[0095] "Partially saturated 9-10 membered fused aryl groups" refer to partially saturated 9-10 membered fused polycyclic hydrocarbon aromatic ring groups having 9-10 carbon atoms. Examples include dihydroindenyl, dihydronaphthyl, and tetrahydronaphthyl.

[0096] "4-8 member saturated heterocyclyl" refers to a 4-8 member monocyclic saturated heterocyclic group consisting of one atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms and 3-7 carbon atoms. Here, in addition to the aforementioned oxygen, sulfur, or nitrogen atoms, it may also contain one more atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms. Examples include oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothiopyranyl, azetidinyl, pyrrolidinyl, piperidinyl, oxazolidinyl, thiazolidinyl, imidazolidinyl, morpholinyl, thiomorpholinyl, and piperazinyl.

[0097] A "saturated heterocycle with 4 to 8 members containing an oxygen atom" refers to a monocyclic saturated heterocycle with 4 to 8 members, consisting of one oxygen atom and 3 to 7 carbon atoms. Examples include oxetane, tetrahydrofuran, and tetrahydropyran.

[0098] A "saturated heterocycle with 4 to 8 members containing a sulfur atom" refers to a monocyclic saturated heterocycle with 4 to 8 members, consisting of one sulfur atom and 3 to 7 carbon atoms. Examples include thietan, tetrahydrothiophene, and tetrahydrothiopyran.

[0099] A "saturated heterocycle with 4 to 8 members containing a nitrogen atom" refers to a monocyclic saturated heterocycle with 4 to 8 members consisting of one nitrogen atom and 3 to 7 carbon atoms. In addition to the aforementioned nitrogen atom, it may also contain one atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms. Examples include azetidine, pyrrolidine, piperidine, azepane, morpholine, thiomorpholine, and piperazine.

[0100] "A 4-6 member saturated heterocycline containing a nitrogen atom" refers to a 4-6 member monocyclic saturated heterocyclic group consisting of one nitrogen atom and three to five carbon atoms. In addition to the aforementioned nitrogen atom, it may also contain one atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms. Examples include azetidinyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, and piperazinyl.

[0101] "A 4-8 member saturated heterocycline containing a nitrogen atom" refers to a 4-8 member monocyclic saturated heterocyclic group consisting of one nitrogen atom and 3-7 carbon atoms. In addition to the aforementioned nitrogen atom, it may also contain one atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms. Examples include azetidinyl, pyrrolidinyl, piperidinyl, azepanil, morpholinyl, thiomorpholinyl, and piperazinyl.

[0102] A "5-6 membered heteroaryl" refers to a 5-6 membered monocyclic aromatic heterocyclic group consisting of one or more atoms identically or differently selected from the group consisting of oxygen, sulfur, and nitrogen atoms, and 1 to 5 carbon atoms. Examples include furanyl, thiophenyl, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl. Furthermore, in the case of the 5-6 membered heteroaryl, partially saturated groups are also included in the "5-6 membered heteroaryl." Examples include dihydrothiazolyl, dihydropyridinyl, and tetrahydropyridinyl.

[0103] "A 5-6 membered heteroaryl group containing a nitrogen atom" refers to a 5-6 membered monocyclic aromatic heterocyclic group consisting of 1-4 nitrogen atoms and 1-5 carbon atoms, wherein, in addition to the nitrogen atoms, it may also contain one atom selected from the group consisting of oxygen atoms and sulfur atoms. Examples include pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl. Furthermore, in a 5-6 membered heteroaryl containing a nitrogen atom, partially saturated groups are also included in "5-6 membered heteroaryls containing a nitrogen atom." Examples include dihydrothiazolyl, dihydropyridinyl, and tetrahydropyridinyl.

[0104] A "six-membered heteroaryl group containing a nitrogen atom" refers to a six-membered monocyclic aromatic heterocyclic group consisting of one to three nitrogen atoms and three to five carbon atoms. Examples include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl. Furthermore, in a six-membered heteroaryl containing a nitrogen atom, partially saturated groups are also included in the definition of "six-membered heteroaryl containing a nitrogen atom." Examples include dihydropyridinyl and tetrahydropyridinyl.

[0105] "9-10 member fused ring heteroaryl" refers to a 9-10 member fused polycyclic aromatic heterocyclic group consisting of one atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms and 5-9 carbon atoms. Herein, in addition to the aforementioned oxygen, sulfur, or nitrogen atoms, it may also contain 1-3 atoms selected identically or differently from the group consisting of oxygen, sulfur, and nitrogen atoms. Examples include benzofuranyl, benzothiophenyl, indolyl, indazolyl, benzimidazolyl, and pyrazolopyridinyl. Furthermore, in the 9-10 member fused ring heteroaryl, partially saturated groups are also included in the "9-10 member fused ring heteroaryl." Examples include dihydrobenzofuranyl, dihydrobenzothiophenyl, indolinyl, dihydrobenzodioxynyl, dihydroquinazolinyl, and isoindolinyl.

[0106] A "partially saturated 9-10 member fused heteroaromatic ring" refers to a partially saturated 9-10 member fused polycyclic aromatic heterocycle consisting of one atom selected from the group consisting of oxygen, sulfur, and nitrogen atoms, and 5-9 carbon atoms, wherein, in addition to the aforementioned oxygen, sulfur, or nitrogen atoms, it may also contain 1-3 additional atoms selected identically or differently from the group consisting of oxygen, sulfur, and nitrogen atoms. Examples include dihydrobenzofuran, dihydrobenzothiophene, indoline, dihydrobenzodioxin, and dihydroquinazoline.

[0107] "A 9-10 membered fused heteroaryl group containing a nitrogen atom" refers to a 9-10 membered fused polycyclic aromatic heterocyclic group consisting of one nitrogen atom and 5-9 carbon atoms, wherein, in addition to the nitrogen atom, it may also contain 1-3 atoms selected identically or differently from the group consisting of oxygen atoms, sulfur atoms, and nitrogen atoms. Examples include indolyl, indazolyl, benzimidazolyl, and pyrazolopyridinyl. Furthermore, in a 9-10 membered fused ring heteroaryl containing a nitrogen atom, partially saturated groups are also included in "9-10 membered fused ring heteroaryl containing a nitrogen atom." Examples include indolinyl and dihydroquinazolinyl.

[0108] "A 9-10 membered fused heterocycle containing a partially saturated oxygen atom" refers to a partially saturated 9-10 membered fused polycyclic aromatic heterocycle consisting of one oxygen atom and 5-9 carbon atoms, wherein, in addition to the oxygen atom, it may also contain 1-3 atoms identically or differently selected from the group consisting of oxygen, sulfur, and nitrogen atoms. For example, dihydrobenzofuran is an example.

[0109] "A 9-10 membered fused heterocycle containing a partially saturated sulfur atom" refers to a partially saturated 9-10 membered fused polycyclic aromatic heterocycle consisting of one sulfur atom and 5-9 carbon atoms, wherein, in addition to the sulfur atom, it may also contain 1-3 atoms selected identically or differently from the group consisting of oxygen, sulfur, and nitrogen atoms. An example is dihydrobenzothiophene.

[0110] "A 9-10 membered fused heterocycle containing a partially saturated nitrogen atom" refers to a partially saturated 9-10 membered fused polycyclic aromatic heterocycle consisting of one nitrogen atom and 5-9 carbon atoms, wherein, in addition to the nitrogen atom, it may also contain 1-3 atoms selected identically or differently from the group consisting of oxygen atoms, sulfur atoms, and nitrogen atoms. An example is indoline.

[0111] "Phenyl C 1-3"Alkyl" refers to the aforementioned "C" which has one phenyl substituent. 1-3 This indicates "alkyl." Examples include benzyl, phenethyl, and 3-phenylpropyl. "Pyridyl C 1-3 "Alkyl" refers to the aforementioned "C" which has one pyridyl substituent. 1-3 This indicates "alkyl". Examples include (pyridine-2-yl)methyl, (pyridine-3-yl)methyl, (pyridine-4-yl)methyl, 2-(pyridine-2-yl)ethyl, and 3-(pyridine-2-yl)propyl.

[0112] "C 1-4 "Alkoxy" refers to linear or branched alkoxy molecules having 1 to 4 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, and tert-butoxy. "C 1-6 "Alkoxy" refers to linear or branched alkoxy molecules having 1 to 6 carbon atoms. Examples include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentyloxy, and n-hexyloxy.

[0113] "Hello C 1-6 "Alkoxy" refers to a linear or branched alkoxy having 1 to 6 carbon atoms substituted with halogen atoms. The preferred number of halogen atoms is 1 to 5, and the preferred halogen atom is the fluorine atom. Examples include monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 1-fluoroethoxy, 1,1-difluoroethoxy, 2-fluoroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2,2-pentafluoroethoxy, 3,3,3-trifluoropropoxy, 4,4,4-trifluorobutoxy, 5,5,5-trifluoropentyloxy, and 6,6,6-trifluorohexyloxy.

[0114] "C 3-8A "cycloalkoxy" refers to a cyclic alkoxy having 3 to 8 carbon atoms. Examples include cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, and cyclooctyloxy.

[0115] "C 1-6 "Alkyl sulfanyl" refers to the aforementioned "C 1-6 This refers to a group in which an alkyl group is bonded to a sulfanil group. Examples include methylsulfanil, ethylsulfanil, n-propylsulfanil, isopropylsulfanil, n-butylsulfanil, isobutylsulfanil, sec-butylsulfanil, tert-butylsulfanil, n-pentylsulfanil, and n-hexylsulfanil.

[0116] "C 1-6 "Alkyl sulfinyl" refers to the aforementioned "C 1-6 This refers to a group in which an alkyl group is bonded to a sulfinyl group. Examples include methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl, tert-butylsulfinyl, n-pentylsulfinyl, and n-hexylsulfinyl.

[0117] "C 1-6 "Alkyl sulfonyl" refers to the aforementioned "C 1-6 This refers to a group formed by the bonding of an alkyl group and a sulfonyl group. Examples include methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, n-pentylsulfonyl, and n-hexylsulfonyl. "C 1-4 "Alkyl sulfonyl oxy" refers to the aforementioned "C 1-4This refers to a group formed by the bonding of an alkyl group with a sulfonyloxy group. Examples include methylsulfonyloxy, ethylsulfonyloxy, n-propylsulfonyloxy, isopropylsulfonyloxy, n-butylsulfonyloxy, isobutylsulfonyloxy, sec-butylsulfonyloxy, and tert-butylsulfonyloxy.

[0118] "MonoC 1-6 "Alkylamino" refers to the aforementioned "C 1-6 This refers to an amino acid having one alkyl group as a substituent. Examples include methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, n-pentylamino, and n-hexylamino.

[0119] "JiC 1-6 "Alkylamino" refers to the aforementioned "C 1-6 This term refers to an amino acid having two identical or different alkyl substituents. Examples include dimethylamino, diethylamino, di(n-propyl)amino, di(isopropyl)amino, ethylmethylamino, and methyl(n-propyl)amino.

[0120] "C 1-4 "Alkyl carbonyl" refers to the aforementioned "C 1-4 This refers to a group formed by the bonding of an alkyl group with a carbonyl group. Examples include methyl carbonyl, ethyl carbonyl, n-propyl carbonyl, isopropyl carbonyl, n-butyl carbonyl, isobutyl carbonyl, sec-butyl carbonyl, and tert-butyl carbonyl. "C 1-6 "Alkyl carbonyl" refers to the aforementioned "C 1-6 This refers to a group formed by the bonding of an alkyl group with a carbonyl group. Examples include methyl carbonyl, ethyl carbonyl, n-propyl carbonyl, isopropyl carbonyl, n-butyl carbonyl, isobutyl carbonyl, sec-butyl carbonyl, tert-butyl carbonyl, n-pentyl carbonyl, and n-hexyl carbonyl.

[0121] "Hello C 1-6 "Alkylcarbonyl" refers to the aforementioned "halo C 1-6 This refers to a group in which an alkyl group is bonded to a carbonyl group. The preferred number of halogen atoms is 1 to 5, and the preferred halogen atom is the fluorine atom. Examples include monofluoromethyl carbonyl, difluoromethyl carbonyl, trifluoromethyl carbonyl, 1-fluoroethyl carbonyl, 1,1-difluoroethyl carbonyl, 2-fluoroethyl carbonyl, 2,2,2-trifluoroethyl carbonyl, 1,1,2,2,2-pentafluoroethyl carbonyl, 3,3,3-trifluoropropyl carbonyl, 4,4,4-trifluorobutyl carbonyl, 5,5,5-trifluoropentyl carbonyl, and 6,6,6-trifluorohexyl carbonyl.

[0122] "C 1-4 "Alkoxycarbonyl" refers to the aforementioned "C 1-4 This refers to a group formed by the bonding of an "alkoxy" and a carbonyl group. Examples include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, and tert-butoxycarbonyl. "C 1-6 "Alkoxycarbonyl" refers to the aforementioned "C 1-6 This refers to a group in which an "alkoxy" and a carbonyl group are bonded. Examples include methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, n-pentyloxycarbonyl, and n-hexyloxycarbonyl.

[0123] "MonoC 1-6 "Alkylaminocarbonyl" refers to the aforementioned "mono-C 1-6This refers to a group formed by the bonding of an alkylamino group with a carbonyl group. Examples include methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, n-butylaminocarbonyl, isobutylaminocarbonyl, sec-butylaminocarbonyl, tert-butylaminocarbonyl, n-pentylaminocarbonyl, and n-hexylaminocarbonyl.

[0124] "JiC 1-6 "Alkylaminocarbonyl" refers to the aforementioned "diC 1-6 This refers to a group formed by the bonding of an alkylamino group with a carbonyl group. Examples include dimethylaminocarbonyl, diethylaminocarbonyl, di(n-propyl)aminocarbonyl, di(isopropyl)aminocarbonyl, ethylmethylaminocarbonyl, and methyl(n-propyl)aminocarbonyl.

[0125] "Oxo" refers to a substituent (=O) that replaces an oxygen atom via a double bond. Therefore, when an oxo substitutes a carbon atom, it forms a carbonyl molecule together with that carbon atom; when one oxo substitutes a sulfur atom, it forms a sulfinyl molecule together with that sulfur atom; and when two oxo substitutes a sulfur atom, it forms a sulfonyl molecule together with that sulfur atom. Examples of saturated heterocyclyls substituted with oxo include 2-oxopyrrolidinyl, 2-oxopiperidinyl, 2-oxopiperazinyl, 1,1-dioxidetetrahydrothiophenyl, 1-oxidetetrahydro-2H-thiopyranyl, 1,1-dioxidetetrahydro-2H-thiopyranyl, 1,1-dioxideisothiazolidinyl, 2-oxo-1,3-oxazolidinyl, and 2-oxo-1,3-oxadinyl. Examples of partially saturated heteroaryl compounds that are substituted with oxo include 6-oxo-1,6-dihydropyridinyl, 6-oxo-1,1-dihydropyridazinyl, 2-oxo-1,2-dihydroquinolyl, 2-oxo-1,2-dihydroquinazolyl, and 1-oxo-1,2,3,4-tetrahydroisoquinolyl.

[0126] "Linear C 1-3 "Alkanediyl" refers to a divalent, linear hydrocarbon group formed by removing one hydrogen atom from an alkyl group having 1 to 3 carbon atoms. Examples include methanediyl, ethane-1,2-diyl, and propane-1,3-diyl.

[0127] "C 1-2 "Alkanediyl" refers to a divalent, linear hydrocarbon group formed by removing one hydrogen atom from an alkyl group having one or two carbon atoms. Examples include methanediyl, ethane-1,1-diyl, and ethane-1,2-diyl. "C 1-8 "Alkanediyl" refers to a divalent hydrocarbon group obtained by removing one hydrogen atom from an alkyl group having 1 to 8 carbon atoms. Examples include methanediyl, ethane-1,1-diyl, ethane-1,2-diyl, propane-1,1-diyl, propane-1,3-diyl, propane-2,2-diyl, butane-1,4-diyl, pentane-1,4-diyl, pentane-1,5-diyl, pentane-2,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, 2-methylbutane-1,4-diyl, 2-methylpentane-2,5-diyl, and 4-methylpentane-1,4-diyl. "C 2-7 "Alkanediyl" refers to a divalent hydrocarbon group obtained by removing one hydrogen atom from an alkyl group having 2 to 7 carbon atoms. Examples include ethane-1,1-diyl, ethane-1,2-diyl, propane-1,1-diyl, propane-1,3-diyl, propane-2,2-diyl, butane-1,4-diyl, pentane-1,4-diyl, pentane-1,5-diyl, pentane-2,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, 2-methylbutane-1,4-diyl, 2-methylpentane-2,5-diyl, and 4-methylpentane-1,4-diyl. 3-6"Alkanediyl" refers to a divalent hydrocarbon group obtained by removing one hydrogen atom from an alkyl group having 3 to 6 carbon atoms. Examples include propane-1,1-diyl, propane-1,3-diyl, propane-2,2-diyl, butane-1,4-diyl, pentane-1,4-diyl, pentane-1,5-diyl, pentane-2,5-diyl, hexane-1,6-diyl, 2-methylbutane-1,4-diyl, 2-methylpentane-2,5-diyl, and 4-methylpentane-1,4-diyl. "C 3-8 "Alkanediyl" refers to a divalent hydrocarbon group obtained by removing one hydrogen atom from an alkyl group having 3 to 8 carbon atoms. Examples include propane-1,1-diyl, propane-1,3-diyl, propane-2,2-diyl, butane-1,4-diyl, pentane-1,4-diyl, pentane-1,5-diyl, pentane-2,5-diyl, hexane-1,6-diyl, heptane-1,7-diyl, octane-1,8-diyl, 2-methylbutane-1,4-diyl, 2-methylpentane-2,5-diyl, and 4-methylpentane-1,4-diyl. "C4 alkanediyl" refers to a divalent hydrocarbon group obtained by removing one hydrogen atom from an alkyl group having four carbon atoms. An example is butane-1,4-diyl.

[0128] One preferred embodiment of the compound of the present invention is the following embodiment (A). Appearance (A): In the aforementioned equation [I]

[0129] [ka] In the compounds represented, their pharmaceutically acceptable salts, or their hydrates; X is carboxy, C 1-4 Alkoxycarbonyl, tetrazolyl, or group represented by the following formulas [II-2] to [II-5]

[0130] [ka] That is the case.

[0131] In this embodiment, W is a linear C 1-3 Alkanediyl or a structure selected from the following group of formulas [III]

[0132] [ka] And, Here, The linear C 1-3 Alkandiyl is C 1-6 Alkyl, Halo C 1-6 Alkyl, Phenylen C 1-3 Alkyl and pyridyl C 1-3 It may be substituted with one group selected from the group consisting of alkyl groups. And the linear C 1-3 If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A 1 , ring A 2 , and ring A 3 C 3-8 Cycloalkanes, partially saturated 9-10 membered fused hydrocarbon aromatic rings, 4-8 membered saturated heterocycles containing an oxygen atom, 4-8 membered saturated heterocycles containing a sulfur atom, or 4-8 membered saturated heterocycles containing a nitrogen atom. And, Here, The sulfur atom in the 4-8 member saturated heterocycle containing the sulfur atom may be substituted with 1-2 oxos. The nitrogen atom in the saturated heterocycle of 4 to 8 members containing the nitrogen atom is one C 1-4 It may be substituted with an alkylcarbonyl, Also, R A11 , R A21 , and R A31 These are, independently, a hydrogen atom, a hydroxyl atom, a halogen atom, and C 1-6 Alkyl, C 1-6An alkoxy or a saturated heterocycline with 4 to 6 members containing a nitrogen atom, R A12 , R A22 , and R A32 These are independently a hydrogen atom, a halogen atom, or a methyl atom. Also, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 These may each combine to form an oxo, moreover, R A11 and R A12 , R A21 and R A22 , and R A31 and R A32 Each of these atoms combines with the carbon atoms in the adjacent ring to form C 3-6 Cycloalkanes may be formed.

[0133] A more preferred W is a linear C 1-3 Alkanediyl or a structure selected from the following group of formulas [III]

[0134] [ka] And, Here, The linear C 1-3 Alkandiyl is C 1-4 Alkyl, Halo C2 alkyl, Phenylen C 1-2 It may be substituted with one group selected from the group consisting of alkyl and pyridyl C1alkyl groups. And the linear C 1-3 If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A 1 C 3-7A cycloalkane, a partially saturated 9-membered fused hydrocarbon aromatic ring, a 4-6 membered saturated heterocycle containing an oxygen atom, a 6-membered saturated heterocycle containing a sulfur atom, or a 4-6 membered saturated heterocycle containing a nitrogen atom, Here, The sulfur atom in the 6-membered saturated heterocycle containing the sulfur atom may be substituted with 1 or 2 oxos. The nitrogen atom in the 4-6 member saturated heterocycle containing the nitrogen atom may be substituted with one C1 alkylcarbonyl. Also, R A11 is a hydrogen atom, hydroxyl, halogen atom, C1 alkyl, C 1-3 An alkoxy or a 6-membered saturated heterocycline containing a nitrogen atom, R A12 is a hydrogen atom, a halogen atom, or a methyl atom, Also, R A11 and R A12 They may combine to form an oxo, moreover, R A11 and R A12 These may also form C4 cycloalkanes by combining with carbon atoms in adjacent rings. Ring A 2 It is a C3 cycloalkane or a 6-membered saturated heterocycle containing an oxygen atom, Here, R A21 It is a hydrogen atom, R A22 It is a hydrogen atom, Ring A 3 C 3-5 A cycloalkane, a partially saturated 9-membered fused hydrocarbon aromatic ring, or a 6-membered saturated heterocycle containing an oxygen atom, Here, R A31 It is a hydrogen atom, R A32 This is a hydrogen atom.

[0135] A more preferable W is methanediyl, propane-1,3-diyl, or a structure represented by the following formulas [III-1] to [III-3].

[0136] [ka] And, Here, The methanediyl may be substituted with one group selected from the group consisting of methyl, n-butyl, haloethyl, benzyl, phenethyl, and pyridylmethyl. Furthermore, if the methanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A 1 These are cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, dihydroindene, oxetane, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, azetidine, pyrrolidine, or piperidine. Here, The sulfur atom in the tetrahydrothiopyran may be substituted with two oxos. The nitrogen atoms in the azetidine, pyrrolidine, and piperidine may be substituted with one methylcarbonyl atom. Also, R A11 is a hydrogen atom, hydroxyl, fluorine atom, methyl, methoxy, ethoxy, isopropoxy, or morpholinyl. R A12 is a hydrogen atom, a fluorine atom, or a methyl atom, Also, R A11 and R A12 They may combine to form an oxo, moreover, R A11 and R A12 These may each combine with carbon atoms in adjacent rings to form cyclobutane. Ring A 2It is cyclopropane or tetrahydropyran, Here, R A21 It is a hydrogen atom, R A22 It is a hydrogen atom, Ring A 3 These are cyclopropane, cyclobutane, cyclopentane, dihydroindene, or tetrahydropyran. Here, R A31 It is a hydrogen atom, R A32 This is a hydrogen atom.

[0137] R 1 This is a hydrogen atom.

[0138] R 2 C 6-10 Alkyl groups, or groups represented by the following formulas [IV-1] or [IV-2]

[0139] [ka] And, Here, Ring B 1 C 3-8 A cycloalkyl, phenyl, or 5-6 member heteroaryl containing a nitrogen atom, R B11 and R B12 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It is an alkoxy, L 1 C 3-8 Alkanedil (the C 3-8 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) The structure represented by formula [V-6]:-CH2CH2CH=C(CH3)- or the structure represented by the following formula [V-1]

[0140] [ka] And, Here, n11 is an integer between 0 and 3. n12 is an integer between 0 and 5. n13 is an integer between 0 and 3. Also, C 3-8 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L11 )- can be replaced with, R L1 C 1-3 It is alkyl, Ring B 2 This is a partially saturated 9-10 membered fused aryl ring, or a partially saturated 9-10 membered fused heteroaryl ring containing a nitrogen atom. R B1 and R B2 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It is an alkoxy, L 2 C 1-2 Alkanedil (the C 1-2 The alkanediyl may be substituted with 1 to 4 fluorine atoms.

[0141] A more preferred R 2 C 7-8 Alkyl or groups represented by the following formulas [IV-1] or [IV-2]

[0142] [ka] And, Here, Ring B 1 It is a C6 cycloalkyl, phenyl, or 6-membered heteroaryl containing a nitrogen atom, R B11 and R B12These are independently a hydrogen atom, a halogen atom, a C1 alkyl, or a C1 alkoxy. L 1 C 3-5 Alkanedil (the C 3-5 The alkanediyl may be substituted with 1 or 2 fluorine atoms. ) The structure represented by formula [V-6]:-CH2CH2CH=C(CH3)- or the structure represented by the following formula [V-1]

[0143] [ka] And, Here, n1 is an integer between 0 and 1. n2 is 1, n3 is an integer between 0 and 1. Also, C 3-5 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded is defined as -O-, -S-, or -N(R L1 )- can be replaced with, R L1 It is a C1 alkyl group, Ring B 2 This is a partially saturated 9-membered fused aryl, or a partially saturated 9-membered fused heteroaryl containing a nitrogen atom. R B1 and R B2 They are identically hydrogen atoms, L 2 It is C2 alkanediyl.

[0144] A more preferable R 2 isoheptyl, isooctyl, or a group represented by the following formulas [IV-1] or [IV-2]

[0145] [ka] And, Here, Ring B 1 These are cyclohexyl, phenyl, or pyridyl, R B11 and R B12 L is independently a hydrogen atom, a fluorine atom, a methyl atom, or a methoxy atom. 1 The structure is represented by the following equations [V-3]~[V-12], [V-14]~[V-19].

[0146] [ka]

[0147] [ka] It is one of the following: Here, n4 is an integer between 3 and 5. n12' is 1, n12" is 1, Ring B 2 It is dihydroindenyl or isoindlinyl, R B1 and R B2 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0148] [ka] And, Here, n5 is 2 That is the case.

[0149] R 3 is a hydrogen atom or C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. A more preferred R 3 is a hydrogen atom or C 1-2 Alkyl (the C 1-2 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. A more preferable R 3 is a hydrogen atom, methyl (the methyl group may be substituted with one group selected from the group consisting of hydroxy and methoxy), or ethyl.

[0150] R 4 The base is represented by the following formula [VI]

[0151] [ka] And, Here, Ring C is a phenyl, a 6-membered heteroaryl containing a nitrogen atom, or a 9-10 membered fused ring heteroaryl. The phenyl contains a halogen atom, C 1-6 Alkyl, C 1-6 Alkoxy, and C 1-6 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carbamoyl, cyano, halogen atom, C 1-6 Alkyl (the C 1-6 Alkyl is hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C 1-6 alkyl (the halo C 1-6 The alkyl group may be substituted with one hydroxyl group. 2-6 Alkenil, C 3-8 Cycloalkyl (the C 3-8 The cycloalkyl group may be substituted with one hydroxyl group. 1-6 Alkoxy, Halo C 1-6 Alkoxy, C 3-8 Cycloalkoxy, C 1-6 Alkyl sulfinyl, C 1-6 Alkyl sulfonyl, mono C 1-6Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylcarbonyl, Halo C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl and mono-C 1-6 They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkylaminocarbonyl groups. The six-membered heteroaryl containing the nitrogen atom has one C 1-6 Substituted with alkoxy, and further, Cyano and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. The 9-10 member fused ring heteroaryl is C 1-6 Alkyl or C 1-6 It may be substituted with one or two groups selected identically or differently from the group consisting of alkoxys. A more preferred R 4 The base is represented by the following formula [VI]

[0152] [ka] And, Here, Ring C is a phenyl, a 6-membered heteroaryl containing a nitrogen atom, or a 9-10 membered fused ring heteroaryl. The phenyl contains a halogen atom, C 1-3 Alkyl, C 1-3 Alkoxy, and C 1-2 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carbamoyl, cyano, halogen atom, C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and C1 alkoxy. ), halo-C2 alkyl (the halo-C2 alkyl group may be substituted with one hydroxyl group), C 2-3 Alkenyl, C3 cycloalkyl (the C3 cycloalkyl may be substituted with one hydroxyl group), C1-3 Alkoxy, HaloC2 alkoxy, C3 cycloalkoxy, C1 alkylsulfinyl, C1 alkylsulfonyl, MonoC2 alkylamino, DiC 1-2 Alkylamino, C 1-2 It may be substituted with 1 to 3 groups selected identically or differently from the group consisting of alkylcarbonyl, haloC1alkylcarbonyl, C1alkoxycarbonyl, and monoC1alkylaminocarbonyl. The six-membered heteroaryl containing the nitrogen atom has one C 1-2 Substituted with alkoxy, and further, Cyano and C 1-2 It may be substituted with one group selected from the group consisting of alkoxys. The 9-10 member fused ring heteroaryl is C 2-3 The group may be substituted with one or two groups selected identically or differently from the group consisting of alkyl or C2 alkoxy groups. A more preferable R 4 The base is represented by the following formula [VI]

[0153] [ka] And, Here, Ring C is phenyl, pyridyl, pyrimidinyl, indolyl, indazolyl, benzimidazolyl, pyrazolopyridyl, dihydrobenzofuranyl, or dihydroindolyl. The phenyl is substituted with one group selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, methylcarbonyl, and ethylcarbonyl, and further, They may be substituted with 1 to 4 groups selected identically or differently from the group consisting of hydroxy, carbamoyl, cyano, fluorine, chlorine, bromine, methyl, ethyl, n-propyl, isopropyl (methyl, ethyl, n-propyl, and isopropyl may be substituted with one group selected from the group consisting of hydroxy and methoxy), haloethyl (haloethyl may be substituted with one hydroxyl), ethenyl, isopropenyl, cyclopropyl (cyclopropyl may be substituted with one hydroxyl), methoxy, ethoxy, n-propoxy, isopropoxy, haloethoxy, cyclopropoxy, methylsulfinyl, methylsulfonyl, ethylamino, ethylmethylamino, diethylamino, methylcarbonyl, ethylcarbonyl, halomethylcarbonyl, methoxycarbonyl, and methylaminocarbonyl. The pyridyl, pyrimidinyl is substituted with one methoxy or ethoxy molecule, and further, It may be substituted with one group selected from the group consisting of cyano and ethoxy. The pyrimidinyl may be substituted with one methoxy group, and may also be substituted with one more methoxy group. The indolyl, indazolyl, benzimidazolyl, pyrazolopyridyl, dihydrobenzofuranyl, or dihydroindolyl may be substituted with one or two groups selected identically or differently from the group consisting of ethyl, n-propyl, or ethoxy.

[0154] Also, R 3 and R 4 However, when they come together with adjacent carbon atoms to form a fused ring, Preferred ring fusions are a partially saturated 9-10 membered fused hydrocarbon aromatic ring (the partially saturated 9-10 membered fused hydrocarbon aromatic ring may be substituted with 1-2 halogen atoms) or a partially saturated 9-10 membered fused heteroaromatic ring containing an oxygen atom (the partially saturated 9-10 membered fused heteroaromatic ring containing an oxygen atom may be substituted with 1-2 halogen atoms). A more preferred ring fusion is a partially saturated nine-membered fused hydrocarbon aromatic ring (the partially saturated nine-membered fused hydrocarbon aromatic ring may be substituted with one or two halogen atoms) or a partially saturated nine-membered fused heteroaromatic ring containing an oxygen atom (the partially saturated nine-membered fused heteroaromatic ring containing an oxygen atom may be substituted with one or two halogen atoms). A more preferred ring fusion is dihydroindene (which may be substituted with 1-2 halogen atoms) or dihydrobenzofuran (which may be substituted with 1-2 halogen atoms). That is the case.

[0155] Another preferred embodiment of the compound of the present invention is the following embodiment (B). Mode (B): In the compound represented by the above formula [I], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I] is the same as the compound represented by formula [I-1] below.

[0156] [ka] And, Here, R 2 This is a base represented by the following formula [IV-1] or [IV-2]

[0157] [ka] That is the case. In this manner, X is carboxy, C 1-4 It is an alkoxycarbonyl or tetrazolyl compound. One more preferred X is carboxyl or tetrazolyl, In this case, one even more preferred X is carboxyl, In this case, another even more preferred X is tetrazolyl, Other more preferred X is C 1-4 It is an alkoxycarbonyl, In this case, one even more preferred X is a C1 alkoxycarbonyl, In this case, another even more preferred X is a C2 alkoxycarbonyl, In this case, another even more preferred X is a C4 alkoxycarbonyl.

[0158] W is methanediyl or a structure represented by the following formula [III-1]

[0159] [ka] And, Here, The methanediyl is C 1-6 Alkyl (the C 1-6 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl. 1-6 Alkyl, C 3-8 Cycloalkyl, phenyl C 1-3 Alkyl and pyridyl C 1-3 It may be substituted with one group selected from the group consisting of alkyl groups. Furthermore, if the methanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Also, In the structure represented by formula [III-1], Preferred ring A 1 C 3-8 A cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, or a 4-8 membered saturated heterocycle containing a nitrogen atom, Here, The sulfur atom in the 4-8 member saturated heterocycle containing the sulfur atom may be substituted with 1-2 oxos. Also, The nitrogen atom in the saturated heterocycle of 4 to 8 members containing the nitrogen atom is C 1-4 Alkylcarbonyl and C 1-4 It may be substituted with one group selected from the group consisting of alkoxycarbonyls. Preferred R A11 These are hydrogen atoms, hydroxyl, carboxyl, halogen atoms, and C 1-6 Alkyl, C 1-6 Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl. Preferred R A12 is a hydrogen atom, a halogen atom, or a methyl atom, Also, R A11 and R A12 They may combine to form an oxo, moreover, R A11 and R A12 Each of these atoms combines with the carbon atoms in the adjacent ring to form C 3-6 Cycloalkanes may be formed.

[0160] A more preferred W is methanediyl or a structure represented by the following formula [III-1].

[0161] [ka] And, Here, The methanediyl is C 1-4 Alkyl (the C 1-4 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl groups. ), halo-C2 alkyl, phenyl-C 1-2 It may be substituted with one group selected from the group consisting of alkyl and pyridyl C1alkyl groups. Furthermore, if the methanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Also, In the structure represented by formula [III-1], Preferred ring A 1 C 3-7 A cycloalkane, a partially saturated 9-membered fused hydrocarbon aromatic ring, a 4-6 membered saturated heterocycle containing an oxygen atom, a 6-membered saturated heterocycle containing a sulfur atom, or a 4-6 membered saturated heterocycle containing a nitrogen atom, Here, The sulfur atom in the 6-membered saturated heterocycle containing the sulfur atom may be substituted with 1 or 2 oxos. Also, The nitrogen atom in the 4-6 member saturated heterocycle containing the nitrogen atom may be substituted with one group selected from the group consisting of C1 alkylcarbonyls. Preferred R A11 teeth, Hydrogen atom, hydroxyl, carboxyl, halogen atom, C1 alkyl, C 1-3 An alkoxy, or a 5-6 member saturated heterocycline containing a nitrogen atom (the 5-6 member saturated heterocycline containing a nitrogen atom may be substituted with one C1 alkyl group), Preferred R A12 is a hydrogen atom, a halogen atom, or a methyl atom, Also, R A11 and R A12 They may combine to form an oxo, moreover, R A11 and R A12 These may each combine with a carbon atom in an adjacent ring to form a C4 cycloalkane.

[0162] A more preferred W is methanediyl or a structure represented by the following formula [III-1].

[0163] [ka] And, Here, The methanediyl may be substituted with one group selected from the group consisting of methyl (the methyl may be substituted with one group selected from the group consisting of hydroxy and carboxy), ethyl, n-butyl, isobutyl, haloethyl, benzyl, phenethyl, and pyridylmethyl. Furthermore, if the methanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Also, In the structure represented by formula [III-1], Preferred ring A 1 These are cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, dihydroindene, oxetane, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, azetidine, pyrrolidine, or piperidine. Here, The sulfur atom in the tetrahydrothiopyran may be substituted with two oxos. Also, The nitrogen atoms in the azetidine, pyrrolidine, and piperidine may be substituted with one methylcarbonyl atom. Preferred R A11 teeth, A hydrogen atom, a hydroxyl atom, a carboxyl atom, a fluorine atom, a methyl atom, a methoxy atom, an ethoxy atom, an isopropoxy atom, a pyrrolidinyl atom, a morpholinyl atom, or a piperazinyl atom (the piperazinyl atom may be substituted with one methyl atom). Preferred R A12 is a hydrogen atom, a fluorine atom, or a methyl atom, Also, R A11 and R A12 They may combine to form an oxo, moreover, R A11 and R A12 These may each combine with carbon atoms in adjacent rings to form cyclobutane.

[0164] Ring B 1 It is phenyl, RB11 and R B12 These are, independently, hydrogen atoms, halogen atoms, and C 1-6 Alkyl, or C 1-6 It is an alkoxy, L 1 C 3-8 Alkanedil (the C 3-8 The alkanediyl may be substituted with 1 to 5 fluorine atoms. Also, C 3-8 R is one of the carbon atoms in alkanediyl. 2 Atoms that are two or more atoms away from the nitrogen atom to which the compound is bonded may be replaced by the compound -O-. Ring B 2 These are partially saturated 9-10 membered fused aryl rings, or 9-10 membered fused heteroaryl rings containing a nitrogen atom. R B21 and R B22 They are identically hydrogen atoms, L 2 C 1-2 Alkanedil (the C 1-2 The alkanediyl may be substituted with 1 to 4 fluorine atoms.

[0165] A more preferred ring B 1 It is phenyl, R B11 and R B12 These are independently a hydrogen atom, a halogen atom, a C1 alkyl, or a C1 alkoxy. L 1 C 3-6 Alkanedil (the C 3-6 The alkanediyl may be substituted with 1-2 fluorine atoms. Also, C 3-6 R is one of the carbon atoms in alkanediyl. 2 Atoms that are two or more atoms away from the nitrogen atom to which the compound is bonded may be replaced by the compound -O-. A more preferred ring B 2This is a partially saturated 9-membered fused aryl, or a 9-membered fused heteroaryl containing a nitrogen atom. R B21 and R B22 They are identically hydrogen atoms, L 2 C 1-2 It is Arcanziel.

[0166] A more preferred ring B 1 It is phenyl, R B11 and R B12 These are independently a hydrogen atom, a fluorine atom, a methyl atom, or a methoxy atom. L 1 The structure is represented by the following equations [V-3]~[V-5], [V-7]~[V-8], [V-11]~[V-12], [V-14]~[V-16].

[0167] [ka]

[0168] [ka] It is one of the following: Here, n4 is an integer between 3 and 5. A more preferred ring B 2 These are dihydroindenyl, indolyl, or isoindlinyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0169] [ka] And, Here, n5 is an integer between 1 and 2.

[0170] R 3 C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. A more preferred R 3 is methyl (the methyl group may be substituted with one group selected from the group consisting of hydroxy and methoxy) or ethyl, A more preferable R 3 It is methyl Particularly preferred R 3 This is the stereochemical configuration represented by the following equation [VII].

[0171] [ka] It is methyl.

[0172] R 4 The base is represented by the following formula [VI]

[0173] [ka] And, Here, The carbon atom of the ring is phenyl. Here, The phenyl contains a halogen atom, C 1-6 Alkyl, C 1-6 Alkoxy, and C 1-6 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C 1-6 Alkyl (the C 1-6 Alkyl is hydroxy and C 1-6 It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C 1-6 alkyl (the halo C 1-6 The alkyl group may be substituted with one hydroxyl group.2-6 Alkenil, C 2-6 Alkinyl, C 3-8 Cycloalkyl (the C 3-8 The cycloalkyl group may be substituted with one hydroxyl group. 1-6 Alkoxy, Halo C 1-6 Alkoxy, C 3-8 Cycloalkoxy, C 1-6 Alkyl sulfanyl, C 1-6 Alkyl sulfinyl, C 1-6 Alkyl sulfonyl, mono C 1-6 Alkylamino, diC 1-6 Alkylamino, C 1-6 Alkylcarbonyl, Halo C 1-6 Alkylcarbonyl, C 1-6 Alkoxycarbonyl, monoC 1-6 Alkylaminocarbonyl and diC 1-6 The group may be substituted with 1 to 4 groups selected identically or differently from the group consisting of alkylaminocarbonyl groups.

[0174] A more preferred R 4 The base is represented by the following formula [VI]

[0175] [ka] And, Here, The carbon atom of the ring is phenyl. Here, The phenyl contains a halogen atom, C 1-3 Alkyl, C 1-3 Alkoxy, and C 1-2 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and C1 alkoxy groups. 1-2 alkyl (the halo C 1-2The alkyl group may be substituted with one hydroxyl group. 2-3 Alkenyl, C3 cycloalkyl (the C3 cycloalkyl may be substituted with one hydroxyl group), C 1-3 Alkoxy, HaloC2 alkoxy, C3 cycloalkoxy, C1 alkylsulfinyl, C1 alkylsulfonyl, MonoC2 alkylamino, DiC2 alkylamino, C 1-2 The group may be substituted with 1 to 4 groups, either identically or differently, selected from the group consisting of alkylcarbonyl, halo-C1 alkylcarbonyl, C1 alkoxycarbonyl, and mono-C1 alkylaminocarbonyl.

[0176] A more preferable R 4 The base is represented by the following formula [VI]

[0177] [ka] And, Here, The carbon atom of the ring is phenyl. Here, The phenyl is substituted with one group selected from the group consisting of a fluorine atom, a chlorine atom, a bromine atom, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, n-propoxy, isopropoxy, methylcarbonyl, and ethylcarbonyl, and further, They may be substituted with 1 to 4 groups, either identically or differently, selected from the group consisting of hydroxy, carboxy, carbamoyl, cyano, fluorine, chlorine, bromine, methyl (methyl may be substituted with one group selected from the group consisting of hydroxy and methoxy), ethyl, n-propyl, isopropyl (ethyl, n-propyl, and isopropyl may be substituted with one hydroxyl), halomethyl, haloethyl (haloethyl may be substituted with one hydroxyl), ethenyl, isopropenyl, cyclopropyl (cyclopropyl may be substituted with one hydroxyl), methoxy, ethoxy, n-propoxy, isopropoxy, haloethoxy, cyclopropoxy, methylsulfinyl, methylsulfonyl, monoethylamino, diethylamino, methylcarbonyl, ethylcarbonyl, halomethylcarbonyl, methoxycarbonyl, and methylaminocarbonyl.

[0178] Another preferred embodiment of the compound of the present invention is the following embodiment (C). Appearance (C):

[0179] In this embodiment (C), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the compound represented by the following formula [I-2]

[0180] [ka] And, Here, R 2 This is a base represented by the following formula [IV-1] or [IV-2]

[0181] [ka] and; Here, W, ring B 1 , R B11 , R B12 , L 1 , ring B 2 , R B21 , R B22 , L 2 , and R 4 As stated above.

[0182] In this embodiment (C), a more preferred embodiment is as follows: In the above formula [I-2], W is methanediyl or a structure represented by formula [III-1] above.

[0183] [ka] And, Here, The methanediyl may be substituted with one methyl group. Furthermore, it may be substituted with one methyl group. Also, In the structure represented by formula [III-1], Ring A 1 C 3-4 A cycloalkane or a saturated heterocycle with 4-5 members containing an oxygen atom, R A11 is a hydrogen atom, hydroxyl, halogen atom, C1 alkyl, or C 1-2 It is an alkoxy, R A12 is a hydrogen atom, a halogen atom, or a methyl atom;

[0184] Ring B 1 It is phenyl, R B11 and R B12 It is also a hydrogen atom, L 1 C 3-5 Alkanedil (the C 3-5The alkanediyl may be substituted with 1-2 fluorine atoms. Here, C 3-5 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded may be replaced by the -O- formula. Ring B 2 It is a partially saturated 9-membered fused ring aryl, R B21 and R B22 It is also a hydrogen atom; L 2 It is a C2 alkanediyl;

[0185] R 4 The base is represented by the following formula [VI]

[0186] [ka] And, Here, The carbon ring is phenyl, The phenyl contains a halogen atom, C 1-3 Alkyl, C 1-2 It is substituted with one group selected from the group consisting of alkoxys and C1 alkylcarbonyls, and further, Cyano, halogen atom, C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one hydroxyl group. ), C2 alkenyl, C3 cycloalkyl, C 1-2 The group may be substituted with 1 to 4 groups, either identically or differently, selected from the group consisting of alkoxy, monoC2 alkylamino, and C1 alkylcarbonyl.

[0187] In this embodiment (C), a more preferred embodiment is as follows: In the above formula [I-2], W has a structure represented by the following equations [III-4] to [III-17].

[0188] [ka] It is either one of the following; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formulas [V-3], [V-8], [V-12], [V-14], or [V-15].

[0189] [ka] And, Here, n4 is an integer between 3 and 4. Ring B 2 It is dihydroindenyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0190] [ka] And, Here, n5 is 2; R 4 This is the base represented by the following formulas [VI-1] to [VI-21].

[0191] [ka]

[0192] [ka]

[0193] [ka] It is one of the following:

[0194] Another preferred embodiment of the compound of the present invention is the following embodiment (D). Pattern (D):

[0195] In this embodiment (D), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-3] below.

[0196] [ka] And, Here, R 2 This is a base represented by the following formula [IV-1] or [IV-2]

[0197] [ka] and; Here, W, ring B 1 , R B11 , R B12 , L 1 , ring B 2 , R B21 , R B22 , L 2 , and R 4 As stated above.

[0198] In this embodiment (D), a more preferred embodiment is as follows: In the above equation [I-3], W is methylene or the structure represented by the formula [III-1]

[0199]

Chemical formula

[0200] Ring B 1 is phenyl R B11 and R B12 are simultaneously hydrogen atoms L 1 is C 4-5 alkanediyl (the C 4-5 alkanediyl may be substituted with two fluorine atoms.) Also C 4-5 one of the carbon atoms in the alkanediyl that is two or more atoms away from the nitrogen atom to which R 2 is attached may be replaced with the formula -O- Ring B 2 is a partially saturated 9-member fused-ring aryl R B21 and R B22 are simultaneously hydrogen atoms L 2 is C2 alkanediyl;

[0201] R4 is a group represented by the following formula [VI]

[0202]

Chemical formula

[0203] In this embodiment (D), a more preferred embodiment is as follows. In the above formula [I-3], W is a structure represented by the following formula [III-4] to [III-11], [III-13] to [III-14], or [III-18] to [III-19]

[0204]

Chemical formula

[0205]

Chemical formula

[0206] [ka] And, Here, n5 is 2; R 4 This is a base represented by the following formulas [VI-2], [VI-3], [VI-8], [VI-10] to [VI-12], [VI-16], [VI-19], or [VI-21].

[0207] [ka]

[0208] [ka] It is one of the following:

[0209] Another preferred embodiment of the compound of the present invention is the following embodiment (E). Mode (E):

[0210] In this embodiment (E), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-4] below.

[0211] [ka] And, Here, R 4 The base is represented by the following formula [VI-22]

[0212] [ka] And, The group represented by formula [VI-22] consists of 1 to 2 C 1-6 It is substituted with alkoxy; Preferred W, ring B 1 , R B11 , R B12 , and L 1 As stated above.

[0213] In this embodiment (E), a more preferred embodiment is as follows: In the above formula [I-4], W is a structure represented by the following formula [III-1]

[0214] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 It is a C4 cycloalkane, R A11 C 1-2 It is an alkoxy, R A12 is a hydrogen atom; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 It is C5 alkanediyl, One of the carbon atoms in the C5 alkanediyl is R 2 Any atom that is two or more atoms away from the nitrogen atom to which it is bonded may be replaced by the -O- atom; R 4 The base represented by the above formula [VI-22] is

[0215] [ka] And, Here, The group represented by formula [VI-22] is substituted with two C2 alkoxy groups.

[0216] In this embodiment (E), a more preferred embodiment is as follows: In the above formula [I-4], W has a structure represented by the following equations [III-8] to [III-11].

[0217] [ka] and; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formula [V-14].

[0218] [ka] and; R 4 The base is represented by the following formula [VI-6]

[0219] [ka] That is the case.

[0220] And in this embodiment (E), one particularly preferred embodiment is as follows: The compound represented by the aforementioned formula [I-4] is one of the following:

[0221] [ka]

[0222] Furthermore, in this embodiment (E), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-4] is as follows:

[0223] [ka]

[0224] Furthermore, in this embodiment (E), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-4] is as follows:

[0225] [ka]

[0226] Furthermore, in this embodiment (E), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-4] is as follows:

[0227] [ka]

[0228] Furthermore, in this embodiment (E), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-4] is as follows:

[0229] [ka]

[0230] Another preferred embodiment of the compound of the present invention is the following embodiment (F). Mode (F):

[0231] In this embodiment (F), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-5] below.

[0232] [ka] And, Here, W, L 2 , and R 4 As stated above.

[0233] In this embodiment (F), a more preferred embodiment is as follows: In the above formula [I-5], W is a structure represented by the following formula [III-1]

[0234] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 It is a C4 cycloalkane, R A11 It is a C1 alkoxy, R A12 is a hydrogen atom; L2 It is a C2 alkanediyl; R 4 The base is represented by the following formula [VI]

[0235] [ka] And, Here, The carbon ring is phenyl, The phenyl is substituted with three groups, identically or differently selected from the group consisting of C2 alkoxys and C1 alkylcarbonyls, and further, It may be substituted with a single C1 alkyl group.

[0236] In this embodiment (F), a more preferred embodiment is as follows: In the above formula [I-5], W is a structure represented by the following formula [III-8] or [III-9].

[0237] [ka] and; L 2 The structure is represented by the following formula [V-20].

[0238] [ka] And, Here, n5 is 2; R 4 This is a base represented by the following formula [VI-10] or [VI-12].

[0239] [ka] That is the case.

[0240] And in this embodiment (F), one particularly preferred embodiment is as follows: The compound represented by the above formula [I-5] is one of the following:

[0241] [ka]

[0242] Furthermore, in this embodiment (F), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-5] is as follows:

[0243] [ka]

[0244] Furthermore, in this embodiment (F), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-5] is as follows:

[0245] [ka]

[0246] Furthermore, in this embodiment (F), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-5] is as follows:

[0247] [ka]

[0248] Furthermore, in this embodiment (F), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-5] is as follows:

[0249] [ka]

[0250] Another preferred embodiment of the compound of the present invention is the following embodiment (F-2). Appearance (F-2):

[0251] In this embodiment (F-2), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-5-2] below.

[0252] [ka] And, Here, R 4 The base is represented by the following formula [VI-26]

[0253] [ka] And, The group represented by formula [VI-26] is C 1-6 Alkyl, C 3-8 Cycloalkyl, and C 1-6 It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Halogen atoms and C 1-6 It may be substituted with one group selected from the group consisting of alkyl groups; W is as described above.

[0254] In this embodiment (F-2), a more preferred embodiment is as follows: In the above formula [I-5-2], W is a structure represented by the following formula [III-1]

[0255] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 It is a C4 cycloalkane, R A11 C 1-2 It is an alkoxy, R A12 is a hydrogen atom; R 4 The base represented by the above formula [VI-26] is

[0256] [ka] And, Here, The group represented by formula [VI-26] is substituted with one group selected from the group consisting of C1 alkyl, C3 cycloalkyl, and C1 alkylcarbonyl, and further, It may be substituted with one group selected from the group consisting of halogen atoms and C1 alkyl groups.

[0257] In this embodiment (F-2), a more preferred embodiment is as follows: In the above formula [I-5-2], W is a structure represented by the following formula [III-8] or [III-10]

[0258] [ka] and; R 4 This is a base represented by the following formulas [VI-2], [VI-6], [VI-10] to [VI-12], [VI-27], or [VI-28].

[0259] [ka] That is the case.

[0260] Furthermore, in this embodiment (F-2), particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-5-2] is as follows:

[0261] [ka]

[0262] Another preferred embodiment of the compound of the present invention is the following embodiment (G). Mode (G):

[0263] In this embodiment (G), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-6] below.

[0264] [ka] And, Here, R 4 The base is represented by the following formula [VI-23]

[0265] [ka] And, The group represented by formula [VI-23] is one C 1-6 Substituted with alkylcarbonyl, and further, It may be substituted with one halogen atom; W, ring B1 , R B11 , R B12 , and L 1 is as described above.

[0266] In this aspect (G), a more preferred aspect is as follows. In the formula [I-6], W is a structure represented by the following formula [III-1]

[0267] [Chemical formula] and Here, in the structure represented by the formula [III-1], ring A 1 is a C4 cycloalkane, R A11 is C 1-2 alkoxy, R A12 is a hydrogen atom; ring B 1 is phenyl, R B11 and R B12 are identically a hydrogen atom, L 1 is C 4-5 alkanediyl, one of the carbon atoms in the C 4-5 alkanediyl that is two or more atoms away from the nitrogen atom to which R 2 is attached may be replaced by the formula -O-; R 4 is a group represented by the formula [VI-23]

[0268] [Chemical formula] and Here, The group represented by formula [VI-23] is substituted with one C1 alkylcarbonyl, and further, It may be substituted with a single halogen atom.

[0269] In this embodiment (G), a more preferred embodiment is as follows: In the above formula [I-6], W is a structure represented by the following formula [III-8] or [III-10]

[0270] [ka] and; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formula [V-12] or [V-14].

[0271] [ka] and; R 4 This is a base represented by the following formula [VI-24] or [VI-25].

[0272] [ka] That is the case.

[0273] And in this embodiment (G), one particularly preferred embodiment is as follows: The compound represented by the aforementioned formula [I-6] is one of the following:

[0274] [ka]

[0275] [ka]

[0276] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0277] [ka]

[0278] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0279] [ka]

[0280] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0281] [ka]

[0282] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0283] [ka]

[0284] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0285] [ka]

[0286] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0287] [ka]

[0288] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0289] [ka]

[0290] Furthermore, in this embodiment (G), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6] is as follows:

[0291] [ka]

[0292] Another preferred embodiment of the compound of the present invention is the following embodiment (G-2). Appearance (G-2):

[0293] In this embodiment (G-2), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-6-2] below.

[0294] [ka] And, Here, R 4 The base is represented by the following formula [VI-29]

[0295] [ka] And, The group represented by formula [VI-29] consists of a halogen atom and C 1-6 It is substituted with one group selected from the group consisting of alkyl groups; W is as described above.

[0296] In this embodiment (G-2), a more preferred embodiment is as follows: In the above formula [I-6-2], W is a structure represented by the following formula [III-1]

[0297] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 It is a C4 cycloalkane, R A11 is a hydrogen atom, a halogen atom, or C 1-2 It is an alkoxy, R A12 is a hydrogen atom or a halogen atom; R 4 The base represented by the above formula [VI-29] is

[0298] [ka] And, Here, The group represented by formula [VI-29] is substituted with one group selected from the group consisting of halogen atoms and C1 alkyl groups.

[0299] In this embodiment (G-2), a more preferred embodiment is as follows: In the above formula [I-6-2], W has a structure represented by the following formulas [III-6], [III-8] to [III-11], or [III-13].

[0300] [ka] and; R 4 This is a base represented by the following formula [VI-30] or [VI-31]

[0301] [ka] That is the case.

[0302] Furthermore, in this embodiment (G-2), one particularly preferred embodiment is as follows: The compound represented by the aforementioned formula [I-6-2] is one of the following:

[0303] [ka]

[0304] [ka]

[0305] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0306] [ka]

[0307] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0308] [ka]

[0309] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0310] [ka]

[0311] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0312] [ka]

[0313] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0314] [ka]

[0315] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0316] [ka]

[0317] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0318] [ka]

[0319] Furthermore, in this embodiment (G-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-6-2] is as follows:

[0320] [ka]

[0321] Another preferred embodiment of the compound of the present invention is the following embodiment (H). Mode (H):

[0322] In this embodiment (H), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-7] below.

[0323] [ka] And, Here, R 2 This is a base represented by the following formula [IV-1] or [IV-2]

[0324] [ka] and; X, W, ring B 1 , R B11 , R B12 , L 1 , ring B 2 , R B21 , R B22 , L 2 , and R 4 As stated above.

[0325] In this embodiment (H), a more preferred embodiment is as follows: In the above formula [I-7], X is a carboxyl or tetrazolyl;

[0326] W is a structure represented by the following formula [III-1]

[0327] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 teeth, C3-4 It is a cycloalkane, R A11 teeth, Hydrogen atom, halogen atom, or C 1-2 It is an alkoxy, R A12 teeth, It is a hydrogen atom or a halogen atom;

[0328] Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 C 4-5 Alkanedil (the C 4-5 The alkanediyl may be substituted with two fluorine atoms. Also, C 4-5 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded may be replaced by the -O- formula. Ring B 2 It is a partially saturated 9-membered fused ring aryl, R B21 and R B22 They are identically hydrogen atoms, L 2 It is a C2 alkanediyl;

[0329] R 4 The base is represented by the following formula [VI]

[0330] [ka] And, Here, The carbon ring is phenyl, The phenyl contains a halogen atom, C 1-3 Alkyl, C 1-2 It is substituted with one group selected from the group consisting of alkoxys and C1 alkylcarbonyls, and further, Halogen atom, C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one hydroxyl group. 1-2 The group may be substituted with 1 to 3 groups selected identically or differently from the group consisting of alkoxy and C1 alkylcarbonyl groups.

[0331] In this embodiment (H), a more preferred embodiment is as follows: In the above formula [I-7], X is a carboxyl or tetrazolyl; W is a structure represented by the following formulas [III-5], [III-8] to [III-11], or [III-13].

[0332] [ka] and; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formulas [V-3], [V-12], or [V-14].

[0333] [ka] And, Here, n4 is an integer of 4, Ring B 2 It is dihydroindenyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0334] [ka] And, Here, n5 is 2; R 4 This is a base represented by the following formulas [VI-2], [VI-7], [VI-8], [VI-10], [VI-11], or [VI-12].

[0335] [ka] That is the case.

[0336] And in this embodiment (H), One particularly preferred embodiment is that the compound represented by the aforementioned formula [I-7] is This is the case if any of the following apply:

[0337] [ka]

[0338] [ka]

[0339] [ka]

[0340] [ka]

[0341] [ka]

[0342] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0343] [ka]

[0344] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0345] [ka]

[0346] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0347] [ka]

[0348] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0349] [ka]

[0350] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0351] [ka]

[0352] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0353] [ka]

[0354] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0355] [ka]

[0356] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0357] [ka]

[0358] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0359] [ka]

[0360] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0361] [ka]

[0362] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0363] [ka]

[0364] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0365] [ka]

[0366] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0367] [ka]

[0368] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0369] [ka]

[0370] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0371] [ka]

[0372] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0373] [ka]

[0374] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0375] [ka]

[0376] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0377] [ka]

[0378] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0379] [ka]

[0380] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0381] [ka]

[0382] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0383] [ka]

[0384] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0385] [ka]

[0386] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0387] [ka]

[0388] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0389] [ka]

[0390] Furthermore, in this embodiment (H), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0391] [ka]

[0392] Another preferred embodiment of the compound of the present invention is the following embodiment (H-2). Appearance (H-2):

[0393] In this embodiment (H-2), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-7] below.

[0394] [ka] And, Here, R 2 The base is represented by the following formula [IV-1]

[0395] [ka] And, X, W, ring B 1 , R B11 , R B12 , L 1 , and R 4 As stated above.

[0396] In this embodiment (H-2), a more preferred embodiment is as follows: In the above formula [I-7], X is a carboxyl;

[0397] W is a structure represented by the following formula [III-1]

[0398] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 teeth, C 3-4 It is a cycloalkane, R A11 teeth, Hydrogen atom, halogen atom, or C 1-2 It is an alkoxy, R A12 teeth, It is a hydrogen atom or a halogen atom;

[0399] Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 C 4-5 It is Alkandil, Also, C 4-5 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded may be replaced by the -O- formula.

[0400] R 4 The base is represented by the following formula [VI]

[0401] [ka] And, Here, The carbon ring is phenyl, The phenyl contains a halogen atom, a C1 alkyl, and C 1-2 It is substituted with one group selected from the group consisting of alkoxys and C1 alkylcarbonyls, and further, Halogen atom, C1 alkyl, C3 cycloalkyl, C 1-2 The group may be substituted with one to three groups selected identically or differently from the group consisting of alkoxys and C1 alkylcarbonyls.

[0402] In this embodiment (H-2), a more preferred embodiment is as follows: In the above formula [I-7], X is a carboxyl; W is a structure represented by the following formulas [III-5], [III-6], [III-8] to [III-11], or [III-13].

[0403] [ka] and; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formula [V-12] or [V-14].

[0404] [ka] And, R 4 This is a base represented by the following formulas [VI-2], [VI-6], [VI-12], [VI-25], [VI-27], [VI-28], [VI-30], or [VI-31].

[0405] [ka] That is the case.

[0406] And in this embodiment (H-2), One particularly preferred embodiment is that the compound represented by the aforementioned formula [I-7] is This is the case if any of the following apply:

[0407] [ka]

[0408] [ka]

[0409] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0410] [ka]

[0411] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0412] [ka]

[0413] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0414] [ka]

[0415] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0416] [ka]

[0417] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0418] [ka]

[0419] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0420] [ka]

[0421] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0422] [ka]

[0423] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0424] [ka]

[0425] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0426] [ka]

[0427] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0428] [ka]

[0429] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0430] [ka]

[0431] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0432] [ka]

[0433] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0434] [ka]

[0435] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0436] [ka]

[0437] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0438] [ka]

[0439] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0440] [ka]

[0441] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0442] [ka]

[0443] Furthermore, in this embodiment (H-2), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0444] [ka]

[0445] Another preferred embodiment of the compound of the present invention is the following embodiment (H-3). Appearance (H-3):

[0446] In this embodiment (H-3), preferred embodiments are as follows: In the compound represented by the above formula [I-1], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I-1] is the same as the compound represented by formula [I-7] below.

[0447] [ka] And, Here, R 2This is a base represented by the following formula [IV-1] or [IV-2]

[0448] [ka] and; X, W, ring B 1 , R B11 , R B12 , L 1 , ring B 2 , R B21 , R B22 , L 2 , and R 4 As stated above.

[0449] In this embodiment (H-3), a more preferred embodiment is as follows: In the above formula [I-7], X is a carboxyl or tetrazolyl;

[0450] W is a structure represented by the following formula [III-1]

[0451] [ka] And,

[0452] Here, In the structure represented by formula [III-1], Ring A 1 teeth, C 3-4 It is a cycloalkane, R A11 teeth, Hydrogen atom, halogen atom, or C 1-2 It is an alkoxy, R A12 teeth, It is a hydrogen atom or a halogen atom;

[0453] Ring B 1 It is phenyl, R B11 and R B12They are identically hydrogen atoms, L 1 C 4-5 Alkanedil (the C 4-5 The alkanediyl may be substituted with two fluorine atoms. Also, C 4-5 R is one of the carbon atoms in alkanediyl. 2 The atom that is two or more atoms away from the nitrogen atom to which it is bonded may be replaced by the -O- formula. Ring B 2 It is a partially saturated 9-membered fused ring aryl, R B21 and R B22 They are identically hydrogen atoms, L 2 It is a C2 alkanediyl;

[0454] R 4 The base is represented by the following formula [VI]

[0455] [ka] And, Here, The carbon ring is phenyl, The phenyl contains a halogen atom, C 1-3 Alkyl, C 1-2 It is substituted with one group selected from the group consisting of alkoxys and C1 alkylcarbonyls, and further, Halogen atom, C 1-3 Alkyl (the C 1-3 The alkyl group may be substituted with one hydroxyl group. 1-2 The group may be substituted with 1 to 3 groups selected identically or differently from the group consisting of alkoxy and C1 alkylcarbonyl groups.

[0456] In this embodiment (H-3), a more preferred embodiment is as follows: In the above formula [I-7], A more preferable X is carboxyl or tetrazolyl; W is a structure represented by the following formulas [III-5], [III-6], [III-8] to [III-11], or [III-13].

[0457] [ka] and; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formulas [V-3], [V-12], or [V-14].

[0458] [ka] And, Here, n4 is an integer of 4, Ring B 2 It is dihydroindenyl, R B21 and R B22 They are identically hydrogen atoms, L 2 The structure is represented by the following formula [V-20].

[0459] [ka] And, Here, n5 is 2; R 4 The base is represented by the following formulas [VI-2], [VI-6], [VI-7], [VI-8], [VI-10], [VI-11], [VI-12], [VI-25], [VI-27], [VI-28], [VI-30], or [VI-31].

[0460] [ka] That is the case.

[0461] And in this embodiment (H-3), One particularly preferred embodiment is that the compound represented by the aforementioned formula [I-7] is This is the case if any of the following apply:

[0462] [ka]

[0463] [ka]

[0464] [ka]

[0465] [ka]

[0466] [ka]

[0467] [ka]

[0468] [ka]

[0469] [ka]

[0470] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0471] [ka]

[0472] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0473] [ka]

[0474] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0475] [ka]

[0476] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0477] [ka]

[0478] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0479] [ka]

[0480] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0481] [ka]

[0482] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0483] [ka]

[0484] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0485] [ka]

[0486] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0487] [ka]

[0488] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0489] [ka]

[0490] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0491] [ka]

[0492] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0493] [ka]

[0494] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0495] [ka]

[0496] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0497] [ka]

[0498] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0499] [ka]

[0500] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0501] [ka]

[0502] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0503] [ka]

[0504] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0505] [ka]

[0506] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0507] [ka]

[0508] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0509] [ka]

[0510] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0511] [ka]

[0512] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0513] [ka]

[0514] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0515] [ka]

[0516] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0517] [ka]

[0518] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0519] [ka]

[0520] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0521] [ka]

[0522] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0523] [ka]

[0524] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0525] [ka]

[0526] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0527] [ka]

[0528] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0529] [ka]

[0530] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0531] [ka]

[0532] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0533] [ka]

[0534] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0535] [ka]

[0536] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0537] [ka]

[0538] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0539] [ka]

[0540] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0541] [ka]

[0542] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0543] [ka]

[0544] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0545] [ka]

[0546] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0547] [ka]

[0548] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0549] [ka]

[0550] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0551] [ka]

[0552] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0553] [ka]

[0554] Furthermore, in this embodiment (H-3), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-7] is as follows:

[0555] [ka]

[0556] Another preferred embodiment of the compound of the present invention is the following embodiment (J). Type (J):

[0557] In this embodiment (J), preferred embodiments are as follows: In the compound represented by the above formula [I], or a pharmaceutically acceptable salt thereof, or a hydrate thereof, The compound represented by formula [I] is the compound represented by the following formula [I-8]

[0558] [ka] And, Here, R X C 1-4 It is alkyl; W, ring B 1 , R B11 , R B12 , L 1 , and R 4 As stated above.

[0559] In this embodiment (J), a more preferred embodiment is as follows: In the above equation [I-8], R X is a C1 alkyl, C2 alkyl, or C4 alkyl; W is a structure represented by the following formula [III-1]

[0560] [ka] And, Here, In the structure represented by formula [III-1], Ring A 1 C 3-4 It is a cycloalkane, R A11 is a hydrogen atom, a halogen atom, or a C2 alkoxy, R A12 is a hydrogen atom or a halogen atom; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 It is C5 alkanediyl, One of the carbon atoms in the C5 alkanediyl is R 2 Any atom that is two or more atoms away from the nitrogen atom to which it is bonded may be replaced by the -O- atom; R 4 The base is represented by the following formula [VI]

[0561] [ka] And, Here, The carbon atom of the ring is phenyl. The phenyl is substituted with three groups, identically or differently selected from the group consisting of C2 alkoxys and C1 alkylcarbonyls, and further, It may be substituted with a single halogen atom.

[0562] In this embodiment (J), a more preferred embodiment is as follows: In the above equation [I-8], R X These are methyl, ethyl, or tert-butyl; W has a structure represented by the following formulas [III-5], [III-10], or [III-13].

[0563] [ka] and; Ring B 1 It is phenyl, R B11 and R B12 They are identically hydrogen atoms, L 1 The structure is represented by the following formula [V-14].

[0564] [ka] and; R 4 This is a base represented by the following formula [VI-10] or [VI-11]

[0565] [ka] That is the case.

[0566] And in this embodiment (J), one particularly preferred embodiment is as follows: The compound represented by the above formula [I-8] is one of the following:

[0567] [ka]

[0568] [ka]

[0569] [ka]

[0570] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0571] [ka]

[0572] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0573] [ka]

[0574] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0575] [ka]

[0576] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0577] [ka]

[0578] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0579] [ka]

[0580] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0581] [ka]

[0582] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0583] [ka]

[0584] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0585] [ka]

[0586] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0587] [ka]

[0588] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0589] [ka]

[0590] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0591] [ka]

[0592] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0593] [ka]

[0594] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0595] [ka]

[0596] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0597] [ka]

[0598] Furthermore, in this embodiment (J), other particularly preferred embodiments are as follows: The compound represented by the aforementioned formula [I-8] is as follows:

[0599] [ka]

[0600] The compounds of the present invention are compounds having a urea structure as their basic framework, and may also be pharmaceutically acceptable salts thereof, or hydrates thereof.

[0601] Pharmaceutically acceptable salts include, for example, mineral salts such as hydrochloride, hydrobromide, hydroiodide, phosphate, sulfate, and nitrate; sulfonates such as methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, and trifluoromethanesulfonate; organic salts such as oxalate, tartrate, citrate, maleate, succinate, acetate, trifluoroacetate, benzoate, mandelate, ascorbate, lactate, gluconate, and malate; amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate, and aspartate; inorganic salts such as lithium salt, sodium salt, potassium salt, calcium salt, and magnesium salt, or ammonium salts; and salts with organic bases such as triethylamine salt, diisopropylamine salt, cyclohexylamine salt, and N-methyl-D-glucamine salt. Note that hydrated salts are included in the definition of salt.

[0602] The compounds of the present invention may have chiral centers, in which case various optical isomers exist. Therefore, the compounds of the present invention may exist as separate optically active (R) and (S) isomers, and as a racemic mixture or (RS) mixture. Furthermore, in the case of compounds having two or more chiral centers, diastereomers also exist depending on the optical isomerism. The compounds of the present invention also include mixtures containing all of these types in any proportion. For example, diastereomers can be separated by methods well known to those skilled in the art, such as fractional crystallization, and optically active isomers can be obtained by organic chemical methods well known for this purpose. In addition, the compounds of the present invention may have geometric isomers such as cis and trans isomers. Furthermore, the compounds of the present invention are tautomeristic, and various tautomers exist. The compounds of the present invention also include these isomers, and mixtures containing these isomers in any proportion. Furthermore, if the compound or salt thereof of the present invention forms a hydrate or solvate, these are also included within the scope of the present invention.

[0603] As mentioned earlier, LPA1 receptors, LPA3 receptors, and others perform a variety of functions in the body. Diseases caused by LPA receptors include, for example, diseases involving fibrosis (idiopathic pulmonary fibrosis, systemic sclerosis, chronic kidney disease, chronic hepatitis, chronic rejection after organ transplantation, etc.), inflammatory diseases (rheumatoid arthritis, osteoarthritis of the knee, etc.), cardiovascular diseases (arteriosclerosis, etc.), cancer-related diseases (prostate cancer, breast cancer, ovarian cancer, etc.), urinary tract diseases (benign prostatic hyperplasia, overactive bladder, etc.), and neurological diseases (neuropathic pain, diabetic neuropathy, etc.).

[0604] Drugs that inhibit the physiological activity of LPA receptors, particularly antagonists to the EDG family such as LPA1 and LPA3 receptors, are considered useful as preventive or therapeutic agents for diseases involving organ fibrosis such as idiopathic pulmonary fibrosis, systemic sclerosis, chronic kidney disease, and chronic hepatitis; cardiovascular diseases such as arteriosclerosis; proliferative disorders including various cancers; urinary tract diseases such as benign prostatic hyperplasia; or central and peripheral neurological diseases.

[0605] Furthermore, the antagonistic effect of the compounds of the present invention on LPA receptors can be evaluated according to known methods, such as those described in the test examples of this specification below.

[0606] With respect to the pharmaceutical product according to the present invention, the compounds of the present invention that antagonize the LPA1 receptor, or pharmaceutically acceptable salts thereof, or hydrates thereof, can be administered alone or together with pharmaceutically or pharmaceutically acceptable additives.

[0607] As additives, commonly used excipients or diluents may be used, and if necessary, commonly used binders, disintegrants, lubricants, coatings, sugar coatings, pH adjusters, solvents, or aqueous or non-aqueous solvents may be used. Specifically, examples include water, lactose, dextrose, fructose, sucrose, sorbitol, mannitol, polyethylene glycol, propylene glycol, starch, corn starch, gum, gelatin, alginate, calcium silicate, calcium phosphate, cellulose, water syrup, methylcellulose, polyvinylpyrrolidone, alkyl p-hydroxybenzoate, talc, stearic acid, magnesium stearate, agar, pectin, gum arabic, glycerin, sesame oil, olive oil, soybean oil, cocoa butter, ethylene glycol, low viscosity hydroxypropyl cellulose (HPC-L), microcrystalline cellulose, carboxymethylcellulose (CMC), sodium carboxymethylcellulose (CMC-Na), and other commonly used substances.

[0608] The pharmaceutical product according to the present invention may be in the form of a solid composition, a liquid composition, or any other composition, and the most suitable form may be selected as needed.

[0609] The pharmaceutical product according to the present invention can be prepared by adding the aforementioned additives to the compound of the present invention and using conventional pharmaceutical formulation techniques to create tablets, pills, capsules, granules, powders, liquids, emulsions, suspensions, injections, etc.

[0610] Furthermore, the pharmaceutical product according to the present invention can be formulated by forming an inclusion compound with the compound of the present invention and α, β, or γ-cyclodextrin or methylated cyclodextrin, etc.

[0611] The pharmaceutical product according to the present invention can be a single formulation (combination formulation) or two or more formulations (combination formulations) obtained by separately formulating compounds that can be used in combination with the compound of the present invention. When these compounds are formulated separately to produce two or more formulations, the individual formulations can be administered simultaneously or at regular intervals. In this case, the order in which they are administered does not matter. The two or more formulations can also be administered at different rates per day. Furthermore, the two or more formulations can be administered via different routes.

[0612] When these compounds are formulated separately to create two different formulations, they may be administered simultaneously or at very short intervals. For example, it is preferable to include information in the package insert or sales brochure of the commercially available drug stating that they should be used in combination. Furthermore, it is also preferable to formulate these active ingredients separately and create a kit consisting of two different formulations.

[0613] When using the compound of the present invention as an LPA1 receptor antagonist or the like, the compound may be administered orally as is. Alternatively, the compound may be administered orally as a preparation containing the compound of the present invention as an active ingredient.

[0614] When the compound of the present invention is used as a preventive or therapeutic agent for systemic sclerosis, the compound may be administered orally as is. Alternatively, the compound may be administered orally as a preparation containing the compound of the present invention as an active ingredient.

[0615] The dosage of the compound of the present invention varies depending on the target patient, route of administration, target disease, symptoms, etc., but for example, when administered orally to an adult patient, the usual single dose is 0.1 mg to 1000 mg, preferably 1 mg to 200 mg, and it is desirable to administer this amount once to three times a day, or once every two to three days.

[0616] The following describes in detail a method for producing compound [I] according to the present invention, but the production method is not particularly limited to those exemplified. Furthermore, in the production of compound [I] of the present invention, the order of each step in each production method can be changed as appropriate.

[0617] Furthermore, the solvent used in the reaction can be any solvent that does not inhibit each reaction, and is not limited to the following description.

[0618] Furthermore, in each of the following manufacturing methods, the raw material compound may be used as a salt. Alternatively, the target compound may be manufactured as a salt. Examples of salts that can be used here include the aforementioned "pharmaceutically acceptable salts."

[0619] Compound [Ia] according to the present invention can be produced by a method for producing compound [I] or a method similar thereto.

[0620] Compound [I] of the present invention can be produced by methods known to the present day, for example, by the following production methods 1 to 6 or similar methods.

[0621] In detail, among the compounds [I] of the present invention, X is carboxyl or C 1-4 Method 1 shows how to produce a compound that is an alkoxycarbonyl, and Methods 2 to 8 show how to produce the intermediate for that compound. Furthermore, the manufacturing methods for compounds in which X is tetrazolyl, compounds with a group represented by the following formula [II-1] (hereinafter sometimes referred to as compound [II-1]), compounds in which X is carbamoyl, compounds with a group represented by the following formulas [II-2], [II-3], or [II-4] (hereinafter sometimes referred to as compound [II-2], compound [II-3], and compound [II-4], respectively), and compounds with a group represented by the following formula [II-5] (hereinafter sometimes referred to as compound [II-5]) are shown in Manufacturing Method 9.

[0622] [ka]

[0623] In this general manufacturing method, "reductive amination reaction" refers to a reaction in which, for example, in an inert solvent or under solvent-free conditions, at temperatures ranging from ice-cold to reflux, in or without the presence of an acid such as formic acid or acetic acid, a corresponding imine compound is formed from an aldehyde or ketone compound and an amine compound, and then a reducing agent such as sodium triacetoxyborohydride, sodium cyanoborohydride, sodium borohydride, 2-picolinborane, or iridium catalyst such as chloro(pentamethylcyclopentadienyl)(8-quinolinolate)iridium(III) (for example, as described in Advanced Synthesis and Catalysis, Vol. 360, p. 322, 2018) is reacted to produce an amine compound.

[0624] Furthermore, in this general manufacturing method, "condensation reaction" refers to a reaction in which a carboxylic acid compound and an amine compound are reacted with a condensing agent in an inert solvent, at room temperature to reflux temperature, in or without the presence of a base and an additive, to produce an amide compound.

[0625] Examples of condensing agents used in the "condensation reaction" include O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU), O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC), 1,1'-carbonyldiimidazole (CDI), (1H-benzotriazol-1-yloxy)(tripyrrolidine-1-yl)phosphonium hexafluorophosphate (PyBOP), anhydrous propylphosphonic acid (T3P), and 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholinium chloride (DMT-MM).

[0626] Examples of additives used in the "condensation reaction" include N-hydroxybenzotriazole monohydrate (HOBt) and N-hydroxysuccinimide.

[0627] Examples of bases used in the "condensation reaction" include tertiary aliphatic amines such as N,N-diisopropylethylamine and triethylamine, and pyridines.

[0628] Furthermore, in this general manufacturing method, "hydrolysis reaction" refers to a reaction in which, for example, a base such as lithium hydroxide, sodium hydroxide, or potassium hydroxide is used in an inert solvent at a temperature ranging from ice-cold to reflux to produce carboxylic acid compounds and alcohol compounds from ester compounds.

[0629] Of the compounds [I] of the present invention, X is carboxyl, and R 1 Compounds in which the atom is a hydrogen atom [1-d] and R 1 Compounds [1-f] in which the compound is methyl can be produced, for example, by the following production method 1 or a similar method. Manufacturing method 1: Scheme 1 (Method for producing compounds [1-d] and [1-f] from compound [1-a]):

[0630] [ka] [In the scheme, R 2 , R 3 , R 4 , and W are the same as defined above, Alk 1 C 1-4 [Indicates alkyl.]

[0631] Process 1-1: Method for producing compound [1-c]: Compound [1-c] can be produced by reacting compound [1-b] with compound [1-a] as a starting material in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a base such as triethylamine, pyridine, 4-dimethylaminopyridine, and N,N-diisopropylethylamine, and a urea-forming agent such as 4-nitrophenyl chloroformate, CDI, or triphosgene. Step 1-2: Method for producing compound [1-d]: Compound [1-d] can be produced by using compound [1-c] as a starting material and carrying out a "hydrolysis reaction". Step 1-3: Method for producing compound [1-e]: Compound [1-e] can be produced by using compound [1-c] as a starting material and reacting it with a methylating agent such as methyl iodide in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a base such as sodium hydride. Step 1-4: Method for producing compound [1-f]: Compound [1-f] can be produced by using compound [1-e] as a starting material and carrying out a "hydrolysis reaction" by the method described in step 1-2 above or a similar method.

[0632] The compounds [1-d] and [1-f] obtained in this manner can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0633] Furthermore, among the compounds [I] of the present invention, X is C 1-4 The alkoxycarbonyl compound can be produced, for example, as compound [1-c] or [1-e] by the present manufacturing method 1 or a similar method.

[0634] Now, among the intermediates for the production of compound [I] of the present invention, compounds [1-a] and [1-b] described in Scheme 1 can be obtained by manufacturing by methods known to the present invention or by purchasing commercially available products. Furthermore, compound [1-a] can also be produced, for example, by manufacturing method 2 described below or a similar method. Similarly, compound [1-b] can also be produced, for example, by the production method 8 described below or a similar method.

[0635] An example of the production of compound [1-a], which is a production intermediate for compound [I] of the present invention, is shown in scheme 2-1 of production method 2 below. Manufacturing method 2: Scheme 2-1 (Method for producing compound [1-a] from compound [2-a]):

[0636] [ka] [In the scheme, R 2 , R 3 , R 4 , n12, n13, n22, n23, ring B 1 , R B11 , R B12 , ring B 2 , R B21 , and R B22 This is the same as the definition above; Ring B 1 As mentioned above, C 3-8 This represents a cycloalkyl, a 4-8 member saturated heterocyclyl containing a nitrogen atom, a phenyl, or a 5-6 member heteroaryl containing a nitrogen atom. Ring B 2 Also, as described above, it represents a partially saturated 9-10 membered fused aryl ring, or a 9-10 membered fused heteroaryl ring containing a nitrogen atom. LG 1 This indicates a leaving group, Here, LG 1 The "leaving group" represented by this symbol is, for example, a halogen atom such as a chlorine atom or a bromine atom; or a C atom such as methanesulfonyloxy. 1-4 Alkyl sulfonyloxy; or aryl sulfonyloxy such as p-toluenesulfonyloxy; R 2 ' is C 5-9 Alkyl, C 5-9 Alkenil, C 5-9 This refers to an alkynyl group, or a group represented by the following formula [IV-1'] or [IV-2'],

[0637] [ka] Here, Ring B 1 , ring B 2 , R B11 , R B12 , RB21 , and R B22 This is the same as the definition above, L 1 ' is C 2-7 Alkanedil (the C 2-7 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) Or it may have a structure represented by the following formula [V-1'],

[0638] [ka] Here, n12 and n13 are the same as defined above. n11' represents an integer between 1 and 2. Also, L 1 ' is C 2-7 Alkanedil (the C 2-7 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) When the C 2-7 R is one of the carbon atoms in alkanediyl. 2’ The carbon atom that is one or more atoms away from the carboxyl or formyl to which it is bonded is of the formula -O-, -S-, or -N(R L11 )- can be replaced with, Here, R L11 This is the same as the definition above, Also, L 1 ' is C 2-7 Alkanedil (the C 2-7 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) When the C 2-7 Two consecutive carbon atoms in an alkanediyl are in the formula -C(=O)N(R L12 )- can be replaced with, Here, R L12 This is the same as the definition above, L 2 ' is C 2-7 Alkanedil (the C 2-7The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) Or it may have a structure represented by the following formula [V-2'],

[0639] [ka] Here, n22 and n23 are the same as defined above. n21' represents an integer between 1 and 2. Also, L 2 ' is C 2-7 Alkanedil (the C 2-7 The alkanediyl may be substituted with 1 to 5 fluorine atoms. ) When the C 2-7 R is one of the carbon atoms in alkanediyl. 2’ The carbon atom that is one or more atoms away from the carboxyl or formyl to which it is bonded is of the formula -O-, -S-, or -N(R L21 )- can be replaced with, Here, R L21 As mentioned above, hydrogen atoms or C 1-3 It indicates alkyl, Also, C 2-7 Two consecutive carbon atoms in an alkanediyl are in the formula -C(=O)N(R L22 )- can be replaced with, Here, R L22 As mentioned above, hydrogen atoms or C 1-3 [Indicates alkyl.]

[0640] Process 2-1: Method for producing compound [1-a]: Compound [1-a] can be produced by reacting compound [2-a] as a starting material with compound [2-b] in an inert solvent at room temperature to reflux temperature in the presence of a base. Examples of bases used in this reaction include amine compounds such as triethylamine, N,N-diisopropylethylamine, and 1,8-diazabicyclo[4,3,0]undeca-7-ene; alkali metal hydrides such as sodium hydride; alkali metal hydroxides such as potassium hydroxide; alkali metal carbonates such as cesium carbonate, potassium carbonate, and sodium carbonate; and alkoxyalkali metals such as tert-butoxy potassium. Process 2-2: Alternatively, compound [1-a] can be produced by carrying out a "reductive amination reaction" with compound [2-a] and compound [2-c], [2-c'], or [2-c'']. Step 2-3: Method for producing compound [2-e]: Compound [2-e] can also be produced by a "condensation reaction" between compound [2-a] and compound [2-d]. Step 2-4: Alternatively, a method for producing compound [1-a]: Compound [1-a] can be produced by using compound [2-e] as a starting material and reacting it with a reducing agent such as a borane-tetrahydrofuran complex or a borane-dimethyl sulfide complex in an inert solvent at a temperature ranging from ice-cold to reflux.

[0641] Furthermore, compound [1-a] can also be produced, for example, by the manufacturing method shown in scheme 2-2 below or a similar method. Scheme 2-2 (Method for producing compound [1-a] from compound [2-f]):

[0642] [ka] [In the scheme, R 2 , R 3 , and R 4 This is the same as the definition above.

[0643] Step 2-5: Alternative method for producing compound [1-a]: Compound [1-a] can be produced by performing a "reductive amination reaction" between compound [2-f] and compound [2-g].

[0644] Furthermore, in compound [1-a], R 3 C 1-3 The alkyl compound [1-a'] can also be produced, for example, by the manufacturing method shown in Scheme 2-3 below or a similar method. Scheme 2-3 (Method for producing compound [1-a'] from compound [2-h]):

[0645] [ka] [In the scheme, R 2 and R 4 This is the same as the definition above, R 3 ' is C 1-3 [Indicates alkyl.] Step 2-6: Method for producing compound [2-j]: Compound [2-j] can be produced by reacting compound [2-g] with compound [2-h] as a starting material, in the presence or absence of an acid such as formic acid or acetic acid, in an inert solvent or under solvent-free conditions, at a temperature ranging from ice-cold to reflux. Step 2-7: Method for producing compound [1-a']: Compound [1-a'] can be produced by reacting compound [2-k] with compound [2-j] as a starting material in an inert solvent at a temperature ranging from ice-cold to room temperature. Furthermore, steps 2-6 and 2-7 can be carried out consecutively without removing compound [2-j], which is the imine produced in step 2-6 (without post-processing the reaction in step 2-6).

[0646] The compounds [1-a] and [1-a'] obtained in this manner can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0647] Furthermore, by reacting compound [2-j] obtained in step 2-6 with a reducing agent used in the "reductive amination reaction", compound [1-a] is subjected to R 3 It is also possible to produce compounds in which the atom is a hydrogen atom.

[0648] Now, among the intermediates for the production of compound [I] of the present invention, compounds [2-a], [2-b], [2-c], [2-c'], [2-c''], and [2-d] described in scheme 2-1, compounds [2-f] and [2-g] described in scheme 2-2, and compounds [2-g], [2-h], and [2-k] described in scheme 2-3 can be obtained by manufacturing by methods known to the present invention or by purchasing commercially available products. Furthermore, among these compounds, the compound [2-a] whose structure is represented by [2-a'] described later (hereinafter sometimes referred to as compound [2-a']) can be produced, for example, by manufacturing method 3 described later or a similar method, and the compound [2-f] whose structure is represented by [2-f'] described later (hereinafter sometimes referred to as compound [2-f']), and [2-h] can be produced, for example, by manufacturing method 6 described later or a similar method.

[0649] [ka] Similarly, compounds [2-b], [2-c], compound [2-d] whose structure is represented by [5-e] described later (hereinafter sometimes referred to as compound [5-e]), compound [2-d] whose structure is represented by [5-e'] described later (hereinafter sometimes referred to as compound [5-e']), and [2-g] can also be produced, for example, by manufacturing methods 4, 5, or 7 described later or by methods equivalent thereto.

[0650] [ka]

[0651] An example of the production of compound [2-a'], which is a production intermediate for compound [I] of the present invention, is shown in scheme 3-1 of production method 3 below. Manufacturing method 3: Scheme 3-1 (Method for producing compound [2-a'] from compound [2-h]):

[0652] [ka] [In the scheme, R 3 'and R 4 This is the same as the definition above, M is a lithium atom or the formula -MgX M Show, X M This represents a chlorine atom, a bromine atom, or an iodine atom. Compound [2-k'](R 3 '-M) indicates an alkyl metal reagent, Alk 2 This indicates tert-butyl, etc.

[0653] Step 3-1: Method for producing compound [3-b]: Compound [3-b] can be produced by reacting compound [2-h] as a starting material with compound [3-a] in an inert solvent at room temperature to 160°C in the presence of a Lewis acid such as tetraethyl orthotitanate. Step 3-2: Method for producing compound [3-c]: Compound [3-c] can be produced by reacting compound [3-b] as a starting material with compound [2-k'] in an inert solvent at -20°C to room temperature. Step 3-3: Method for producing compound [2-a']: Compound [2-a'] can be produced by using compound [3-c] as a starting material and reacting it with an acid such as hydrochloric acid in an inert solvent at a temperature ranging from ice-cold to room temperature. Furthermore, steps 3-1, 3-2, and 3-3 can be carried out with reference to the methods described in, for example, Journal of Combinatorial Chemistry, Vol. 5, p. 590, 2003; Organic Letters, Vol. 3, p. 3707, 2001. Furthermore, in this scheme 3-1, compound [2-a'] can be stereoselectively produced by reacting the optically active compound [3-a] in step 3-1.

[0654] Now, in compound [2-a], R 4 A phenyl in which C is substituted, wherein C is located at the para position of the phenyl. 1-6 Compounds substituted with alkylcarbonyl [3-e], and hydroxylated C 1-6 The alkyl-substituted compounds [3-f] can also be produced, for example, by the method described in Scheme 3-2 below or a similar method. Scheme 3-2 (Method for producing compounds [3-e] and [3-f] from compound [3-c']):

[0655] [ka] [In the scheme, R 3 and Alk 2 This is the same as the definition above, Alk 3 and Alk 4 Each of them is independent of C 1-6 Alkyl, Halo C 1-6 Alkyl, C 3-8 It shows cycloalkyl, R α1 C 1-6 Alkyl (the C 1-6 The alkyl group may be substituted with one hydroxyl group. 1-6 Alkyl, C 3-8 Cycloalkyl, C 1-6 Alkylcarbonyl and Halo C 1-6 It shows an alkylcarbonyl, Alk 5 C 1-6 C substituted with alkyl or hydroxyl 1-6 It indicates alkyl, LG 2 This indicates a leaving group. Here, LG 2 The "leaving group" represented by this symbol refers to, for example, a halogen atom such as a chlorine atom, a bromine atom, or an iodine atom.

[0656] Step 3-4: Method for producing compound [3-d]: Compound [3-d] can be produced by reacting compound [3-c'] as a starting material with a palladium catalyst such as palladium(II) acetate, a phosphine ligand such as 1,3-bis(diphenylphosphine)propane or 2,2'-bis(diphenylphosphine)-1,1'-binaphthyl, and a vinyl ether such as ethylene glycol monovinyl ether or butyl vinyl ether in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a base such as potassium carbonate or triethylamine. This process can be carried out by referring to, for example, the methods described in The Journal of Organic Chemistry, Vol. 66, p. 4340, 2001; and The Journal of Organic Chemistry, Vol. 72, p. 6390, 2007. Step 3-5: Method for producing compound [3-e]: Compound [3-e] can be produced by using compound [3-d] as a starting material and reacting it with an acid such as hydrochloric acid in an inert solvent at a temperature ranging from ice-cold to room temperature. Steps 3-4 and 3-5 can be carried out consecutively as a one-pot reaction. Alternatively, this step may be performed in a later step. Step 3-6: Method for producing compound [3-f]: Compound [3-f] can be produced by using compound [3-e] as a starting material and reacting it with a reducing agent such as lithium aluminum hydride (LiAlH4) or lithium borohydride (LiBH4) in an inert solvent at -78°C to room temperature.

[0657] The compounds [2-a'], [3-e], and [3-f] obtained in this manner can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0658] Now, among the intermediates for the production of compound [I] of the present invention, compounds [2-h] and [3-a] described in scheme 3-1, and compound [3-c'] described in scheme 3-2, can be obtained by manufacturing by methods known to the present invention or by purchasing commercially available products. Furthermore, among these compounds, compound [3-c'] can also be produced, for example, by the method described in step 3-2 above or a similar method.

[0659] Of the intermediates used to produce compound [I] of the present invention, compound [2-b] described in manufacturing method 2 can also be produced, for example, by manufacturing method 4 or a similar method.

[0660] [ka]

[0661] An example of the production of compound [2-b], which is a production intermediate for compound [I] of the present invention, is shown in the following scheme 4-1. Manufacturing method 4: Scheme 4-1: Method for producing compound [2-b] from compound [4-a]

[0662] [ka] [In the scheme, R 2 and LG 1 This is the same as the definition above.

[0663] Step 4-1: Method for producing compound [2-b]: Starting with compound [4-a], (i) in an inert solvent, at ice-cold to room temperature, in the presence or absence of a base such as triethylamine, in the presence or absence of an additive such as trimethylamine hydrochloride, an aryl sulfonyl chloride such as p-toluenesulfonyl chloride, or a C such as methanesulfonyl chloride. 1-4 Compound [2-b] can be produced by reacting with alkyl sulfonyl chloride, or (ii) reacting with a brominating agent such as lithium bromide in an inert solvent at room temperature to reflux temperature. This process can be carried out by referring, for example, to the method described in Tetrahedron, Vol. 55, p. 2183, 1999. The compound [4-a] used as a raw material in step 4-1 above can be obtained by manufacturing by a method known to the public or by purchasing a commercially available product. Furthermore, among the compounds [4-a], the compound whose structure is represented by formula [5-b] described later (hereinafter sometimes referred to as compound [5-b]) can be produced, for example, by the method described in scheme 5-1 of production method 5 described later or by a similar method.

[0664] [ka]

[0665] Furthermore, in compound [2-b], R 2 The group is represented by the aforementioned formula [IV-1], and L 1 Compounds [4-m], which are C4 alkanediyl compounds in which one fluorine atom is substituted, and L 1 Compound [4-h], which is a C4 alkanediyl substituted with two fluorine atoms, can also be produced, for example, by the production method described in scheme 4-5 below or a similar method.

[0666] [ka]

[0667] Examples of the preparation of the aforementioned compounds [4-m] and [4-h] are shown in Scheme 4-2. Here, compound [4-m], which is substituted with one fluorine atom, can be produced by starting compound [4-b] and fluorinating the corresponding hydroxy compound [4-d] to produce compound [4-j], and compound [4-h], which is substituted with two fluorine atoms, can be produced by fluorinating the corresponding ketone compound [4-e] to produce compound [4-f]. Furthermore, in functional group transformations, protection and deprotection of hydroxyl groups, etc., can be carried out as appropriate. Scheme 4-2 (Method for producing compound [4-h] or compound [4-m] from compound [4-b]):

[0668] [ka] [In the scheme, Ring B 1 LG 1 , R B11 and R B12 This is the same as the definition above, PG 1 This shows a hydroxyl protecting group such as acetyl, LG 3 This indicates a leaving group. Here, LG 3 The "leaving group" represented by C is, for example, C 1-6 [This indicates an alkoxy.]

[0669] Step 4-2: Method for producing compound [4-c]: Compound [4-c] can be produced by using compound [4-b] as a starting material and reacting it with a reducing agent in an inert solvent at a temperature ranging from ice-cold to room temperature. As a reducing agent, LG 3 C 1-6 When it is an alkoxy, for example, lithium aluminum hydride or lithium borohydride can be used. Step 4-3: Method for producing compound [4-d]: Compound [4-d] can be produced by using compound [4-c] as a starting material and reacting it with acetic anhydride or the like in an inert solvent at ice-cold to room temperature in the presence of a base such as N,N-diisopropylethylamine, thereby selectively protecting the primary hydroxyl group. Step 4-4: Method for producing compound [4-e]: Compound [4-e] can be produced by using compound [4-d] as a starting material and reacting it with an oxidizing agent such as manganese dioxide or des-martin periodinane in an inert solvent at a temperature ranging from ice-cold to room temperature. Step 4-5: Method for producing compound [4-f]: Compound [4-f] can be produced by using compound [4-e] as a starting material and reacting it with a fluorinating agent such as bis(2-methoxyethyl)aminosulfate trifluoride or (diethylamino)sulfate trifluoride in an inert solvent or under solvent-free conditions at a temperature from ice-cold to 50°C. Step 4-6: Method for producing compound [4-g]: Compound [4-g] can be produced by using compound [4-f] as a starting material and reacting it with a basic aqueous solution such as sodium hydroxide aqueous solution in an inert solvent at a temperature ranging from ice-cold to room temperature to deprotect the hydroxyl protecting group. Step 4-7: Method for producing compound [4-h]: Compound [4-h] can be produced using compound [4-g] as a starting material by the method described in step 4-1 above or a similar method. Step 4-8: Method for producing compound [4-j]: Compound [4-j] can be produced using compound [4-d] as a starting material by the method described in steps 4-5 above or a similar method. Step 4-9: Method for producing compound [4-k]: Compound [4-k] can be produced using compound [4-j] as a starting material by the method described in steps 4-6 above or a similar method. Step 4-10: Method for producing compound [4-m]: Compound [4-m] can be produced using compound [4-k] as a starting material by the method described in step 4-7 above or by a similar method.

[0670] In Scheme 4-2, by using compound [4-b'] instead of compound [4-b] as the starting material, R 2 The group is represented by the aforementioned formula [IV-2], and L 2 Compounds [4-m'], which are C4 alkanediyl compounds in which one fluorine atom is substituted, and L 2 Compound [4-h'], a C4 alkanediyl in which two fluorine atoms are substituted, can be produced by the same method as described above for compounds [4-h] and [4-m]. Compound [4-b'] can be produced by known methods or obtained by purchasing a commercially available product.

[0671] [ka] [In the formula, Ring B 2 , R B21 , R B22 LG 1 , and LG 3 This is the same as the definition above.

[0672] Furthermore, in compound [2-b], R 2 The group is represented by the aforementioned formula [IV-1], and L 1 Compounds [4-x], which are C4 alkanediyl compounds substituted with one fluorine atom, and L 1 Compound [4-u], which is a C4 alkanediyl in which two fluorine atoms are substituted, can also be produced, for example, by the production method described in scheme 4-3 below or by a similar method.

[0673] [ka]

[0674] Examples of the preparation of the aforementioned compounds [4-x] and [4-u] are shown in Scheme 4-3. Here, compound [4-x], which is substituted with one fluorine atom, can be produced by starting compound [4-n] and fluorinating the corresponding hydroxy compound [4-q] to produce compound [4-v], while compound [4-u], which is substituted with two fluorine atoms, can be produced by fluorinating the corresponding ketone compound [4-r] to produce compound [4-s]. Furthermore, in functional group transformations, protection and deprotection of hydroxyl groups, etc., can be carried out as appropriate. Scheme 4-3 (Method for producing compound [4-u] or compound [4-x] from compound [4-n]):

[0675] [ka] [In the scheme, Ring B 1 , R B11 , R B12 PG 1 LG 1 , and LG 3 This is the same as the definition above.

[0676] Step 4-11: Method for producing compound [4-p]: Compound [4-p] can be produced using compound [4-n] as a starting material by the method described in step 4-2 above or by a similar method. Step 4-12: Method for producing compound [4-q]: Compound [4-q] can be produced using compound [4-p] as a starting material by the method described in step 4-3 above or a similar method. Step 4-13: Method for producing compound [4-r]: Compound [4-r] can be produced using compound [4-q] as a starting material by the method described in step 4-4 above or by a similar method. Step 4-14: Method for producing compound [4-s]: Compound [4-s] can be produced using compound [4-r] as a starting material by the method described in steps 4-5 above or a similar method. Step 4-15: Method for producing compound [4-t]: Compound [4-t] can be produced using compound [4-s] as a starting material by the method described in step 4-6 above or by a similar method. Step 4-16: Method for producing compound [4-u]: Compound [4-u] can be produced using compound [4-t] as a starting material by the method described in step 4-7 above or by a similar method. Step 4-17: Method for producing compound [4-v]: Compound [4-v] can be produced using compound [4-q] as a starting material by the method described in step 4-8 above or a similar method. Step 4-18: Method for producing compound [4-w]: Compound [4-w] can be produced using compound [4-v] as a starting material by the method described in step 4-9 above or by a similar method. Step 4-19: Method for producing compound [4-x]: Compound [4-x] can be produced using compound [4-w] as a starting material by the method described in step 4-10 above or a similar method.

[0677] In scheme 4-3, by using compound [4-n'] instead of compound [4-n] as the starting material, R 2 The group is represented by the aforementioned formula [IV-2], and L 2 Compound [4-x'] is a C4 alkanediyl substituted with one fluorine atom, and L 2 Compound [4-u'], a C4 alkanediyl in which two fluorine atoms are substituted, can be produced by the same method as described above for compounds [4-x] and [4-u]. Compound [4-n'] can be obtained by production by known methods or by purchasing a commercially available product.

[0678] [ka] [In the formula, Ring B 2 , R B21 , R B22 LG 1 , and LG 3 This is the same as the definition above.

[0679] The compounds obtained in this way, [2-b], [4-h], [4-h'], [4-m], [4-m'], [4-u], [4-u'], [4-x], and [4-x'], can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0680] Among the intermediates used in the production of compound [I] of the present invention, compound [4-a] described in scheme 4-1, compound [4-b] described in scheme 4-2, and compound [4-n] described in scheme 4-3 can be obtained by manufacturing by methods known to the public or by purchasing commercially available products.

[0681] Of the intermediates used to produce compound [I] of the present invention, compounds [2-c] and [5-e] described in manufacturing method 2 can also be produced, for example, by manufacturing method 5 or a similar method.

[0682] [ka] Manufacturing method 5:

[0683] An example of the production of compound [2-c], which is a production intermediate for compound [I] of the present invention, is shown in the following scheme 5-1. Scheme 5-1 (Method for producing compound [2-c] from compound [2-d]):

[0684] [ka] [In the scheme, R 2' is the same as the definition above, LG 4 This indicates a leaving group. Here, LG 4 The "leaving group" represented by C is, for example, C 1-6 [This indicates an alkoxy.]

[0685] Step 5-1: Method for producing compound [5-a]: Compound [5-a] can be produced by using compound [2-d] as a starting material and reacting it with an acid such as sulfuric acid in an alcohol solvent such as methanol or ethanol at a temperature ranging from ice-cold to reflux. Step 5-2: Method for producing compound [5-b]: Compound [5-b] can be produced using compound [5-a] as a starting material by the method described in step 4-2 above or by a similar method. Step 5-3: Alternative method for producing compound [5-b]: Compound [5-b] can be produced by using compound [2-d] as a starting material and reacting it with a reducing agent such as a borane-tetrahydrofuran complex in an inert solvent at a temperature ranging from ice-cold to room temperature. Step 5-4: Method for producing compound [2-c]: Compound [2-c] can be produced using compound [5-b] as a starting material by the method described in step 4-4 above or by a similar method. The compound [2-d] used as a raw material in steps 5-1 and 5-3 above can be obtained by manufacturing by known methods or by purchasing a commercially available product.

[0686] An example of the preparation of compound [5-e] is shown in the following scheme 5-2. Scheme 5-2 (Method for producing compound [5-e] from compound [5-c]):

[0687] [ka] [In the scheme, Ring B 1 , R B11 , and RB12 This is the same as the definition above, LG 5 This indicates a leaving group, Here, LG 5 The "leaving group" represented by this symbol is, for example, a halogen atom such as a chlorine atom or a bromine atom; or a C atom such as methanesulfonyloxy. 1-4 Alkyl sulfonyloxy; or aryl sulfonyloxy such as p-toluenesulfonyloxy, Y 1 This is formula -O-, formula -S-, or formula -N(R L11 )- indicates, Here, R L11 This is the same as the definition above, L X11 C 1-5 Showing alkanedils, L X12 C may be substituted with a single bond or 1 to 5 fluorine atoms. 1-5 [Indicates alkanedyls.]

[0688] Step 5-5: Method for producing compound [5-e]: Compound [5-e] can be produced by reacting compound [5-d] with compound [5-c] as a starting material in an inert solvent such as tetrahydrofuran or N-methylpyrrolidone at a temperature ranging from ice-cold to reflux, in the presence of a base such as sodium hydride.

[0689] In Scheme 5-2, compound [5-e'] can be produced in the same manner as the aforementioned manufacturing method for compound [5-e] by using compound [5-c'] instead of compound [5-c] and compound [5-d'] instead of compound [5-d] as starting materials. Compounds [5-c'] and [5-d'] can be obtained by manufacturing by known methods or by purchasing commercially available products.

[0690] [ka] [In the formula, Ring B 2 , R B21 , R B22, and LG 5 This is the same as the definition above, Y 2 This is formula -O-, formula -S-, or formula -N(R L21 )- indicates, Here, R L21 This is the same as the definition above, L X21 C 1-5 Showing alkanedils, L X22 C may be substituted with a single bond or 1 to 5 fluorine atoms. 1-5 [Indicates alkanedyls.]

[0691] The compounds [2-c], [5-e], and [5-e'] obtained in this manner can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0692] Of the intermediates used in the production of compound [I] of the present invention, compound [2-d] described in scheme 5-1 and compounds [5-c] and [5-d] described in scheme 5-2 can be obtained by manufacturing by methods known to the present invention or by purchasing commercially available products.

[0693] Of the intermediates used in the production of compound [I] of the present invention, compound [2-f'] described in production method 2 can also be produced, for example, by production method 6 or a similar method.

[0694] [ka] Manufacturing method 6:

[0695] An example of the production of compound [2-f'], which is a production intermediate for compound [I] of the present invention, is shown in the following scheme 6-1. Scheme 6-1 (Method for producing compound [2-f'] from compound [6-a]):

[0696] [ka] [In the scheme, R 3 ', R 4 , and M are the same as defined above, LG 6 This indicates a leaving group. Here, LG 6 The "leaving group" represented by this formula is, for example, the group represented by the formula -N(CH3)OCH3.

[0697] Step 6-1: Method for producing compound [2-f']: Compound [2-f'] can be produced by reacting compound [6-a] as a starting material with alkyllithium [2-k] in an inert solvent at -78°C to room temperature. This process can be carried out by referring, for example, to the method described in Synlett, Vol. 26, p. 1395, 2015. Step 6-2: Method for producing compound [6-a']: Compound [6-a'] can be produced by carrying out a "condensation reaction" between compound [6-a] and an amine compound such as N,O-dimethylhydroxylamine hydrochloride. Step 6-3: Alternative method for producing compound [2-f']: Compound [2-f'] can be produced by reacting compound [6-a'] as a starting material with compound [2-k'] in an inert solvent at a temperature ranging from ice-cold to room temperature. Scheme 6-2 (Method for producing compound [2-h] from compound [6-b]):

[0698] [ka] [In the scheme, R 4 This is the same as the definition above, LG 7 This indicates a leaving group. Here, LG 7 The "leaving group" represented by this symbol is, for example, hydroxy, C 1-6 [This indicates an alkoxy.]

[0699] Step 6-4: Method for producing compound [6-c]: Compound [6-c] can be produced by using compound [6-b] as a starting material and reacting it with a reducing agent in an inert solvent at a temperature ranging from ice-cold to room temperature. As a reducing agent, (i)LG 7 When is hydroxyl, for example, as in step 5-3 above, a borane-tetrahydrofuran complex can be used; (ii)LG 7 C 1-6 When it is an alkoxy, for example, lithium aluminum hydride or lithium borohydride can be used, as in step 4-2 described above. Step 6-5: Method for producing compound [2-h]: Compound [2-h] can be produced using compound [6-c] as a starting material by the method described in step 4-4 above or by a similar method.

[0700] Now, in compound [2-h], R 4 A compound [6-g] in which a phenyl atom is substituted, wherein a chlorine atom is substituted at the ortho position of the phenyl atom, can also be produced, for example, by the method described in Scheme 6-3 below or by a similar method. Scheme 6-3 (Method for producing compound [6-g] from compound [6-d]):

[0701] [ka] [In the scheme, Alk 3 and Alk 4 This is the same as the definition above, Alk 6 C 1-6 It indicates alkyl, R α2 C 1-6 Alkyl (the C 1-6 The alkyl group may be substituted with one hydroxyl group. 1-6 Alkyl, C 3-8 Cycloalkyl, C1-6 Alkylcarbonyl and Halo C 1-6 [Indicates an alkylcarbonyl group.]

[0702] Step 6-6: Method for producing compound [6-e]: Compound [6-e] can be produced by using compound [6-d] as a starting material and reacting it with a chloroforming agent such as sulfuryl chloride or N-chlorosuccinimide (NCS) in an inert solvent at a temperature of -60°C to 100°C. This chlorination reaction can also be carried out in a separate step.

[0703] Furthermore, in this process, by using 2 equivalents of a chlorinating agent relative to compound [6-d], the following compound [6-e'] can be produced, in which chlorine atoms are substituted at both ortho positions.

[0704] [ka] Step 6-7: Method for producing compound [6-f]: Compound [6-f] can be produced using compound [6-e] as a starting material by the method described in step 4-2 above or by a similar method. Step 6-8: Method for producing compound [6-g]: Compound [6-g] can be produced using compound [6-f] as a starting material by the method described in step 4-4 above or by a similar method.

[0705] Furthermore, in compound [2-h], R 4 A compound [6-m] in which a phenyl molecule is substituted, wherein a methyl molecule is substituted at the ortho position of the phenyl molecule, can also be produced, for example, by the method described in Scheme 6-4 below or by a similar method. Scheme 6-4 (Method for producing compound [6-m] from compound [6-d]):

[0706] [ka] [In the scheme, Alk 3 Alk 4 Alk 6 , and R α2 This is the same as the definition above.

[0707] Step 6-9: Method for producing compound [6-h]: Compound [6-h] can be produced by using compound [6-d] as a starting material and reacting it with an iodizing agent such as iodine in the presence of a silver compound such as silver trifluoroacetate in an inert solvent at a temperature ranging from ice-cold to room temperature. This iodination reaction can also be carried out in a separate step. Step 6-10: Method for producing compound [6-j]: Compound [6-j] can be produced by using compound [6-h] as a starting material and reacting it in an inert solvent at room temperature to 160°C with a palladium catalyst such as tetrakis(triphenylphosphine)palladium(O) and a methylating agent such as methylboronic acid in the presence of a base such as tripotassium phosphate. This methylation reaction can also be carried out in a separate step. Step 6-11: Method for producing compound [6-k]: Compound [6-k] can be produced using compound [6-j] as a starting material by the method described in steps 6-7 above or a similar method. Step 6-12: Method for producing compound [6-m]: Compound [6-m] can be produced using compound [6-k] as a starting material by the method described in step 6-8 above or a similar method. Scheme 6-5 (Separate method for producing compound [6-j] from compound [6-d]):

[0708] [ka] [In the scheme, Alk 3 Alk 4 Alk 6 , and R α2This is the same as the definition above.

[0709] Step 6-13: Method for producing compound [6-n]: Compound [6-n] can be produced by using compound [6-d] as a starting material and reacting it with dichloromethyl methyl ether in an inert solvent at a temperature ranging from ice-cold to room temperature in the presence of a Lewis acid such as titanium(IV) chloride. Note that this formylation reaction can also be carried out in a separate process. Step 6-14: Alternative method for producing compound [6-j]: Compound [6-j] can be produced by using compound [6-n] as a starting material and reacting it with a reducing agent such as triethylsilane in the presence of an acid such as trifluoroacetic acid at temperatures ranging from ice-cold to room temperature. This methylation reaction can also be carried out in a separate step.

[0710] Of the intermediates used in the production of compound [I] of the present invention, compound [2-g] described in production method 2 can be obtained by production by known methods or by purchasing a commercially available product, but it can also be produced by production method 7 or a similar method described below.

[0711] [ka] Manufacturing method 7: A production example of compound [2-g], which is a production intermediate for compound [I] of the present invention, is shown in the following scheme 7. Scheme 7 (Method for producing compound [2-g] from compound [2-b]):

[0712] [ka] [In the scheme, R 2 and LG 1 This is the same as the definition above, PG 2 This shows an amino protecting group such as tert-butoxycarbonyl, PG 3This indicates a hydrogen atom or an amino protecting group such as tert-butoxycarbonyl. Also, PG 2 and PG 3 It can also combine with adjacent nitrogen atoms to form phthalimides, etc., protecting amino acids.

[0713] Step 7-1: Method for producing compound [7-a]: Compound [7-a] can be produced by using compound [2-b] as a starting material and reacting it with potassium phthalimide or di-tert-butyl iminodicarboxylate in an inert solvent at room temperature to 120°C, in or without a base such as potassium carbonate. Step 7-2: Method for producing compound [2-g]: Compound [2-g] can be produced using compound [7-a] as a starting material by any of the following reaction conditions (i) to (ii). (i) Conditions under which an acid such as hydrochloric acid is reacted in an inert solvent at a temperature from ice-cold to 100°C, or (ii) Conditions for reacting hydrazine monohydrate, etc., in an inert solvent at room temperature to reflux temperature

[0714] Compound [2-b] used as a raw material compound in step 7-1 above can be manufactured by a method known to the present day, by the method shown in scheme 4-1 above, or by purchasing a commercially available product.

[0715] The compound [2-g] obtained in this manner can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0716] Of the intermediates used to produce compound [I] of the present invention, compound [2-b] described in scheme 7 can be obtained by manufacturing by methods known to the present invention or by purchasing a commercially available product.

[0717] Among the intermediates used in the production of compound [I] of the present invention, the compound whose structure is represented by formula [1-b] (hereinafter sometimes referred to as compound [1-b]) can also be produced, for example, by the following production method 8 or a similar method.

[0718] [ka] Manufacturing method 8: Compound [1-b], which is a manufacturing intermediate for compound [I] of the present invention, can be obtained by manufacturing by methods known to the present invention or by purchasing a commercially available product, but it can also be manufactured, for example, by the method described in Scheme 8-1 below or a similar method. Scheme 8-1 (Method for producing compound [1-b] from compound [8-a]):

[0719] [ka] [In the scheme, W and Alk 1 This is the same as the definition above, PG 4 This represents an amino protecting group such as benzyloxycarbonyl, tert-butoxycarbonyl, or allyloxycarbonyl.

[0720] Step 8-1: Method for producing compound [8-b]: Compound [8-b] can be produced using compound [8-a] as a starting material by any of the following reaction conditions (i) to (iii). (i) Conditions under which an alkylating agent such as methyl iodide is reacted in an inert solvent at room temperature to reflux temperature, in or without the presence of a base such as potassium carbonate, (ii) Conditions under which an alcohol such as methanol or ethanol is reacted in the presence or absence of an inert solvent, at room temperature to reflux temperature, in the presence of p-toluenesulfonic acid, thionyl chloride, etc., or (iii) Conditions under which an alkylating agent such as methyl iodide is reacted in an inert solvent at room temperature to reflux temperature in the presence of a silver compound such as silver oxide.

[0721] Step 8-2: Method for producing compound [1-b]: Compound [1-b] can be produced using compound [8-b] as a starting material by the following deprotection reactions in an inert solvent: (i) to (iii). (i) Deprotection reaction using acids such as hydrochloric acid, hydrobromic acid, and trifluoroacetic acid at temperatures from ice-cold to 80°C. (ii) Deprotection reaction using palladium carbon, etc., in a hydrogen atmosphere from ice-cold temperature to room temperature, under pressure or without pressure, in the presence or absence of acid, or (iii) Deprotection reaction at ice-cold temperature to 80°C in the presence of an allyl scavenger such as 1,3-dimethylbarbitulic acid, using a palladium catalyst such as tetrakis(triphenylphosphine)palladium(0).

[0722] Compound [8-f], in which W has the structure represented by the aforementioned formula [III-1] in compound [1-b], can be obtained by manufacturing by known methods or by purchasing a commercially available product. Furthermore, this compound can also be produced, for example, by the method described in Scheme 8-2 below or by a similar method.

[0723] [ka] Scheme 8-2 (Method for producing compound [8-f] from compound [8-c]):

[0724] [ka] [In the scheme, Ring A 1 , R A11 , R A12 Alk 1 , and PG 4 This is the same as the definition above.

[0725] Step 8-3: Method for producing compound [8-d]: Starting with compound [8-c], compound [8-d] can be produced by selectively hydrolyzing only one of the two esters of compound [8-c] by reacting it with tetramethylammonium hydroxide, tetraethylammonium hydroxide, etc., in an inert solvent at ice-cold to room temperature. This process can be carried out by referring, for example, to the method described in The Journal of Organic Chemistry, Vol. 82, p. 12863, 2017. Step 8-4: Method for producing compound [8-e]: Starting with compound [8-d], compound [8-e] can be produced by reacting it with an azidating agent such as diphenyl phosphoryl azide in an inert solvent at a temperature from ice-cold to 100°C in the presence of a base such as triethylamine to form the corresponding isocyanate, and then reacting it with an alcohol such as benzyl alcohol, tert-butyl alcohol, or allyl alcohol. Step 8-5: Method for producing compound [8-f]: Compound [8-f] can be produced using compound [8-e] as a starting material by the method described in step 8-2 above or by a similar method.

[0726] Furthermore, compounds [8-f'] and [8-f''] in which W in compound [1-b] has the structure represented by the aforementioned formula [III-2] or [III-3] can be obtained by manufacturing by known methods or by purchasing commercially available products. Furthermore, these compounds can also be produced, for example, by the method described in Scheme 8-2 above or by a similar method.

[0727] [ka] [In the formula, Ring A 2 , ring A 3 , R A21 , R A22 , R A31 , R A32 , and Alk1 This is the same as the definition above.

[0728] In compound [1-b], W is a structure represented by the above formula [III-1], and in that structure, ring A 1 But "hydroxy, C 1-6 C substituted with one group selected from the group consisting of alkoxys and saturated 4-6 member heterocyclines containing a nitrogen atom. 3-8 The cycloalkane compound [8-p] can be obtained by manufacturing by known methods or by purchasing a commercially available product. Furthermore, this compound is, for example, an oxo-substituted C 3-8 It can also be produced using compound [8-g], which is a cycloalkane compound, as a starting material by the method described in Scheme 8-3 below or by a similar method.

[0729] [ka] Scheme 8-3 (Method for producing compound [8-p] from compound [8-g]):

[0730] [ka] [In the scheme, Alk 1 and PG 4 This is the same as the definition above, Ring A 1 ' is C 3-8 It is a cycloalkane, PG 5 C 1-3 It indicates alkyl, Here, Two point guards 5 The carbonyl may be protected by forming a 5-6 membered ring (which may be substituted with 1-2 groups selected from the group consisting of methyl and phenyl) together with the bonded oxygen and carbon atoms. R A11 ' is hydroxy, C 1-6Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C 1-3 It may be substituted with an alkyl group.

[0731] Step 8-6: Method for producing compound [8-h]: Compound [8-h] can be produced by using compound [8-g] as a starting material and reacting it in an inert solvent at room temperature to reflux temperature in the presence of an acid such as p-toluenesulfonic acid with an alcohol such as methanol, ethylene glycol, or hydrobenzoin, or an orthoester such as triethyl orthoformate. Step 8-7: Method for producing compound [8-j]: Compound [8-j] can be produced using compound [8-h] as a starting material by the method described in step 8-3 above or a similar method. Step 8-8: Method for producing compound [8-k]: Compound [8-k] can be produced using compound [8-j] as a starting material by the method described in step 8-4 above or by a similar method. Step 8-9: Method for producing compound [8-m]: Compound [8-m] can be produced by using compound [8-k] as a starting material and carrying out a deprotection reaction with an acid such as hydrochloric acid or trifluoroacetic acid in an inert solvent at room temperature to reflux temperature. Step 8-10: Method for producing compound [8-n]: Compound [8-n] can be produced by using compound [8-m] as a starting material and carrying out one of the following reactions (i) to (iv). (i) A reduction reaction in an inert solvent at a reflux temperature from -80°C, with or without additives such as zinc chloride, using reducing agents such as sodium borohydride, lithium borohydride, diisobutylaluminum hydride, lithium triethylborohydride, lithium tri-sec-butylborohydride, and borane-tetrahydrofuran. (ii) After performing the operation in step 8-10(i), a "hydrolysis reaction" is carried out in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a phosphorus compound such as triphenylphosphine and an azodicarboxylic acid diester such as bis(2-methoxyethyl) azodicarboxylic acid. (iii) After carrying out the operation in step 8-10(i) or 8-10(ii), in an inert solvent, at room temperature to reflux temperature, in the presence of a silver compound such as silver oxide, a reaction using an alkyl halide such as methyl iodide or ethyl iodide, or (iv)R A11 'Reductive amination reaction with the corresponding amine' Steps 8-10(i) described above can be carried out, for example, by referring to the method described in Bioorganic & Medicinal Chemistry, Vol. 17, p. 1982, 2009. Furthermore, in step 8-10(i), compound [8-n] can be produced stereoselectively by selecting an appropriate reducing agent. Step 8-11: Method for producing compound [8-p]: Compound [8-p] can be produced using compound [8-n] as a starting material by the method described in step 8-2 above or by a similar method.

[0732] Furthermore, this compound [8-p] is, for example, obtained in scheme 8-3, oxo-substituted C 3-8 It can also be produced using compound [8-m], which is a cycloalkane compound, as a starting material, by the method described in Scheme 8-4 below or by a similar method. Scheme 8-4 (Method for producing compound [8-p] from compound [8-m]):

[0733] [ka] [In the scheme, Alk 1 PG 4 , ring A 1 ', and R A11 ' is the same as the definition above.' Step 8-12: Method for producing compound [1-b']: Compound [1-b'] can be produced using compound [8-m] as a starting material by the method described in step 8-2 above or a similar method. Step 8-13: Method for producing compound [8-q]: Compound [8-q] can be produced by using compound [1-b'] as a starting material and reacting it with phthalic anhydride or the like in an inert solvent at room temperature to reflux temperature in the presence of a base such as triethylamine. Step 8-14: Method for producing compound [8-r]: Compound [8-r] can be produced using compound [8-q] as a starting material by the method described in step 8-10 above or a similar method. Step 8-15: Method for producing compound [8-p]: Compound [8-p] can also be produced by using compound [8-r] as a starting material and reacting it with an acid such as hydrochloric acid or hydrazine in an inert solvent at a temperature ranging from ice-cold to reflux.

[0734] Furthermore, in compound [1-b], W is a structure represented by the aforementioned formula [III-2] or [III-3], and in that structure, ring A 2 , ring A 3 But "hydroxy, C 1-6 C substituted with one group selected from the group consisting of alkoxys and saturated 4-6 member heterocyclines containing a nitrogen atom. 3-8 The cycloalkane compounds [8-p'] and [8-p''] can be obtained by manufacturing by known methods or by purchasing commercially available products. Furthermore, these compounds can also be produced, for example, by the methods described in schemes 8-3 and 8-4 above, or by similar methods.

[0735] [ka] [In the formula, Alk 1 This is the same as the definition above, Ring A2 'and ring A 3 ' is ring A 1 The same as the definition of ', C 3-8 It is a cycloalkane, R A21 'and R A31 ' is R A11 The same as the definition of ', hydroxy, C 1-6 Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C 1-3 It may be substituted with alkyl.

[0736] In compound [1-b], W is a structure represented by the above formula [III-1], and in that structure, ring A 1 However, C is substituted with one hydroxyl group. 3-8 Compound [8-w] is a cycloalkane, and ring A 1 However, one C 1-6 alkoxy-substituted C 3-8 Compound [8-z], which is a cycloalkane, can be obtained by manufacturing by methods known to the present day or by purchasing a commercially available product. Furthermore, these compounds include, for example, oxo-substituted C 3-8 Compound [8-g], which is a cycloalkane compound, can also be used as a starting material and manufactured by the method described in Scheme 8-5 below or by a similar method. Furthermore, if compounds [8-w] and [8-z] each have corresponding enantiomers or diastereomers, these enantiomers or diastereomers can also be produced by known methods, by the method shown in Scheme 8-5, or by purchasing commercially available products.

[0737] [ka] Scheme 8-5 (Method for producing compounds [8-w] and [8-z] from compound [8-g]):

[0738] [ka] [In the scheme, Alk 1 , ring A 1 ', and PG 4 This is the same as the definition above, R A11a C 1-6 [This indicates an alkoxy.]

[0739] Step 8-16: Method for producing compound [8-s]: Compound [8-s] can be produced using compound [8-g] as a starting material by the method described in step 8-10(i) above or by a similar method. Step 8-17: Method for producing compound [8-t]: Compound [8-t] can be produced using compound [8-s] as a starting material by the method described in step 8-3 above or by a similar method. Step 8-18: Method for producing compound [8-u]: Compound [8-u] can be produced by using compound [8-t] as a starting material and reacting it with an azide such as diphenyl phosphate in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a base such as triethylamine. Steps 8-18 described above can be carried out by referring, for example, to the method described in the Journal of the Organic Chemistry, Vol. 82, p. 12863, 2017. Step 8-19: Method for producing compound [8-v]: Compound [8-v] can be produced by using compound [8-u] as a starting material and reacting it with a base such as potassium hydroxide and water in an inert solvent at a temperature ranging from ice-cold to reflux. Step 8-20: Method for producing compound [8-w]: Compound [8-w] can also be produced using compound [8-v] as a starting material by the method described in step 8-1(ii) above or a similar method. Step 8-21: Method for producing compound [8-x]: Compound [8-x] can be produced by using compound [8-w] as a starting material and reacting it with di-tert-butyl dicarbonate, allyl chloroformate, benzyl chloroformate, etc., in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a base such as triethylamine, sodium hydroxide, or sodium carbonate. Step 8-22: Method for producing compound [8-y]: Compound [8-y] can be produced by using compound [8-x] as a starting material and reacting it with an alkyl halide such as methyl iodide or ethyl iodide in an inert solvent at room temperature to reflux temperature in the presence of a silver compound such as silver oxide. Step 8-23: Method for producing compound [8-z]: Compound [8-z] can also be produced using compound [8-y] as a starting material by the method described in step 8-2 above or a similar method.

[0740] In compound [1-b], W is a structure represented by the above formula [III-1], and in that structure, ring A 1 is "C 1-4 Alkylcarbonyl and C 1-4 Compounds [8-ac], which are 4- to 8-membered saturated heterocycles containing a nitrogen atom substituted with one group selected from the group consisting of "alkoxycarbonyls," can be manufactured by methods known to the present day or obtained by purchasing commercially available products. Furthermore, this compound can also be produced using compound [8-aa], for example, a saturated heterocyclic compound with 4 to 8 members containing a nitrogen atom, as a starting material, by the method described in scheme 8-6 below or a similar method.

[0741] [ka] Scheme 8-6 (Method for producing compound [8-ac] from compound [8-aa]):

[0742] [ka] [In the scheme, Alk 1 and PG 4 This is the same as the definition above, Ring A 1 " is a saturated heterocycle with 4 to 8 members containing a nitrogen atom, R A11 " is C 1-4 Alkylcarbonyl or C 1-4 [This indicates an alkoxycarbonyl group.] Step 8-24: Method for producing compound [8-ac]: Compound [8-ab] can be produced by using compound [8-aa] as a starting material and carrying out the following reaction (i) or (ii). (i) In an inert solvent, at a temperature from ice-cold to 50°C, in the presence of a base, R such as acetyl chloride is used. A11″ Corresponding to R such as acylchloride or acetic anhydride A11″ Reactions using the corresponding acid anhydride, or (ii) In an inert solvent, at a temperature from ice-cold to 50°C, in the presence or absence of a base, R such as ethyl chloroformate A11″ Reactions using chloroformate esters corresponding to these reactions Step 8-25: Method for producing compound [8-ac]: Compound [8-ac] can be produced using compound [8-ab] as a starting material by the method described in step 8-2 above or by a similar method.

[0743] Furthermore, in compound [1-b], W is a structure represented by the aforementioned formula [III-2] or [III-3], and in that structure, ring A 2 , ring A 3 is "C 1-4 Alkylcarbonyl and C 1-4 Compounds [8-ac'], [8-ac''], which are 4- to 8-membered saturated heterocycles containing a nitrogen atom substituted with one group selected from the group consisting of "alkoxycarbonyls", can be manufactured by methods known to the present day or obtained by purchasing commercially available products. Furthermore, these compounds can also be produced, for example, by the method described in Scheme 8-6 above or by a similar method.

[0744] [ka] [In the formula, Alk 1 This is the same as the definition above, Ring A 2” and ring A 3” is ring A 1” It is the same as the definition, a saturated heterocycle with 4 to 8 members containing a nitrogen atom, R A21 "and R A31 " is R A11 This is the same as the definition of C 1-4 Alkylcarbonyl or C 1-4 It is an alkoxycarbonyl compound.

[0745] The compounds obtained in this way, [1-b], [8-f], [8-f'], [8-f''], [8-p], [8-p'], [8-p''], [8-w], [8-z], [8-ac], [8-ac'], and [8-ac''], can be isolated and purified by known separation and purification methods, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0746] Among the intermediates used in the production of compound [I] of the present invention, compound [8-a] described in scheme 8-1, compound [8-c] described in scheme 8-2, compound [8-g] described in schemes 8-3 and 8-5, and compound [8-aa] described in scheme 8-6 can be obtained by manufacturing by methods known to the public or by purchasing commercially available products.

[0747] Among the compounds [I] of the present invention, compounds in which X is carbamoyl, compounds in which X is a group represented by the following formulas [II-2], [II-3], [II-4], [II-5], or [II-1], and compounds in which X is tetrazolyl can be produced, for example, by the following production method 9 or a similar method.

[0748] [ka]

[0749] A production example of compound [9-a] of the present invention, in which X is a carbamoyl or a group represented by formulas [II-2], [II-3], or [II-4], is shown in the following scheme 9-1. Manufacturing method 9: Scheme 9-1 (Method for producing compound [9-a] from compound [1-d]):

[0750] [ka] [In the scheme, R 1 , R 2 , R 3 , R 4 , and W are the same as defined above, EQ 1 is a hydrogen atom or a group selected from the following formula group [II']

[0751] [ka] [This indicates...]

[0752] Step 9-1: Method for producing [9-a]: Compound [9-a] can be produced by reacting compound [1-d] as a starting material with an amine compound such as methanesulfonamide, sulfamide, N,N-dimethylsulfamide, or ammonium chloride in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence or absence of a base such as N,N-diisopropylethylamine, in the presence or absence of an additive such as 4-dimethylaminopyridine or HOBt, and in the presence of a condensing agent such as EDC or CDI.

[0753] A production example of compound [9-h] of the present invention, in which X is a group represented by formula [II-5], is shown in the following scheme 9-2. Scheme 9-2 (Method for producing compound [9-h] from compound [9-b]):

[0754] [ka] [In the scheme, R 2 , R 3 , R 4 , R A11 and R A12 This is the same as the definition above, Ring D is C 3-8 This represents a cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, or a 4-8 membered saturated heterocycle containing a nitrogen atom. Here, The sulfur atom in the 4-8 member saturated heterocycle containing the sulfur atom may be substituted with 1-2 oxos. The nitrogen atom in the saturated heterocycle of 4 to 8 members containing the nitrogen atom is C 1-4 Alkylcarbonyl and C 1-4 It may be substituted with one group selected from the group consisting of alkoxycarbonyls. PG 5 This indicates a protecting group for phosphate groups such as benzyl, PG 6 This indicates an amino protecting group such as diphenylmethyl.

[0755] Step 9-2: Method for producing compound [9-e]: Compound [9-e] can be produced by using compounds [9-b], [9-c], and [9-d] as starting materials and reacting them with a Lewis acid such as bismuth(III) chloride in an inert solvent at room temperature to 120°C. This process can be carried out by referring, for example, to the method described in Organic Letters, Vol. 1, p. 1395, 1999. Furthermore, this reaction can also be carried out under microwave irradiation. Step 9-3: Method for producing compound [9-f]: Starting with compound [9-e], compound [9-f] can be produced by reacting it with an oxidizing agent such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in an inert solvent at room temperature to 100°C to form the corresponding imine, and then reacting it with an acidic aqueous solution such as hydrochloric acid in an inert solvent at room temperature to 60°C. This process can be carried out by referring, for example, to the method described in Organic Letters, Vol. 1, p. 1395, 1999. Step 9-4: Method for producing compound [9-g]: Compound [9-g] can be produced by reacting compound [1-a] with compound [9-f] as a starting material in an inert solvent at a temperature ranging from ice-cold to reflux, in the presence of a base such as triethylamine, pyridine, 4-dimethylaminopyridine, and N,N-diisopropylethylamine, and a urea-forming agent such as 4-nitrophenyl chloroformate, CDI, or triphosgene. Step 9-5: Method for producing compound [9-h]: Compound [9-h] can be produced by using compound [9-g] as a starting material and carrying out a deprotection reaction using palladium carbon, etc., in an inert solvent at ice-cold temperatures to room temperature, in a hydrogen atmosphere under pressure or without pressure, in the presence or absence of an acid.

[0756] A production example of compound [9-r] of the present invention, in which X is a group represented by formula [II-1], is shown in the following scheme 9-3. Scheme 9-3 (Method for producing compound [9-q] from compound [8-a]):

[0757] [ka] [In the scheme, PG 4 , R 2 , R 3 , R 4 , and W are the same as defined above.

[0758] Step 9-6: Method for producing compound [9-j]: Compound [9-j] can be produced by carrying out a "condensation reaction" between compound [8-a] and an amine compound such as ammonium chloride. Step 9-7: Method for producing compound [9-k]: Starting with compound [9-j], in an inert solvent at a temperature from ice-cold to 50°C, in the presence of a base such as pyridine, an aryl sulfonyl chloride such as p-toluenesulfonyl chloride or a C such as methanesulfonyl chloride is added. 1-4 Compound [9-k] can be produced by reacting it with alkyl sulfonyl chloride. Step 9-8: Method for producing compound [9-m]: Compound [9-m] can be produced using compound [9-k] as a starting material by the method described in step 8-2 above or by a similar method. Step 9-9: Method for producing compound [9-n]: Compound [9-n] can be produced using compound [9-m] as a starting material by the method described in step 9-4 above or by a similar method. Steps 9-10: Method for producing compound [9-p]: Compound [9-p] can be produced by using compound [9-n] as a starting material and reacting it with hydroxylamine hydrochloride in an inert solvent at a temperature from ice-cold to 90°C, in the presence or absence of a base such as sodium carbonate or N,N-diisopropylethylamine. Steps 9-11: Method for producing compound [9-q]: Compound [9-q] can be produced by reacting compound [9-p] as a starting material with CDI, etc., in an inert solvent at a temperature ranging from ice-cold to room temperature, in the presence of a base such as 1,8-diazabicyclo[5.4.0]-7-undecene.

[0759] A production example of compound [9-v] of the present invention, in which X is tetrazolyl, is shown in the following scheme 9-4. Scheme 9-4 (Method for producing compound [9-v] from compound [9-k]):

[0760] [ka] [In the scheme, PG 4 , R 2 , R 3 , R 4 , and W are the same as defined above, PG 7 This indicates a tetrazolyl protecting group such as triphenylmethyl or benzyl.

[0761] Steps 9-12: Method for producing compound [9-r]: Compound [9-r] can be produced by using compound [9-k] as a starting material and reacting it with an azide such as sodium azide in an inert solvent at room temperature to 150°C in the presence of an inorganic salt of an amine compound such as ammonium chloride or trimethylamine hydrochloride, and in or without a copper catalyst. This reaction can also be carried out under microwave irradiation. Steps 9-13: Method for producing compound [9-s]: Compound [9-s] can be produced by using compound [9-r] as a starting material and reacting it with trityl chloride, benzyl bromide, etc., in an inert solvent at ice-cold temperatures to room temperature in the presence of a base such as triethylamine or potassium carbonate. Steps 9-14: Method for producing compound [9-t]: Compound [9-t] can be produced using compound [9-s] as a starting material by the method described in step 8-2 above or by a similar method. Steps 9-15: Method for producing compound [9-u]: Compound [9-u] can be produced using compound [9-t] as a starting material by the method described in step 9-4 above or by a similar method. Steps 9-16: Method for producing compound [9-v]: Compound [9-v] can be produced by using compound [9-u] as a starting material and reacting it with an acid such as hydrochloric acid in an inert solvent at a temperature ranging from ice-cold to room temperature (i) or by a deprotection reaction using palladium carbon, etc., in a hydrogen atmosphere under or without pressure, in or without the presence of an acid.

[0762] The compounds [9-a], [9-h], [9-q], and [9-v] obtained in this manner can be isolated and purified by separation and purification means, such as concentration, vacuum concentration, reprecipitation, solvent extraction, crystallization, and chromatography.

[0763] Among the intermediates used in the production of compound [I] of the present invention, compounds [9-b], [9-c], [9-d] described in scheme 9-2, and compound [8-a] described in scheme 9-3 can be obtained by manufacturing by methods known to the present invention or by purchasing commercially available products.

[0764] The present invention will be further described in detail by the following reference examples, examples, and test examples, but these will not limit the present invention and may be modified without departing from the scope of the present invention. Furthermore, in the following reference examples and implementations, the yield may exceed the theoretical amount due to the influence of residual solvents, etc.

[0765] In the following reference examples and examples, packed columns (Reveleris® Flash Cartridges Silica from Grace or Biotage® SNAP Cartridge HP-Sphere from Biotage) were used for silica gel column chromatography. Packed columns (Reveleris® Flash Cartridges Amino from Grace or Biotage® SNAP Cartridge KP-NH from Biotage) were used for NH silica gel column chromatography. For preparative thin-layer chromatography, a Merck PLC plate 20x20cm silica gel 60F 254.2mm was used. Unless otherwise specified, the ratio of elution solvents is given as a volume ratio. A Biotage ISOLUTE® Phase Separator was used.

[0766] The abbreviations used in this specification have the following meanings: s: singlet d: doublet t: triplet q: quartet quintet sxt: sextet spt: Septet dd: double doublet dt: double triplet td: Triple doublet tt: Triple triplet qd: quarter doublet m: multiplet br : broad J: Coupling constant Hz: Hertz CHLOROFORM-d: Deuterated chloroform DMSO-d6: Deuterated Dimethyl Sulfoxide METHANOL-d4: Heavy methanol ACETONE-d6: Heavy acetone D2O: heavy water

[0767] HATU: O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate EDC: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride CDI: 1,1'-Carbonyldiimidazole DMT-MM: 4-(4,6-dimethoxy-1,3,5-triazine-2-yl)-4-methylmorpholinium chloride HOBt: N-hydroxybenzotriazole monohydrate DBU: 1,8-Diazabicyclo[5.4.0]-7-Undecene

[0768] Rf: Retardation factor posi: positive (mode) nega: negative (mode)

[0769] 1 ¹H-NMR (proton nuclear magnetic resonance spectroscopy) was measured using the following Fourier transform NMR with tetramethylsilane as an internal standard, and the total δ values ​​are shown in ppm. 200MHz: Gemini2000 (Agilent Technologies) 300MHz: Inova300 (Agilent Technologies) 400MHz: AVANCE III HD400 (Bruker) 500MHz: JNM-ECA500 (JEOL) 600MHz: JNM-ECA600 (JEOL) The analysis was performed using ACD / Spectrus Processor 2015 ACD / Labs 2015 Release (File Version S30S41, Build 76327, 28 Feb 2015) (product name), etc. Peaks with very gradual proton formation, such as hydroxyl, amino, amide, pyrazole, urea, and carboxyl, may not be described. In addition, during the analysis of compounds, there may be protons that are not identified because they overlap with the water or solvent peaks.

[0770] Mass spectroscopy (MS) was measured using the following equipment. PlatformLC (Waters) LCMS-2010EV (Shimadzu) LCMS-IT-TOF (Shimadzu) Agilent 6130 (Agilent) Agilent 6150 (Agilent) The ionization methods used were ESI (Electrospray Ionization), EI (Electron Ionization), or a dual ionization method combining ESI and APCI (Atmospheric Pressure Chemical Ionization). The data listed are the measured values ​​(found). Typically, molecular ion peaks are observed, but in the case of compounds containing tert-butoxycarbonyl (-Boc), peaks representing the elimination of tert-butoxycarbonyl or tert-butyl may also be observed as fragment ions. Similarly, in the case of compounds containing tetrahydropyranyl (THP), peaks representing the elimination of tetrahydropyranyl may also be observed as fragment ions. Furthermore, in the case of compounds containing hydroxyl (-OH), peaks representing the elimination of H2O or OH radicals may also be observed as fragment peaks. In the case of salts, typically, the molecular ion peak of the free form or a fragment ion peak is observed. Regarding the measurement conditions for the analysis data, the following conditions were indicated as "mode M". Equipment: LCMS-IT-TOF (Shimadzu) Ionization method: ESI / APCI dual mode

[0771] LC-MS measurements in the examples and reference examples were performed under the following conditions. HPLC: Agilent 1290 Infinity MS: Agilent 6130 or 6150 [HPLC conditions] Column: Acquity UPLC CSH C18, 1.7 μm, 2.1 x 50 mm (WATERS) Solvents: Solution A; 0.1% formic acid-containing water; Solution B; 0.1% formic acid-containing acetonitrile

[0772] (Method A, Normal mode) Gradient: 0.00 min (Solution A / Solution B = 80 / 20), 1.20 min (Solution A / Solution B = 1 / 99), 1.40 min (Solution A / Solution B = 1 / 99), 1.41 min (Solution A / Solution B = 80 / 20), 1.50 min (Solution A / Solution B = 80 / 20) (Method B, HP Mode) Gradient: 0.00 min (A / B = 95 / 5), 0.80 min (A / B = 60 / 40), 1.08 min (A / B = 1 / 99), 1.38 min (A / B = 1 / 99), 1.41 min (A / B = 95 / 5), 1.50 min (A / B = 80 / 20) (Method C, LP mode) Gradient: 0.00 min (Solution A / Solution B = 70 / 30), 0.80 min (Solution A / Solution B = 1 / 99), 1.40 min (Solution A / Solution B = 1 / 99), 1.42 min (Solution A / Solution B = 70 / 30), 1.50 min (Solution A / Solution B = 70 / 30)

[0773] Injection volume: 0.5μL, flow rate: 0.8mL / min Detection method: UV 210nm, 254nm If an evaporative light scattering detector (ELSD) is included, it is called Agilent 385-ELSD. MS conditions Ionization method: ESI or ESI / APCI dual mode The measurement conditions for the analysis data were described as follows:

[0774] [Table 1-1]

[0775] Purification by preparative HPLC in the examples and reference examples was performed under the following conditions. Equipment: Gilson High-Throughput Refining System Column: Triart C18, 5μm, 30x50mm (YMC), or X-Bridge Prep C18 5um OBD, 30x50mm (Waters) Solvent: Solution A; 0.1% formic acid-containing water, Solution B; 0.1% formic acid-containing acetonitrile, or Solution A; 0.1% trifluoroacetic acid-containing water, Solution B; 0.1% trifluoroacetic acid-containing acetonitrile

[0776] (Method A) Gradient: 0.00 min (A / B = 90 / 10), 2.00 min (A / B = 90 / 10), 11.0 min (A / B = 20 / 80), 12.0 min (A / B = 5 / 95), 13.52 min (A / B = 5 / 95), 15.0 min (A / B = 90 / 10) (Method B) Gradient: 0.00 min (A / B = 95 / 5), 3.00 min (A / B = 95 / 5), 8.53 min (A / B = 80 / 20), 10.0 min (A / B = 80 / 20), 11.0 min (Liquid A / Liquid B = 50 / 50), 12.02 minutes (Liquid A / Liquid B = 5 / 95), 13.5 minutes (Liquid A / Liquid B = 5 / 95), 13.65 minutes (Liquid A / Liquid B = 95 / 5), 15.0 minutes (Liquid A / Liquid B = 95 / 5) (Method C) Gradient: 0.00 min (Liquid A / B = 80 / 20), 2.00 min (Liquid A / B = 80 / 20), 10.0 min (Liquid A / B = 5 / 95), 11.0 min (Liquid A / Liquid B = 1 / 99), 13.5 minutes (Liquid A / Liquid B = 1 / 99), 13.55 minutes (Liquid A / Liquid B = 80 / 20), 15.0 minutes (Liquid A / Liquid B = 80 / 20)

[0777] Flow rate: 40mL / min Detection method: UV210nm, UV254nm If ELSD is included: SofTA MODEL 300S ELSD

[0778] In the following examples, diastereomer separation was performed by preparative HPLC. [HPLC conditions]

[0779] [Table 2-1] Detection method: UV 210nm, 254nm

[0780] Chiral HPLC preparative separation in the examples was performed under the following conditions. HPLC: Gilson high-throughput purification system or Waters preparative LC system [HPLC conditions]

[0781] [Table 3-1]

[0782] [Table 3-2]

[0783] [Table 3-3] Detection method: UV 210nm, 254nm

[0784] Chiral supercritical fluid chromatography (SFC) preparative fractionation in the examples was performed under the following conditions. SFC: SFC30 manufactured by WATERS Corporation [SFC conditions]

[0785] [Table 4-1] Detection method: UV 210nm, 254nm

[0786] The optical rotation measurement system used was the Autopol V manufactured by Rudolph Research Analytical, with sodium D-line (589 nm) used as the light source.

[0787] For X-ray crystal structure analysis, we used the R-AXIS RAPIDII instrument (manufacturer: Rigaku).

[0788] The microwave reaction system used was either a Biotage Initiator or an Anton-Paar MONOWAVE300.

[0789] Differential thermal analysis / thermal mass measurement (TG / DTA) is performed using the Thermo Plus Evo TG8. Measured at 120 (Rigaku).

[0790] The compound names were determined using ACD / Name (ACD / Name 2017.1.3 and ACD / Name 2019.1.2, Advanced Chemistry Development, Inc.) and LexiChem (version 0.95), a component of PipelinePilot 9.1 manufactured by OpenEye.

[0791] In the compounds of the Reference Examples and Examples, the stereostructures shown herein represent the absolute configuration of the chiral carbon. For the meso compound, the relative configuration is shown. Compounds in which the absolute configuration of the chiral carbon is indicated are optically active. Furthermore, in compounds where an asterisk (*) is indicated on a chiral carbon in the structural formula, the asterisk indicates that, with respect to the stereoisomerism at the indicated chiral carbon, one absolute configuration is more prominent. It is preferable that such compounds have substantially a single absolute configuration. The absolute configuration of the chiral carbon may also be unknown.

[0792] In this specification, "room temperature" refers to 20-30°C unless otherwise specified. "Ice-cold temperature" refers to 0-5°C unless otherwise specified.

[0793] The present invention will be further described in detail by the following reference examples, examples, and test examples, but these will not limit the present invention and may be modified without departing from the scope of the present invention.

[0794] Reference example 1-1-1 Methyl 3-methoxy-5-(methoxymethyl)benzoate

[0795] [ka] Potassium carbonate (168 mg) was added to a methanol-tetrahydrofuran mixed solution (2.9 mL-2.9 mL) of methyl 3-(bromomethyl)-5-methoxybenzoate (150 mg), and the mixture was stirred overnight at room temperature at 55°C for 3 hours. The reaction mixture was filtered through Celite®, and the filtrate was concentrated to obtain a mixture (327 mg) containing the title compound as a colorless solid. MS ESI posi: 211[M+H] + . Retention time: 0.912 min (method B) Reference example 1-1-2 Ethyl 6-ethoxy-1-ethyl-2,3-dihydro-1H-indole-4-carboxylate

[0796] [ka] (1) A solution of ethyl 6-ethoxy-1H-indole-4-carboxylate (0.488 g) in N,N-dimethylformamide (4.2 mL) was cooled on ice, sodium hydride (60% mineral oil dispersion, 92.0 mg) was added, and the mixture was stirred at the same temperature for 30 minutes. A solution of iodoethane (0.254 mL) in N,N-dimethylformamide (3 mL) was added dropwise, and the mixture was stirred for 30 minutes while returning to room temperature. The reaction mixture was cooled on ice, saturated ammonium chloride aqueous solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ ethyl acetate only) to obtain ethyl 6-ethoxy-1-ethyl-1H-indole-4-carboxylate (0.402 g) as a colorless powder. (2) Sodium borohydride (0.144 g) was slowly added to a solution of the compound obtained in (1) (0.2 g) in acetic acid (1 mL), and the mixture was stirred at room temperature for 1 hour. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 80:20) to obtain the title compound (0.142 g) as a pale yellow oily substance. MS ESI posi: 264[M+H] + . Retention time: 1.264 min (method B) Reference example 1-2-1 Methyl 3,5-diethoxy-2,4-dimethylbenzoate

[0797] [ka] (1) To a solution of methyl 3,5-dihydroxy-4-methylbenzoate (5 g) in N,N-dimethylformamide (55 mL), potassium carbonate (3.79 g) and iodoethane (2.66 mL) were added and the mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture and extracted with a mixed solvent of n-hexane and ethyl acetate (2:1). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 70:30) to obtain methyl 3,5-diethoxy-4-methylbenzoate (2.16 g) and methyl 3-ethoxy-5-hydroxy-4-methylbenzoate (2.02 g), respectively, as colorless powders. (2) Under a nitrogen atmosphere, the chloroform (0.8 mL) solution of methyl 3,5-diethoxy-4-methylbenzoate (0.5 g) obtained in (1) above was cooled on ice, and titanium(IV) chloride (0.506 mL) was added dropwise. The mixture was stirred at the same temperature for 30 minutes, and dichloromethyl methyl ether (0.187 mL) was added dropwise. Chloroform (0.8 mL) was added to the reaction mixture, and the mixture was stirred for 30 minutes while returning to room temperature. Saturated ammonium chloride aqueous solution was added to the reaction mixture, the mixture was stirred for 1 hour, water was added, and the mixture was extracted with chloroform. The organic layer was sequentially washed with 0.1 mol / L hydrochloric acid, saturated sodium bicarbonate aqueous solution, and saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 85:15) to obtain methyl 3,5-diethoxy-2-formyl-4-methylbenzoate (0.527 g) as a yellow oily substance. (3) A solution of the compound obtained in (2) above (0.1 g) in trifluoroacetic acid (0.3 mL) was mixed with triethylsilane (0.72 mL) and stirred at room temperature for 1 hour. Water was added to the reaction mixture and extracted with chloroform. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 80:20) to obtain the title compound (0.062 g) as a colorless oily substance. MS ESI posi: 253[M+H] + . Retention time: 1.057 min (method A) Reference example 1-2-2 Methyl 3,5-diethoxy-2-fluoro-4-methylbenzoate

[0798] [ka] Under a nitrogen atmosphere, a solution of methyl 3,5-diethoxy-4-methylbenzoate (0.5 g) obtained in Reference Example 1-2-1(1) in acetonitrile (1.0 mL) was cooled on ice, and a solution of N-fluoro-N'-(chloromethyl)triethylenediaminebis(tetrafluoroborate) (1.12 g) in acetonitrile (21 mL) was added. The mixture was stirred at room temperature for 23 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 90:10) to obtain the title compound (0.32 g) as a yellow oily substance. MS ESI posi: 257[M+H] + , 279[M+Na] + . Retention time: 0.953 min (method A) Reference example 1-2-3 Ethyl 2-chloro-3,5-diethoxy-4-methylbenzoate

[0799] [ka] (1) N-chlorosuccinimide (1.75 g) was added to a methanol (30 mL) solution of 3,5-dihydroxy-4-methylbenzoic acid (2 g) and stirred at 60°C for 4 hours and at room temperature for 15 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated to obtain 2-chloro-3,5-dihydroxy-4-methylbenzoic acid (2.55 g) as a pale yellow powder. (2) To a solution of the compound obtained in (1) above (2.41 g) and potassium carbonate (8.22 g) in N,N-dimethylformamide (24 mL), iodoethane (4.81 mL) was added and the mixture was stirred at room temperature for 18 hours. Water was added to the reaction mixture and extracted with a mixed solvent of n-hexane-ethyl acetate (2:1). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 90:10) to obtain the title compound (2.99 g) as a colorless oily substance. MS ESI posi: 287[M+H] + ,309[M+Na] + . Retention time: 1.023 min (method A) Reference example 1-3-1 3-Ethoxy-5-(methoxymethyl)-4-methylbenzoic acid

[0800] [ka] (1) Under a nitrogen atmosphere, pyridine (0.23 mL) and trifluoromethanesulfonic anhydride (0.288 mL) were added to a chloroform (5.7 mL) solution of methyl 3-ethoxy-5-hydroxy-4-methylbenzoate (300 mg) obtained in Reference Example 1-2-1(1), and the mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure, and the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5~20:80) to obtain methyl 3-ethoxy-4-methyl-5-[(trifluoromethanesulfonyl)oxy]benzoate (450 mg) as a colorless oily substance. (2) This reaction was carried out based on the method described in the literature (Organic Letters, Vol. 14, p. 1278, 2012). Under a nitrogen atmosphere, sodium carbonate (0.186 g), potassium (acetoxymethyl) trifluoroborate (0.316 g), and (2-dicyclohexylphosphino-2',6'-diisopropoxy-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (RuPhosPdG3, Sigma-Aldrich, 97.7 mg) were added to a 1,4-dioxane-water mixed solution (2 mL-0.2 mL) of the compound obtained in (1) above (400 mg), and the mixture was stirred at 100 °C for 5 hours. The solvent was removed under reduced pressure, and the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5~20:80) to obtain methyl 3-ethoxy-5-(hydroxymethyl)-4-methylbenzoate (250 mg) as a colorless oily substance. (3) To a solution of the compound obtained in (2) above (250 mg) in tetrahydrofuran (11 mL), sodium hydride (60% mineral oil dispersion, 67 mg) was added and the mixture was stirred under ice for 1 hour. Iodomethane (0.1 mL) was added and the mixture was stirred overnight at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed sequentially with water and saturated brine, and anhydrous magnesium sulfate was added. The drying agent was filtered off and the mixture was concentrated. The residue was purified by silica gel column chromatography (n-hexane only to ethyl acetate only) to obtain methyl 3-ethoxy-5-(methoxymethyl)-4-methylbenzoate (84 mg) as a brown oily substance. (4) To a solution of the compound obtained in (3) above (84 mg) in tetrahydrofuran (3.5 mL), 1 mol / L aqueous sodium hydroxide solution (3.5 mL) and methanol (1.8 mL) were added and the mixture was stirred at 60°C for 30 minutes. The reaction mixture was concentrated, 1 mol / L hydrochloric acid was added to make it acidic, and it was extracted with chloroform. The organic layer was filtered through a phase separator and concentrated to obtain the title compound (85 mg) as a colorless powder. MS ESI posi: 225[M+H] + . MS ESI nega: 223[MH] - . Retention time: 1.128 min (method B) Reference example 1-4-1 4-Bromo-3,5-dimethoxybenzaldehyde

[0801] [ka] (1) A solution of 4-bromo-3,5-dimethoxybenzoic acid (3.0 g) in tetrahydrofuran (7.7 mL) was cooled on ice, and borane-tetrahydrofuran complex (0.9 mol / L tetrahydrofuran solution, 20 mL) was slowly added. The mixture was stirred at the same temperature for 30 minutes, and then stirred at room temperature for 2 hours. The reaction mixture was cooled on ice, saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted with ethyl acetate. The organic layer was filtered through a phase separator and concentrated to obtain (4-bromo-3,5-dimethoxyphenyl)methanol (2.8 g) as a colorless powder. (2) To a solution of the compound obtained in (1) above (2.3 g) in toluene (62 mL), manganese dioxide (8.1 g) was added and the mixture was stirred at room temperature for 16 hours. The reaction mixture was filtered through Celite®, and the filtrate was concentrated to obtain the title compound (2.18 g) as a pale yellow powder. MS ESI posi: 254[M+H] + . Retention time: 0.996 min (method B) Reference example 1-4-2 3,5-Diethoxy-4-methylbenzaldehyde

[0802] [ka] (1) A solution of methyl 3,5-diethoxy-4-methylbenzoate (1.1 g) obtained in Reference Example 1-2-1(1) in tetrahydrofuran (18 mL) was cooled on ice, lithium aluminum hydride (0.26 g) was added, and the mixture was stirred at room temperature for 1 hour. Sodium sulfate decahydrate (3 g) was added, and the mixture was stirred for 2 hours. The reaction mixture was filtered through Celite®, and the filtrate was concentrated to obtain (3,5-diethoxy-4-methylphenyl)methanol (0.98 g) as a pale yellow solid. (2) Using the compound obtained in (1) above (0.98 g), the reaction and workup were carried out in accordance with the method described in Reference Example 1-4-1(2), and the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5~60:40) to obtain the title compound (205 mg) as a yellow solid. MS ESI posi: 209[M+H] + . Retention time: 1.196 min (method B)

[0803] The following Reference Examples 1-4-3 to 1-4-6 were synthesized using commercially available compounds or compounds obtained by methods described in the literature or similar methods, using the methods described in Reference Example 1-4-1 or Reference Example 1-4-2 or similar methods. The structures and LCMS data of the compounds are shown in Table 5-1.

[0804] [Table 5-1] Reference example 1-5-1 1-(4-bromo-3,5-diethoxyphenyl)ethane-1-one

[0805] [ka] (1) Using 4-bromo-3,5-dihydroxybenzoic acid (4 g), the reaction and workup were carried out according to the method described in Reference Example 1-2-3(2). A mixed solution of n-hexane and ethyl acetate (4:3, 7 mL) was added to the obtained residue to dissolve it, and then n-hexane (12 mL) was added. The precipitated solid was filtered off, and the filtrate was concentrated. Ethyl acetate (3 mL) was added to the obtained residue to dissolve it, and then n-hexane (16 mL) was added, and the precipitated solid was filtered off. The obtained solids were combined to obtain ethyl 4-bromo-3,5-diethoxybenzoate (5.11 g) as a colorless solid. (2) Using the compound obtained in (1) above (5.11 g), the reaction was carried out in accordance with the method described in Reference Example 1-3-1(4) to obtain 4-bromo-3,5-diethoxybenzoic acid (4.68 g) as a colorless solid. (3) To a solution of the compound obtained in (2) above (4.68 g) in N,N-dimethylformamide (26 mL), N,O-dimethylhydroxylamine hydrochloride (1.65 g), HATU (9.19 g), and N,N-diisopropylethylamine (11.2 mL) were added and the mixture was stirred at room temperature for 3 hours. A saturated aqueous sodium bicarbonate solution (150 mL) was added to the reaction mixture and extracted twice with a mixed solvent of n-hexane and ethyl acetate (2:1, 100 mL). The organic layer was washed with saturated saline solution, filtered through a phase separator, and concentrated. The resulting residue was purified by NH silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 60:40) to obtain 4-bromo-3,5-diethoxy-N-methoxy-N-methylbenzamide (6.2 g) as a pale yellow oily substance. (4) Under a nitrogen atmosphere, a solution of the compound obtained in (3) above (5.36 g) in tetrahydrofuran (54 mL) was cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 16.1 mL) was added, and the mixture was stirred at the same temperature for 30 minutes and at room temperature for 4.5 hours. The reaction mixture was cooled on ice, saturated ammonium chloride aqueous solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. A mixed solvent of n-hexane-ethyl acetate (2:1, 60 mL) was added to the resulting residue, and the precipitated solid was filtered off to obtain the title compound (3.18 g) as a colorless solid. MS ESI posi: 287, 289[M+H] + . Retention time: 1.149 min (method B) Reference example 1-5-2 1-(3,5-diethoxy-4-methylphenyl)ethane-1-one

[0806] [ka] (1) Using 3,5-dihydroxy-4-methylbenzoic acid (3 g), the reaction was carried out according to the method described in Reference Example 1-2-3(2) to obtain ethyl 3,5-diethoxy-4-methylbenzoate (4.45 g) as a light brown solid. (2) Using the compound obtained in (1) above (4.2 g), the reaction was carried out in accordance with the method described in Reference Example 1-3-1(4) to obtain 3,5-diethoxy-4-methylbenzoic acid (3.74 g) as a colorless powder. (3) This reaction was carried out with reference to the method described in the literature (Synlett, Vol. 26, p. 1395, 2015). Under a nitrogen atmosphere, a solution of the compound obtained in (2) above (3.7 g) in diethyl ether (130 mL) was cooled on ice, methyl lithium (1 mol / L diethyl ether solution, 50 mL) was added, and the mixture was stirred overnight at room temperature for 10 minutes at the same temperature. The reaction mixture was cooled on ice, water was slowly added, and the mixture was acidified with 2 mol / L hydrochloric acid. The mixture was stirred for 30 minutes and extracted three times with diethyl ether. The organic layer was sequentially washed with saturated sodium bicarbonate aqueous solution (60 mL) and saturated brine (60 mL), filtered using a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 88:12 - ethyl acetate only) to obtain the title compound (2.0 g) as a colorless powder. MS ESI posi: 223[M+H] + . Retention time: 0.931 min (method A)

[0807] The following Reference Examples 1-5-3 to 1-5-30 were synthesized using the methods described in Reference Examples 1-1-1 to 1-1-2, Reference Examples 1-2-1 to 1-2-3, and Reference Example 1-3-1, commercially available compounds, or compounds synthesized according to methods described in the literature or similar methods, using the methods described in Reference Example 1-5-1 or Reference Example 1-5-2 or similar methods. The structures and LCMS data of the compounds are shown in Tables 6-1 to 6-6.

[0808] [Table 6-1]

[0809] [Table 6-2]

[0810] [Table 6-3]

[0811] [Table 6-4]

[0812] [Table 6-5]

[0813] [Table 6-6] Reference example 1-6-1 1-(4-bromo-3,5-dimethoxyphenyl)ethane-1-one

[0814] [ka] (1) A solution of the compound obtained in Reference Example 1-4-1 (506 mg) in tetrahydrofuran (4.1 mL) was cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 688 μL) was added, and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was cooled on ice, saturated ammonium chloride aqueous solution (5 mL) was added, extracted with chloroform, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5~35:65) to obtain 1-(4-bromo-3,5-dimethoxyphenyl)ethane-1-ol (443 mg) as a colorless solid. (2) Using the compound obtained in (1) above (443 mg), the reaction was carried out in accordance with the method described in Reference Example 1-4-1(2) to obtain the title compound (394 mg) as a colorless powder. MS ESI posi: 259[M+H] + . Retention time: 1.012 min (method B)

[0815] Reference Example 1-6-2 below was synthesized using the method described in Reference Example 1-6-1 or an equivalent method, using the compound obtained in Reference Example 1-4-3, a commercially available compound, or a compound synthesized according to a method described in the literature or a similar method. The structure and LCMS data of the compound are shown in Table 7-1.

[0816] [Table 7-1] Reference example 1-7-1 1-(3-ethoxy-5-propylphenyl)ethane-1-one

[0817] [ka] This reaction was carried out based on the method described in the literature (The Journal of Organic Chemistry, Vol. 74, p. 3626, 2009). The compound obtained in Reference Example 1-5-8 (0.05 g), ethylboronic acid (22.8 mg), potassium carbonate (85.3 mg), palladium(II) acetate (9.23 mg), and 2-dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (RuPhos, 38.4 mg) were added to toluene (2.1 mL) and water (0.206 mL), and the mixture was stirred at 120°C for 70 minutes under microwave irradiation. Insoluble matter from the reaction mixture was filtered off, and the filtrate was concentrated. The obtained residue was purified by NH silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 80:20) to obtain the title compound (32.3 mg) as a colorless oily substance. MS ESI posi: 207[M+H] + . Retention time: 1.265 min (method B) Reference example 1-7-2 3-acetyl-5-ethoxybenzamide

[0818] [ka] To a solution of the compound obtained in Reference Example 1-5-6 (53.6 mg) in dimethyl sulfoxide (1 mL), 1 mol / L sodium hydroxide aqueous solution (2.83 mL), hydrogen peroxide (30% aqueous solution, 86.8 μL), and ethanol (1 mL) were added, and the mixture was stirred at room temperature for 4 hours. A saturated sodium thiosulfate aqueous solution-water mixture (1:1) was added to the reaction mixture, and it was extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 70:30 ~ ethyl acetate only) to obtain the title compound (66.1 mg) as a colorless solid. MS ESI posi: 208[M+H] + . Retention time: 0.741 min (method B) Reference example 1-7-3 3-acetyl-5-ethoxy-N-methylbenzamide

[0819] [ka] A solution of the compound obtained in Reference Example 1-5-9 (1.5 g) in tetrahydrofuran (23 mL) was cooled on ice, and methylamine (2 mol / L tetrahydrofuran solution, 25 mL), EDC (2.8 g), and HOBt (2.2 g) were added, and the mixture was stirred at room temperature for 17 hours. The reaction mixture was cooled on ice, saturated sodium bicarbonate aqueous solution and water were added, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The resulting residue was purified by preparative HPLC to obtain the title compound (35 mg) as a pale yellow oily substance. MS ESI / APCI Multi posi: 222[M+H] + . Retention time: 0.965 min (method F) Reference example 1-7-4 1,1'-(2-ethoxy-6-fluoro-1,4-phenylene)di(ethane-1-one)

[0820] [ka] (1) This reaction was carried out based on the method described in the literature (WO2014 / 191535). Potassium carbonate (3.38 g) and water (1.2 mL) were added to a solution of 4-bromo-2,6-difluorobenzaldehyde (3 g) in N,N-dimethylformamide (14 mL), and the mixture was stirred overnight at room temperature at 90 °C for 11 hours. Potassium carbonate (1.78 g) and iodoethane (3.91 mL) were added to the reaction mixture, and the mixture was stirred at 65 °C for 7 hours. The reaction mixture was filtered through Celite®, water was added to the filtrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed three times with 0.5 mol / L hydrochloric acid and once with saturated saline solution, filtered through a phase separator, and concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 80:20) to obtain 4-bromo-2-ethoxy-6-fluorobenzaldehyde (0.752 g) as a colorless solid. (2) Using the compound obtained in (1) above (0.2 g), the reaction was carried out in accordance with the method described in Reference Example 1-6-1(1) to obtain 1-(4-bromo-2-ethoxy-6-fluorophenyl)ethane-1-ol (218 mg) as a pale pink oily substance. (3) To a solution of the compound obtained in (2) above (218 mg) in n-hexane (10 mL), manganese dioxide (0.8 g) was added and the mixture was stirred overnight at room temperature. The reaction mixture was filtered through Celite® and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 70:30) to obtain 1-(4-bromo-2-ethoxy-6-fluorophenyl)ethane-1-one (81.3 mg) as a colorless oily substance. (4) To a mixed solution (1.56 mL-0.156 mL) of the compound obtained in (3) above (81.3 mg) with N,N-dimethylformamide and water, butyl vinyl ether (200 μL), palladium(II) acetate (2.10 mg), 1,3-bis(diphenylphosphino)propane (7.70 mg), and potassium carbonate (0.129 g) were added and the mixture was stirred at 120°C for 1 hour under microwave irradiation. Butyl vinyl ether (200 μL), palladium(II) acetate (6.99 mg), and 1,3-bis(diphenylphosphino)propane (25.7 mg) were added and the mixture was stirred at 120°C for 1 hour under microwave irradiation. 1 mol / L hydrochloric acid (3 mL) and ethyl acetate were added to the reaction mixture and stirred at room temperature for 1.5 hours. The reaction mixture was added to a 10% potassium carbonate aqueous solution and extracted with ethyl acetate. The organic layer was washed with saturated saline solution, filtered through a phase separator, and concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 70:30) to obtain the title compound (18.3 mg) as a pale yellow oily substance. MS ESI posi: 225[M+H] + . Retention time: 0.879 min (method B) Reference example 1-7-5 1-[3-ethoxy-5-fluoro-4-(1-hydroxyethyl)phenyl]ethane-1-one

[0821] [ka] Using the compound obtained in Reference Example 1-7-4(2) (95.3 mg), the reaction was carried out according to the method described in Reference Example 1-7-4(4), and the title compound (22.4 mg) was obtained as a colorless solid. MS ESI posi: 209[M-OH] + . Retention time: 0.773 min (method B) Reference example 1-7-6 4-Ethoxy-1-ethyl-1H-indazole-6-carbaldehyde

[0822] [ka] (1) To a solution of the compound (5.8 g) obtained in Reference Example 1-7-4(1) in N-methylpyrrolidone (8.7 mL), ethylhydrazine oxalate (3.9 g) was added and the mixture was stirred at room temperature for 24 hours. N-methylpyrrolidone (78 mL) was added to the reaction mixture and the mixture was stirred at 200 °C for 2.5 hours. n-hexane, ethyl acetate, water, and saturated brine were added to the reaction mixture and the mixture was partitioned into two layers. The aqueous layer was extracted with a mixed solvent of n-hexane and ethyl acetate. The organic layers were washed sequentially with water and saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5~60:40). n-hexane was added to the residue, and the insoluble matter was filtered off and the mixture was concentrated. The obtained residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate = 98:2 to 60:40) to obtain 6-bromo-4-ethoxy-1-ethylindazole (2.48 g) as a pale green oily substance. (2) Under a nitrogen atmosphere, the compound obtained in (1) above (2.48 g) and copper(I) cyanide (1.57 g) were mixed in a solution of N,N-dimethylacetamide (31 mL) and stirred at 150°C for 30 hours. After cooling to room temperature, 10% aqueous ammonia, saturated brine, and water were added to the reaction mixture, and it was extracted with ethyl acetate and concentrated. The resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate = 95:5 - ethyl acetate only). A mixed solvent of n-hexane and ethyl acetate was added to the resulting residue. The organic layer was sequentially washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated to obtain 4-ethoxy-1-ethylindazole-6-carbonitride (800 mg) as a pale yellow powder. (3) Under a nitrogen atmosphere, a toluene (36 mL) solution of the compound obtained in (2) above (1.54 g) was cooled to -40°C, and diisobutylaluminum hydride (1.0 mol / L toluene solution, 8.6 mL) was added and the mixture was stirred at the same temperature for 1 hour. Further diisobutylaluminum hydride (1.0 mol / L toluene solution, 3.0 mL) was added and the mixture was stirred at the same temperature for 10 minutes. Isopropyl alcohol (6 mL) was added dropwise to the reaction mixture, silica gel was added and the mixture was stirred for 5 minutes. The reaction mixture was returned to room temperature, filtered through Celite®, and the filtrate was concentrated to obtain the title compound (1.37 g) as a pale yellow oily substance. MS ESI / APCI Multi posi: 219 [M+H] + . Retention time: 0.980 min (method E) Reference example 1-7-7 1-[3,5-bis(cyclopropyloxy)-4-methylphenyl]ethane-1-one

[0823] [ka] (1) 700 mg of methyl 3,5-dihydroxy-4-methylbenzoate, 3.76 g of cesium carbonate, 32 mg of potassium iodide, and 1.86 g of cyclopropyl bromide were mixed with 15 mL of N-methylpyrrolidone and stirred at 200°C for 2 hours under microwave irradiation. Water was added to the reaction mixture, and it was extracted with a mixed solvent of n-hexane and ethyl acetate and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 98:2 to 80:20) to obtain a mixture containing methyl 3,5-bis(cyclopropoxy)-4-methylbenzoate (540 mg) as a colorless solid. (2) To a solution of the mixture obtained in (1) (540 mg) in tetrahydrofuran (21 mL), 1 mol / L aqueous sodium hydroxide solution (21 mL) and methanol (10 mL) were added and the mixture was stirred at room temperature for 5 days. The reaction mixture was concentrated and the aqueous layer was washed with n-hexane. 3 mol / L hydrochloric acid was added dropwise to the aqueous layer to adjust the pH to 5-6, and the insoluble material was filtered off. The obtained residue was purified by preparative HPLC to obtain 3,5-bis(cyclopropoxy)-4-methylbenzoic acid (75 mg) as a colorless powder. (3) A solution of the compound obtained in (2) above (72 mg) in tetrahydrofuran (1.5 mL) was cooled on ice, methyllithium (1 mol / L diethyl ether solution, 0.87 mL) was added dropwise, and the mixture was stirred at room temperature for 5 hours. The reaction mixture was cooled on ice, isopropyl alcohol was added dropwise, 1 mol / L hydrochloric acid was added to make it acidic, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate ~ 70:30) to obtain the title compound (92 mg) as a colorless oily substance. MS ESI posi: 247 [M+H] + . Retention time: 0.942 min (method A) Reference example 1-7-8 5-acetyl-3-ethoxy-1-ethylpyridine-2(1H)-one

[0824] [ka] (1) Under a nitrogen atmosphere, a solution of 5-bromopyridine-2,3-diol (2 g) in N,N-dimethylformamide (35 mL) was cooled on ice, sodium hydride (60% mineral oil dispersion, 1.0 g) was added, and the mixture was stirred at the same temperature for 45 minutes. Iodoethane (2.0 mL) was added dropwise, and the mixture was stirred at room temperature for 3 days. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 92:8~34:66) to obtain 5-bromo-3-ethoxy-1-ethylpyridine-2-one (2.31 g) as a pale yellow oily substance. (2) Using the compound obtained in (1) above (0.512 g), the reaction was carried out in accordance with the method described in Reference Example 1-7-6(2). However, N-methylpyrrolidone was used instead of N,N-dimethylacetamide, and the reaction was carried out at a temperature of 180°C. 5-Ethoxy-1-ethyl-6-oxopyridine-3-carbonitrile (0.3 g) was obtained as a colorless oily substance. (3) This reaction was carried out based on the method described in the literature (Journal of Medicinal Chemistry, Vol. 59, p. 1556, 2016). Under a nitrogen atmosphere, a solution of the compound obtained in (2) above (0.439 g) in diethyl ether (23 mL) was cooled on ice, and methylmagnesium bromide (3 mol / L diethyl ether solution, 1.5 mL) was added dropwise. The mixture was stirred at the same temperature for 3 hours, and then stirred for 12 hours while gradually returning to room temperature. Toluene (10 mL) was added to the reaction mixture, and the mixture was stirred at 65°C for 2 hours. The reaction mixture was cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 0.53 mL) was added, and the mixture was stirred at room temperature for 40 minutes and at 60°C for 50 minutes. The reaction mixture was cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 0.53 mL) was added, and the mixture was stirred at room temperature for 10 minutes and at 60°C for 80 minutes, and then returned to room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. 2 mol / L hydrochloric acid and 1 mol / L sodium hydroxide aqueous solution were added to the aqueous layer to adjust the pH to 6-7, and then extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 85:15 - ethyl acetate only) to obtain the title compound (0.069 g) as a colorless powder. MS ESI / APCI Multi posi: 210 [M+H] + . Retention time: 1.156 min (method F) Reference example 1-7-9 1-(4-ethoxy-1-ethyl-1H-benzimidazole-6-yl)ethane-1-one

[0825] [ka] (1) Potassium hydroxide (0.38 g) was added to a solution of 5-bromo-1,3-difluoro-2-nitrobenzene (1.5 g) in ethanol (20 mL) and stirred at room temperature for 2.5 days and then at 90°C for 45 minutes. The reaction mixture was concentrated, ethyl acetate was added, and the mixture was washed sequentially with water and saturated saline solution. The mixture was dried over anhydrous magnesium sulfate, the drying agent was filtered off, and the filtrate was concentrated to obtain 5-bromo-1-ethoxy-3-fluoro-2-nitrobenzene (1.63 g) as an orange oily substance. (2) A solution of the compound obtained in (1) above (1.63 g) in tetrahydrofuran (12 mL) was cooled on ice, 12 mol / L aqueous ethylamine solution (2.1 mL) was added, and the mixture was stirred at room temperature for 23 hours. The reaction mixture was concentrated, diethyl ether was added, and the mixture was washed sequentially with water and saturated saline solution. The mixture was dried over anhydrous magnesium sulfate, the drying agent was filtered off, and the filtrate was concentrated to obtain 5-bromo-3-ethoxy-N-ethyl-2-nitroaniline (1.79 g) as an orange powder. (3) Using the compound obtained in (2) above (1.62 g), the reaction was carried out in accordance with the method described in Reference Example 1-7-8(2) to obtain 3-ethoxy-5-(ethylamino)-4-nitrobenzonitrile (1.0 g) as a red powder. (4) The mixture of the compound obtained in (3) above (0.5 g), iron powder (0.593 g), saturated ammonium chloride aqueous solution (5 mL), and ethanol (16 mL) was stirred at room temperature for 11 hours, and then stirred at 65°C for 80 minutes. 1 mol / L sodium hydroxide aqueous solution was added to the reaction mixture to adjust the pH to 9-10, and the mixture was filtered through Celite® and the filtrate was concentrated. Water and ethyl acetate were added to the residue to separate it into two layers. 1 mol / L sodium hydroxide aqueous solution was added to the aqueous layer to adjust the pH to 9-10, and the mixture was extracted with ethyl acetate. The organic layers were washed together with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 50:50) to obtain 4-amino-3-ethoxy-5-(ethoxyamino)benzonitrile (222 mg) as a beige powder. (5) To a solution of the compound obtained in (4) above (0.1 g) and triethyl orthoformate (2.4 mL), p-toluenesulfonic acid monohydrate (9 mg) was added and the mixture was stirred at room temperature for 17 hours. The reaction solution was diluted with ethyl acetate and washed with saturated sodium bicarbonate aqueous solution. The aqueous layer was extracted with ethyl acetate and concentrated. The resulting residue was purified by preparative HPLC to obtain 7-ethoxy-3-ethylbenzimidazole-5-carbonitride (82 mg) as a colorless gum-like substance. (6) A solution of the compound obtained in (5) (82 mg) in diethyl ether (3.8 mL) was cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 0.254 mL) was added dropwise, and the mixture was stirred at the same temperature for 25 minutes and at room temperature for 20 hours. Tetrahydrofuran (3.8 mL) was added to the reaction mixture and cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 0.254 mL) was added, and the mixture was stirred at the same temperature for 30 minutes and at room temperature for 90 minutes. The reaction mixture was cooled on ice, methylmagnesium bromide (3 mol / L diethyl ether solution, 1 mL) was added, and the mixture was stirred at room temperature for 1 hour. This procedure was repeated twice. Water was added to the reaction mixture and it was concentrated. The resulting residue was purified by preparative HPLC to obtain the title compound (35 mg) as a colorless solid. MS ESI posi: 233 [M+H] + . Retention time: 0.752 min (method C) Reference example 1-8-1 4-acetyl-2,6-diethoxybenzonitrile

[0826] [ka] To a solution of the compound obtained in Reference Example 1-5-1 (232 mg) in N,N-dimethylacetamide (3.2 mL), copper(I) cyanide (217 mg) was added and the mixture was stirred at 150°C for 1 hour under microwave irradiation. Ethyl acetate was added to the reaction mixture, and this was then added to a 10% aqueous ammonium solution and extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered using a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 50:50) to obtain the title compound (31.7 mg) as a colorless solid. MS ESI posi: 234[M+H] + . Retention time: 1.004 min (method B) Reference example 1-8-2 1-(4-cyclopropyl-3,5-diethoxyphenyl)ethane-1-one

[0827] [ka] Using the compound obtained in Reference Example 1-5-1 (50 mg) and cyclopropylboronic acid (22.4 mg), the reaction was carried out according to the method described in Reference Example 1-7-1 to obtain the title compound (34 mg) as a colorless solid. MS ESI posi: 249[M+H] + . Retention time: 1.199 min (method B)

[0828] Reference Examples 1-8-3 to 1-8-4 below were synthesized using the method described in Reference Example 1-8-2 or an equivalent method, using compounds obtained in Reference Example 1-5-1, commercially available compounds, or compounds synthesized according to methods described in the literature or similar methods. The structures and LCMS data of the compounds are shown in Table 8-1.

[0829] [Table 8-1] Reference example 1-8-5 1,1'-(2,6-diethoxy-1,4-phenylene)di(ethane-1-one)

[0830] [ka] This reaction was carried out based on the method described in the literature (The Journal of Organic Chemistry, Vol. 66, p. 4340, 2001). Under a nitrogen atmosphere, butyl vinyl ether (1.12 mL), palladium(II) acetate (11.7 mg), 1,3-bis(diphenylphosphin)propane (43.1 mg), potassium carbonate (722 mg), and water (0.87 mL) were added to a solution of the compound obtained in Reference Example 1-5-1 (0.5 g) in N,N-dimethylformamide (8.7 mL), and the mixture was stirred at 120 °C for 1 hour under microwave irradiation. 1 mol / L hydrochloric acid (10 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 3 hours. 10% potassium carbonate aqueous solution (50 mL) was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered off the drying agent, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 60:40) to obtain the title compound (407 mg) as a colorless solid. MS ESI posi: 251[M+H] + . Retention time: 0.994 min (method B) Reference example 1-8-6 1-[3,5-diethoxy-4-(propan-2-yl)phenyl]ethane-1-one

[0831] [ka] To a methanol (3 mL) solution of the compound obtained in Reference Example 1-8-3 (37 mg), palladium-carbon (19 mg) was added and the mixture was stirred at room temperature under a hydrogen atmosphere for 3 hours. Insoluble matter was filtered off, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 75:25) to obtain the title compound (29 mg) as a colorless solid. MS ESI posi: 251[M+H] + . Retention time: 1.338 min (method B)

[0832] Reference Example 1-8-7 below was synthesized using cyclopropylboronic acid, the compound obtained in Reference Example 1-14-6, by the method described in Reference Example 1-8-2 or a similar method. The structure and LCMS data of the compound are shown in Table 8-2.

[0833] [Table 8-2] Reference example 1-9-1 1-[3,5-diethoxy-4-(1-hydroxycyclopropyl)phenyl]ethane-1-one

[0834] [ka] (1) To a solution of the compound obtained in Reference Example 1-5-1 (0.604 g) in toluene (21 mL), ethylene glycol (8.42 mL) and p-toluenesulfonic acid monohydrate (40.0 mg) were added, and the mixture was stirred under reflux for 3 hours. The reaction mixture was cooled on ice, saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 95:5~90:10) to obtain 2-(4-bromo-3,5-diethoxyphenyl)-2-methyl-1,3-dioxolane (0.633 g) as a colorless solid. (2) This reaction was carried out in reference to the method described in the literature (WO2015 / 159233). Under a nitrogen atmosphere, a suspension of magnesium (66 mg) and iodine (14 mg) in diethyl ether (3.6 mL) was mixed with the compound obtained in (1) above (900 mg) in a 1:1 ratio (1.8 mL) of diethyl ether-tetrahydrofuran, and tetrahydrofuran (3.6 mL) was added. The temperature was gradually increased and the mixture was stirred under reflux for 5 hours. The reaction mixture was cooled on ice, and a solution of 1,3-dichloroacetone (345 mg) in tetrahydrofuran (3.6 mL) was added. The mixture was stirred at room temperature for 80 minutes. The reaction mixture was cooled on ice, and a solution of iron(III) chloride (9 mg) in tetrahydrofuran (1.8 mL) and ethylmagnesium bromide (3 mol / L diethyl ether solution, 4.5 mL) were added over 5 minutes. The mixture was stirred at room temperature for 12 hours. The reaction mixture was cooled on ice, 18 mL of saturated ammonium chloride aqueous solution was added, 1 mol / L hydrochloric acid was added to adjust the acidity, and ethyl acetate was added to partition the mixture into two layers. The aqueous layer was extracted with ethyl acetate, and the organic layers were combined and washed with saturated brine. The mixture was dried over anhydrous magnesium sulfate, the drying agent was filtered off, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 94:6 to 60:40) to obtain 1-[2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]cyclopropan-1-ol (220 mg) as a pale yellow solid. (3) A solution of the compound obtained in (2) above (0.11 g) in tetrahydrofuran (2.5 mL) was cooled on ice, 1 mol / L hydrochloric acid (2.5 mL) was added, and the mixture was stirred at room temperature for 30 minutes. Water was added to the reaction mixture and extracted with ethyl acetate. The mixture was filtered through a phase separator and concentrated to obtain the title compound (0.088 g) as a pale yellow oily substance. MS ESI posi: 247[M-OH] + . Retention time: 0.742 min (method A) Reference example 1-9-2 1-[3,5-diethoxy-4-(methanesulfinyl)phenyl]ethane-1-one

[0835] [ka] (1) This reaction was carried out based on the method described in the literature (Journal of Medicinal Chemistry, Vol. 59, p. 6772, 2016). Under a nitrogen atmosphere, a mixed solution (2 mL-1 mL) of the compound obtained in Reference Example 1-9-1(1) with diethyl ether-tetrahydrofuran was cooled to -78°C, and n-butyllithium (1.60 mol / L n-hexane solution, 0.38 mL) was added. The reaction mixture was stirred under ice for 30 minutes, cooled to -78°C, dimethyl disulfide (68.0 μL) was added, and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was cooled on ice, saturated ammonium chloride aqueous solution was added, and diethyl ether extraction was performed. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 80:20) to obtain 2-[3,5-diethoxy-4-(methylsulfanyl)phenyl]-2-methyl-1,3-dioxolane (75.8 mg) as a colorless solid. (2) Under a nitrogen atmosphere, a methanol (1.4 mL) solution of the compound obtained in (1) above (40.8 mg) was cooled on ice, and a water (1.4 mL) solution of sodium periodate (29.2 mg) was added. The mixture was stirred at the same temperature for 1 hour, and then stirred at room temperature for 7 hours. Saturated saline solution was added to the reaction mixture, extracted with chloroform, filtered through a phase separator, and concentrated. The resulting residue was purified by NH silica gel column chromatography (n-hexane:ethyl acetate = 70:30 - ethyl acetate only) to obtain 2-[3,5-diethoxy-4-(methanesulfinyl)phenyl]-2-methyl-1,3-dioxolane (33.8 mg) as a colorless solid. (3) Using the compound obtained in (2) above (33.8 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3) to obtain the title compound (34.0 mg) as a colorless solid. MS ESI posi: 271[M+H] + . Retention time: 0.636 min (method B) Reference example 1-9-3 1-[3,5-diethoxy-4-(methanesulfonyl)phenyl]ethane-1-one

[0836] [ka] (1) A chloroform solution (1.2 mL) of the compound obtained in Reference Example 1-9-2(1) (35 mg) was cooled on ice, methachloroperbenzoic acid (64.8 mg) was added, and the mixture was stirred at the same temperature for 10 minutes and at room temperature for 20 minutes. The reaction mixture was cooled on ice, saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted three times with chloroform. The organic layer was washed with saturated sodium thiosulfate aqueous solution, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ ethyl acetate only) to obtain 2-[3,5-diethoxy-4-(methanesulfonyl)phenyl]-2-methyl-1,3-dioxolane (37.6 mg) as a colorless solid. (2) Using the compound obtained in (1) above (37.6 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3) to obtain the title compound (35.6 mg) as a colorless solid. MS ESI posi: 287[M+H] + . Retention time: 0.696 min (method B) Reference example 1-10-1 1-[2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]ethane-1-ol

[0837] [ka] (1) Under a nitrogen atmosphere, a mixed solution (20 mL-10 mL) of the compound (1 g) obtained in Reference Example 1-9-1(1) with diethyl ether-tetrahydrofuran was cooled to -78°C, and n-butyllithium (1.60 mol / L n-hexane solution, 2.5 mL) was added and the mixture was stirred on ice for 30 minutes. The mixture was cooled to -78°C, N,N-dimethylformamide (0.35 mL) was added and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was returned to ice and saturated ammonium chloride aqueous solution (30 mL) was added and extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 75:25) to obtain 2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)benzaldehyde (0.602 g) as a colorless solid. (2) Using the compound obtained in (1) above (0.1 g), the reaction was carried out in accordance with the method described in Reference Example 1-6-1(1) to obtain 1-[2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]ethane-1-ol (83.3 mg) as a colorless solid. (3) Using the compound obtained in (2) above (83.3 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3) to obtain the title compound (68.0 mg) as a colorless solid. MS ESI posi: 235[M-OH] + . Retention time: 0.965 min (method B) Reference example 1-10-2 1-[4-(difluoromethyl)-3,5-diethoxyphenyl]ethane-1-one

[0838] [ka] (1) To a solution of the compound obtained in Reference Example 1-10-1(1) (0.07 g) in chloroform (1.7 mL), bis(2-methoxyethyl)aminosulfate trifluoride (138 μL) was added and the mixture was stirred at room temperature for 1 hour. Another bis(2-methoxyethyl)aminosulfate trifluoride (138 μL) was added and the mixture was stirred overnight at room temperature at 60°C for 10 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture, extracted with chloroform, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 50:50) to obtain 2-[4-(difluoromethyl)-3,5-diethoxyphenyl]-2-methyl-1,3-dioxolane (31.3 mg) as a pale yellow solid. (2) Using the compound obtained in (1) above (31.3 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3) to obtain the title compound (60.6 mg) as a colorless solid. MS ESI posi: 259[M+H] + . Retention time: 1.115 min (method B) Reference example 1-10-3 (4-acetyl-2,6-diethoxyphenyl)methyl acetate

[0839] [ka] (1) A methanol (2 mL) solution of the compound (50.0 mg) obtained in Reference Example 1-10-1(1) was cooled on ice, and sodium borohydride (10.1 mg) was added. The mixture was stirred at the same temperature for 40 minutes. After cooling on ice, saturated ammonium chloride aqueous solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 60:40) to obtain [2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]methanol (43.4 mg) as a colorless solid. (2) To a chloroform (1.5 mL) solution of the compound obtained in (1) above (43.4 mg), triethylamine (64.3 μL) and acetyl chloride (66.0 μL) were added and the mixture was stirred at room temperature for 4 hours. The reaction mixture was cooled on ice, saturated sodium bicarbonate aqueous solution was added, and the mixture was extracted with chloroform, filtered through a phase separator, and concentrated to obtain [2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]methyl acetate (59.7 mg) as a pale yellow oily substance. (3) Using the compound obtained in (2) above (59.7 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3) to obtain the title compound (30.7 mg) as a colorless solid. MS ESI posi: 303[M+Na] + . Retention time: 0.975 min (method B) Reference example 1-10-4 1-[3,5-diethoxy-4-(2,2,2-trifluoro-1-hydroxyethyl)phenyl]ethane-1-one

[0840] [ka] (1) This reaction was carried out in reference to the method described in the literature (Journal of the American Chemical Society, Vol. 111, p. 393, 1989). Under a nitrogen atmosphere, a solution of the compound obtained in Reference Example 1-10-1(1) (70 mg) in tetrahydrofuran (2.5 mL) was cooled on ice, (trifluoromethyl)trimethylsilane (55.4 μL) and tetrabutylammonium fluoride (1 mol / L tetrahydrofuran solution, 25.0 μL) were added, and the mixture was stirred at room temperature for 1.5 hours. Then, 1 mol / L hydrochloric acid (1 mL) was added, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The organic layer was washed with saturated brine, filtered through a phase separator, and concentrated. The obtained residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 50:50) to obtain 1-[2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]-2,2,2-trifluoroethane-1-ol (42 mg) as a colorless oily substance. (2) Using the compound obtained in (1) above (90 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3), and the title compound (61 mg) was obtained as a colorless solid. MS ESI posi: 307[M+H] + . Retention time: 1.053 min (method B) Reference example 1-10-5 1-(4-acetyl-2,6-diethoxyphenyl)-2,2,2-trifluoroethane-1-one

[0841] [ka] (1) A solution of the compound obtained in Reference Example 1-10-4(1) (42 mg) in n-hexane (3 mL) was mixed with manganese dioxide (0.8 g) and stirred at room temperature for 3.5 hours and at 60°C for 2 hours. The reaction mixture was filtered through Celite® and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 50:50) to obtain 1-[2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)phenyl]-2,2,2-trifluoroethane-1-one (31 mg) as a colorless solid. (2) Using the compound obtained in (1) above (31 mg), the reaction was carried out in accordance with the method described in Reference Example 1-9-1(3), and the title compound (34 mg) was obtained as a colorless solid. MS ESI posi: 305[M+H] + . Retention time: 1.145 min (method B) Reference example 1-10-6 Methyl 4-acetyl-2,6-diethoxybenzoate

[0842] [ka] (1) To a solution of the compound obtained in Reference Example 1-10-1(1) (266 mg) in 2-methyl-2-butene (0.81 mL), sodium dihydrogen phosphate (456 mg), tert-butyl alcohol (3.8 mL), water (1.3 mL), and tetrahydrofuran (3.8 mL) were added, the mixture was cooled on ice, sodium chlorite (344 mg) was slowly added, and the mixture was stirred at room temperature for 1.5 hours. The reaction mixture was cooled on ice, water (50 mL) and citric acid (1 g) were added to make it acidic (pH 1-2), and the mixture was extracted twice with ethyl acetate. The organic layer was extracted twice with saturated sodium bicarbonate aqueous solution (30 mL), citric acid (4 g) was added to the aqueous layer to make it acidic (pH 5), and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated saline solution, filtered through a phase separator, and concentrated to obtain 2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)benzoic acid (205 mg) as a colorless solid. (2) Under a nitrogen atmosphere, a chloroform-methanol mixed solution (2 mL - 1 mL) of the compound obtained in (1) (32 mg) was cooled on ice, and trimethylsilyldiazomethane (2 mol / L diethyl ether solution, 162 μL) was added and the mixture was stirred at room temperature for 2 hours. The reaction mixture was cooled on ice, water was added and extracted with chloroform, filtered with a phase separator and concentrated. The resulting residue was purified by silica gel column chromatography (n-hexane only ~ n-hexane:ethyl acetate = 50:50) to obtain methyl 2,6-diethoxy-4-(2-methyl-1,3-dioxolan-2-yl)benzoate (28.6 mg) as a colorless solid. (3) To a mixed solution (920 μL-920 μL) of the compound obtained in (2) above (28.6 mg) with acetone and water, p-toluenesulfonic acid monohydrate (17.5 mg) was added and the mixture was stirred for 2.5 hours. Another 17.5 mg of p-toluenesulfonic acid monohydrate was added and the mixture was stirred overnight at room temperature. Saturated sodium bicarbonate aqueou...

Claims

1. The following formula [I] 【Chemistry 1】 {In the above formula [I], X is carboxy, C １－４ A group selected from the following formula group [II]: alkoxycarbonyl, carbamoyl, tetrazolyl, or 【Chemistry 2】 Show; W is a linear C １－３ Alkanedyl or a structure selected from the following group of formulas [III] 【Transformation 3】 Show, Here, The linear C １－３ alkanediyl is C １－６ alkyl (the C １－６ alkyl may be substituted with one group selected from the group consisting of hydroxy and carboxy), halo C １－６ alkyl, C ３－８ cycloalkyl, phenyl C １－３ alkyl, and pyridyl C １－３ alkyl may be substituted with one group selected from the group consisting of, And the linear C １－３ If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A １ , ring A ２ , and ring A ３ C ３－８ This represents a cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, or a 4-8 membered saturated heterocycle containing a nitrogen atom. Here, The sulfur atom in the 4-8 member saturated heterocycle containing the sulfur atom may be substituted with 1-2 oxos. The nitrogen atom in the saturated heterocycle of 4 to 8 members containing the nitrogen atom is C １－４ Alkylcarbonyl and C １－４ It may be substituted with one group selected from the group consisting of alkoxycarbonyls. Also, R Ａ１１ , R Ａ２１ , and R Ａ３１ These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkyl carbonyl, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C １－３ It may be substituted with alkyl. R Ａ１２ , R Ａ２２ , and R Ａ３２ These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ These may each combine to form an oxo, moreover, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ Each of these atoms combines with the carbon atoms in the adjacent ring to form C ３－６ They may also form cycloalkanes; R １ This represents a hydrogen atom or a methyl atom; R ２ C ６－１０ Alkyl, C ６－１０ Alkenil, C ６－１０ Alkynyl, or a group represented by the following formula [IV-1] or [IV-2] 【Chemistry 4】 Show, Here, Ring B １ C ３－８ This represents a cycloalkyl, a saturated 4-8 member heterocycline containing a nitrogen atom, a phenyl, or a 5-6 member heteroaryl containing a nitrogen atom. R Ｂ１１ and R Ｂ１２ These are, independently, hydrogen atoms, halogen atoms, and C １－６ Alkyl, or C １－６ It shows alkoxy, L １ C ３－８ Alkanedil (the C ３－８ The alkanediyl may be substituted with 1 to 5 fluorine atoms. (Formula [V-6]: -CH ２ CH ２ CH = C(CH ３ A structure represented by ) or a structure represented by the following formula [V-1] 【Transformation 5】 Show, Here, n11 represents an integer between 0 and 3. n12 represents an integer from 0 to 5. n13 represents an integer between 0 and 3. Also, C ３－８ R is one of the carbon atoms in alkanediyl. ２ The atom that is two or more atoms away from the nitrogen atom to which it is bonded is of the formula -O-, formula -S-, or formula -N(R Ｌ１１ ) - can be replaced with, moreover, C ３－８ R is one of the two consecutive carbon atoms in an alkanediyl. ２ The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined as -C(=O)N(R) Ｌ１２ ) - can be replaced with, R Ｌ１１ is a hydrogen atom or C １－３ It indicates alkyl, R Ｌ１２ is a hydrogen atom or C １－３ It indicates alkyl, Ring B ２ This represents a partially saturated 9-10 membered fused aryl ring, or a 9-10 membered fused heteroaryl ring containing a nitrogen atom. R Ｂ２１ and R Ｂ２２ These are, independently, hydrogen atoms, halogen atoms, and C １－６ Alkyl, or C １－６ It shows alkoxy, L ２ C １－２ Alkanedil (the C １－２ The alkanediyl may be substituted with 1 to 4 fluorine atoms. ３－６ Alkanedil (the C ３－６ The alkanediyl may be substituted with 1 to 5 fluorine atoms, or the structure represented by the following formula [V-2] 【Transformation 6】 Show, Here, n21 represents an integer between 0 and 3. n22 represents an integer from 0 to 5. n23 represents an integer between 0 and 3. Also, C ３－６ R is one of the carbon atoms in alkanediyl. ２ The atom that is two or more atoms away from the nitrogen atom to which it is bonded is of the formula -O-, formula -S-, or formula -N(R Ｌ２１ ) - can be replaced with, moreover, C ３－６ R is one of the two consecutive carbon atoms in an alkanediyl. ２ The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined as -C(=O)N(R) Ｌ２２ ) - can be replaced with, R Ｌ２１ is a hydrogen atom or C １－３ It indicates alkyl, R Ｌ２２ is a hydrogen atom or C １－３ It indicates alkyl; R ３ is a hydrogen atom or C １－３ Alkyl (the C １－３ The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. R ４ is a group represented by the following formula [VI] 【Transformation 7】 Show, Here, Ring C represents a phenyl, a 6-membered heteroaryl containing a nitrogen atom, or a 9- to 10-membered fused heteroaryl. The phenyl contains a halogen atom, C １－６ Alkyl, C １－６ Alkoxy and C １－６ It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C １－６ alkyl (the C １－６ alkyl may be substituted with one group selected from the group consisting of hydroxy and C １－６ alkoxy).), halo C １－６ alkyl (the halo C １－６ alkyl may be substituted with one hydroxy).), C ２－６ alkenyl, C ２－６ alkynyl, C ３－８ cycloalkyl (the C ３－８ cycloalkyl may be substituted with one hydroxy).), C １－６ alkoxy, halo C １－６ alkoxy, C ３－８ cycloalkoxy, C １－６ alkylsulfanyl, C １－６ alkylsulfinyl, C １－６ alkylsulfonyl, mono C １－６ alkylamino, di C １－６ alkylamino, C １－６ alkylcarbonyl, halo C １－６ alkylcarbonyl, C １－６ alkoxycarbonyl, mono C １－６ alkylaminocarbonyl, and di C １－６ alkylaminocarbonyl may be substituted with 1 to 4 groups selected identically or differently from the group consisting of: The six-membered heteroaryl containing the nitrogen atom has one C １－６ Substituted with alkoxy, and further, Cyano, C １－６ Alkyl, C １－６ They may be substituted with one or two groups selected identically or differently from the group consisting of alkoxys and oxos. The 9-10 member fused ring heteroaryl is C １－６ Alkyl, C １－６ They may be substituted with one to four groups selected identically or differently from the group consisting of alkoxys and oxos; Also, R ３ and R ４ These may combine with adjacent carbon atoms to form a partially saturated 9-10 membered fused hydrocarbon aromatic ring or a partially saturated 9-10 membered fused heteroaromatic ring containing an oxygen atom. Here, The partially saturated 9-10 membered fused hydrocarbon aromatic ring may be substituted with 1-2 halogen atoms. The 9-10 membered heteroaromatic ring containing the partially saturated oxygen atom may be substituted with 1-2 halogen atoms. A pharmaceutical product containing a compound represented by [the specified formula], a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

2. In the group of equations relating W [III], R Ａ１１ , R Ａ２１ , and R Ａ３１ These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C １－６ Alkyl, C １－６ Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C １－３ It may be substituted with alkyl. R Ａ１２ , R Ａ２２ , and R Ａ３２ These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ These may each combine to form an oxo, moreover, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ Each of these atoms combines with the carbon atoms in the adjacent ring to form C ３－６ They may form cycloalkanes, R ２ In equation [IV-1] relating to, L １ C ３－８ Alkanedil (the C ３－８ The alkanediyl may be substituted with 1 to 5 fluorine atoms, or it may have a structure represented by formula [V-1], Here, C ３－８ R is one of the carbon atoms in alkanediyl. ２ The atom that is two or more atoms away from the nitrogen atom to which it is bonded is of the formula -O-, formula -S-, or formula -N(R Ｌ１１ ) - can be replaced with, moreover, C ３－８ R is one of the two consecutive carbon atoms in an alkanediyl. ２ The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined as -C(=O)N(R) Ｌ１２ ) - can be replaced with, R Ｌ１１ is a hydrogen atom or C １－３ It indicates alkyl, R Ｌ１２ is a hydrogen atom or C １－３ A pharmaceutical product containing, as an active ingredient, the compound described in claim 1, or a pharmaceutically acceptable salt thereof, or a hydrate thereof, which exhibits alkylity.

3. In the above formula [I], W is a linear C １－３ Alkanedyl or a structure selected from the following group of formulas [III] 【Transformation 8】 And, Here, The linear C １－３ Alkandiyl is C １－６ Alkyl (the C １－６ The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl groups. １－６ Alkyl, C ３－８ Cycloalkyl, phenyl C １－３ Alkyl and pyridyl C １－３ It may be substituted with one group selected from the group consisting of alkyl groups. And the linear C １－３ If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A １ C ３－８ Cycloalkane, dihydroindene, oxetane, tetrahydrofuran, tetrahydropyran, tetrahydrothiopyran, azetidine, pyrrolidine, or piperidine. Ring A ２ C ３－８ It is a cycloalkane or tetrahydropyran, Ring A ３ C ３－８ These are cycloalkanes, dihydroindenes, or tetrahydropyrans. Here, The sulfur atom in the tetrahydrothiopyran may be substituted with one or two oxos. Also, Each nitrogen atom in azetidine, pyrrolidine, and piperidine is one carbon atom. １－４ It may be substituted with an alkylcarbonyl, and, R Ａ１１ C is a hydrogen atom, hydroxyl, carboxyl, halogen atom, C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkyl carbonyl, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C １－３ It may be substituted with alkyl. R Ａ１２ This represents a hydrogen atom, a halogen atom, or a methyl atom. Also, R Ａ１１ and R Ａ１２ These may each combine to form an oxo, R Ａ２１ and R Ａ２２ Both are hydrogen atoms, R Ａ３１ and R Ａ３２ Both are hydrogen atoms, Furthermore, R Ａ１１ and R Ａ１２ Each of these atoms combines with the carbon atoms in the adjacent ring to form C ３－６ They may also form cycloalkanes; R ２ However, C ６－１０ Alkyl groups, or groups represented by the following formulas [IV-1] or [IV-2] 【Chemistry 9】 And, Here, Ring B １ C ３－８ It is a cycloalkyl, piperidinyl, phenyl, pyrazolyl, or pyridyl, R Ｂ１１ and R Ｂ１２ These are, independently, hydrogen atoms, halogen atoms, and C １－６ Alkyl, or C １－６ It is an alkoxy, L １ The structure is represented by the following formulas [V-3] to [V-12] and [V-14] to [V-19]. 【Chemistry 10】 It is one of the following: Here, n4 represents an integer between 3 and 5. n12' represents an integer between 0 and 3. n12" represents an integer from 0 to 3. Also, Ring B ２ These are dihydroindenyl, indolyl, or isoindlinyl, R Ｂ２１ and R Ｂ２２ They are identically hydrogen atoms, L ２ The structure is represented by the following formula [V-20]. 【Chemistry 11】 And, Here, n5 represents an integer between 1 and 2; R ４ However, the base represented by the following formula [VI] 【Chemistry 12】 And, Here, Ring C is phenyl, pyridyl, pyrimidinyl, dihydropyridinyl, dihydrobenzofuranyl, benzodioxanyl, indolyl, indazolyl, benzimidazolyl, pyrazolopyridinyl, indolinyl, or dihydroquinazolinyl. The phenyl contains a halogen atom, C １－６ Alkyl, C １－６ Alkoxy and C １－６ It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C １－６ Alkyl (the C １－６ Alkyl is hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C １－６ Alkyl (the halo C １－６ The alkyl group may be substituted with one hydroxyl group. ２－６ Alkenil, C ３－８ Cycloalkyl (the C ３－８ The cycloalkyl group may be substituted with one hydroxyl group. １－６ Alkoxy, Halo C １－６ Alkoxy, C ３－８ Cycloalkoxy, C １－６ Alkyl sulfinyl, C １－６ Alkyl sulfonyl, mono C １－６ Alkylamino, diC １－６ Alkylamino, C １－６ Alkylcarbonyl, Halo C １－６ Alkylcarbonyl, C １－６ Alkoxycarbonyl and mono-C １－６ They may be substituted with one to four groups selected identically or differently from the group consisting of alkylaminocarbonyl groups. The pyridyl contains one C １－６ Substituted with alkoxy, and further, Cyano and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. The pyrimidinyl has one C １－６ Substituted with alkoxy, and further, 1 C １－６ It may be substituted with alkoxy, The dihydropyridinyl contains one C １－６ Substituted with alkoxy, and further, C １－６ They may be substituted with one or two groups selected identically or differently from the group consisting of alkyl and oxo. The dihydrobenzofuranyl and benzodioxanyl contain one C １ - ６ It may be substituted with alkoxy, The indolyl, indazolyl, benzimidazolyl, pyrazolopyridinyl, and indolinyl are C １－６ Alkyl and C １－６ They may be substituted with one or two groups selected identically or differently from the group consisting of alkoxys. The dihydroquinazolinyl is C １－６ Alkyl, C １－６ They may be substituted with one to four groups selected identically or differently from the group consisting of alkoxys and oxos; Also, R ３ and R ４ However, the fused rings formed when they combine with adjacent carbon atoms are dihydroindene or dihydrobenzofuran. The dihydroindene and dihydrobenzofuran may be substituted with one or two halogens. A pharmaceutical product containing the compound described in claim 1 or 2, a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

4. In the above formula [I], X is carboxy, C １－４ It is an alkoxycarbonyl or tetrazolyl; R １ However, it is a hydrogen atom; R ２ However, the base represented by the aforementioned formula [IV-1] or [IV-2] 【Chemistry 13】 A pharmaceutical product comprising the compound described in claim 1 or 2, a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

5. In the above formula [I], W is methanediyl or a structure represented by the following formula [III-1] 【Chemistry 14】 And, Here, The methanediyl is C １－６ Alkyl (the C １－６ The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl groups. １－６ Alkyl, C ３－８ Cycloalkyl, phenyl C １－３ Alkyl and pyridyl C １－３ It may be substituted with one group selected from the group consisting of alkyl groups. Furthermore, if the methanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Also, In the structure represented by formula [III-1], Ring A １ C ３－８ A cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, or a 4-8 membered saturated heterocycle containing a nitrogen atom. Here, The sulfur atom in the 4-8 member saturated heterocycle containing the sulfur atom may be substituted with 1-2 oxos. Also, The nitrogen atom in the saturated heterocycle of 4 to 8 members containing the nitrogen atom is C １－４ Alkylcarbonyl and C １－４ It may be substituted with one group selected from the group consisting of alkoxycarbonyls. and, R Ａ１１ C is a hydrogen atom, hydroxyl, carboxyl, halogen atom, C １－６ Alkyl, C １－６ Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C １－３ It may be substituted with alkyl. R Ａ１２ is a hydrogen atom, a halogen atom, or a methyl atom, Also, R Ａ１１ and R Ａ１２ These may each combine to form an oxo, moreover, R Ａ１１ and R Ａ１２ Each of these atoms combines with the carbon atoms in the adjacent ring to form C ３－６ They may form cycloalkanes. A pharmaceutical product containing the compound described in claim 1, 2, or 4, or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient.

6. In the above formula [I], R ４ However, the base represented by the following formula [VI] 【Chemistry 15】 And, Here, The carbon ring is phenyl, The phenyl contains a halogen atom, C １－６ Alkyl, C １－６ Alkoxy and C １－６ It is substituted with one group selected from the group consisting of alkylcarbonyls, and further, Hydroxy, carboxy, carbamoyl, cyano, halogen atom, C １－６ Alkyl (the C １－６ Alkyl is hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C １－６ Alkyl (the halo C １－６ The alkyl group may be substituted with one hydroxyl group. ２－６ Alkenil, C ２－６ Alkinyl, C ３－８ Cycloalkyl (the C ３－８ The cycloalkyl group may be substituted with one hydroxyl group. １－６ Alkoxy, Halo C １－６ Alkoxy, C ３－８ Cycloalkoxy, C １－６ Alkyl sulfanyl, C １－６ Alkyl sulfinyl, C １－６ Alkyl sulfonyl, mono C １－６ Alkylamino, diC １－６ Alkylamino, C １－６ Alkylcarbonyl, Halo C １－６ Alkylcarbonyl, C １－６ Alkoxycarbonyl, monoC １－６ Alkylaminocarbonyl and diC １－６ They may be substituted with one to four groups selected identically or differently from the group consisting of alkylaminocarbonyl groups. A pharmaceutical product containing a compound according to any one of claims 1, 2, 4, or 5, or a pharmaceutically acceptable salt thereof, or a hydrate thereof, as an active ingredient.

7. In the above formula [I], R ２ However, the base represented by the following formula [IV-1] or [IV-2] 【Chemistry 16】 And, Here, Ring B １ It is phenyl, R Ｂ１１ and R Ｂ１２ These are, independently, hydrogen atoms, halogen atoms, and C １－６ Alkyl, or C １－６ It is an alkoxy, L １ However, the structure is represented by the following formulas [V-3] to [V-5], [V-7] to [V-8], [V-11] to [V-12], [V-14] to [V-16] 【Chemistry 17】 It is one of the following: Here, n4 represents an integer between 3 and 5. Ring B ２ These are dihydroindenyl, indolyl, or isoindlinyl, R Ｂ２１ and R Ｂ２２ They are identically hydrogen atoms, L ２ The structure is represented by the following formula [V-20]. [Chemistry 18] And, Here, n5 is an integer between 1 and 2. A pharmaceutical product containing, as an active ingredient, a compound according to any one of claims 1, 2, 4 to 6, or a pharmaceutically acceptable salt thereof, or a hydrate thereof.

8. In the above formula [I], X is a carboxyl; W is a structure represented by the following formulas [III-4] to [III-17]. 【Chemistry 19】 It is either one of the following; R ２ However, the base represented by the following formula [IV-1] or [IV-2] 【Chemistry 20】 And, Here, Ring B １ It is phenyl, R Ｂ１１ and R Ｂ１２ The same is true for hydrogen atoms And, L １ However, the structure is represented by the following formulas [V-3], [V-8], [V-12], [V-14], or [V-15]. 【Chemistry 21】 And, Here, n4 is an integer between 3 and 4, Also, Ring B ２ It is dihydroindenyl, R Ｂ２１ and R Ｂ２２ They are identically hydrogen atoms, L ２ The structure is represented by the following formula [V-20]. 【Chemistry 22】 And, Here, n5 is 2; R ３ However, the stereochemical configuration is represented by the following equation [VII] 【Chemistry 23】 It is a methyl having; R ４ However, the base is represented by any of the following formulas [VI-1] to [VI-21] 【Chemistry 24】 【Chemistry 25】 【Chemistry 26】 A pharmaceutical product containing, as an active ingredient, a compound according to any one of claims 4 to 7, a pharmaceutically acceptable salt thereof, or a hydrate thereof.

9. In the above formula [I], X is a carboxyl; W is a structure represented by the following formulas [III-4] to [III-11], [III-13] to [III-14], or [III-18] to [III-19]. 【Chemistry 27】 And; R ２ However, the base represented by the following formula [IV-1] or [IV-2] 【Chemistry 28】 And, Here, Ring B １ It is phenyl, R Ｂ１１ and R Ｂ１２ They are identically hydrogen atoms, L １ However, the structure is represented by the following formulas [V-3], [V-8], or [V-14]. 【Chemistry 29】 And, Here, n4 is 4, Also, Ring B ２ It is dihydroindenyl, R Ｂ２１ and R Ｂ２２ They are identically hydrogen atoms, L ２ The structure is represented by the following formula [V-20]. 【Transformation 30】 And, Here, n5 is 2; R ３ However, the stereochemical configuration is represented by the following equation [VII] 【Chemistry 31】 It is a methyl having; R ４ However, the base represented by the following formulas [VI-2], [VI-3], [VI-8], [VI-10] to [VI-12], [VI-16], [VI-19], or [VI-21] 【Chemistry 32】 【Transformation 33】 A pharmaceutical product containing, as an active ingredient, a compound according to any one of claims 4 to 7, a pharmaceutically acceptable salt thereof, or a hydrate thereof.

10. In the above formula [I], X is carboxyl or tetrazolyl; W is a structure represented by the following formulas [III-5], [III-8] to [III-11], or [III-13]. 【Transformation 34】 And; R ２ However, the base represented by the following formula [IV-1] or [IV-2] 【Chemistry 35】 And, Here, Ring B １ It is phenyl, R Ｂ１１ and R Ｂ１２ The same is true for hydrogen atoms And, L １ However, the structure is represented by the following formulas [V-3], [V-12], or [V-14]. 【Transformation 36】 And, Here, n4 is an integer of 4, Also, Ring B ２ It is dihydroindenyl, R Ｂ２１ and R Ｂ２２ They are identically hydrogen atoms, L ２ The structure is represented by the following formula [V-20]. 【Chemistry 37】 And, Here, n5 is 2; R ３ However, the stereochemical configuration is represented by the following equation [VII] 【Transformation 38】 It is a methyl having; R ４ However, the base represented by the following formulas [VI-2], [VI-7], [VI-8], [VI-10], [VI-11], or [VI-12] 【Chemistry 39】 A pharmaceutical product containing, as an active ingredient, a compound according to any one of claims 4 to 7, a pharmaceutically acceptable salt thereof, or a hydrate thereof.

11. A pharmaceutical product according to claim 1, containing any of the following compounds or pharmaceutically acceptable salts thereof, or hydrates thereof, as an active ingredient: 【Chemistry 40】 【Chemistry 41】 【Chemistry 42】 【Chemistry 43】 【Chemistry 44】

12. A pharmaceutical product according to claim 1, containing any of the following compounds or pharmaceutically acceptable salts thereof, or hydrates thereof, as an active ingredient: 【Chemistry 45】 【Chemistry 46】 【Chemistry 47】

13. The following formula [Ia] 【Chemistry 48】 {In the above formula [Ia], X is carboxy, C １－４ A structure selected from the following group of formulas [IIa]: alkoxycarbonyl, carbamoyl, tetrazolyl, or 【Chemistry 49】 Show; W is a linear C １－３ Alkanediyl, or a structure selected from the following group of formulas [IIIa] [Transformation 50] Show, Here, The linear C １－３ Alkandiyl is C １－６ Alkyl (the C １－６ The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and carboxyl groups. １－６ Alkyl, C ３－８ Cycloalkyl, phenyl C １－３ Alkyl and pyridyl C １－３ It may be substituted with one group selected from the group consisting of alkyl groups. And the linear C １－３ If the alkanediyl is substituted with one methyl group, it may be further substituted with one methyl group. Ring A １ , ring A ２ , and ring A ３ C ３－８ This refers to a cycloalkane, a partially saturated 9-10 membered fused hydrocarbon aromatic ring, a 4-8 membered saturated heterocycle containing an oxygen atom, a partially saturated 9-10 membered fused saturated heterocycle containing an oxygen atom, a 4-8 membered saturated heterocycle containing a sulfur atom, a partially saturated 9-10 membered fused saturated heterocycle containing a nitrogen atom, a 4-8 membered saturated heterocycle containing a nitrogen atom, or a partially saturated 9-10 membered fused saturated heterocycle containing a sulfur atom. Here, Each sulfur atom in the saturated heterocycle of a 4-8 member containing the sulfur atom and the saturated heterocycle of a 9-10 member fused ring containing a partially saturated sulfur atom may be substituted with 1-2 oxos. Also, Each nitrogen atom in the saturated heterocycle of a 4-8 member containing the nitrogen atom and the saturated heterocycle of a 9-10 member fused ring containing a partially saturated nitrogen atom is C １－４ Alkylcarbonyl and C １－４ It may be substituted with one group selected from the group consisting of alkoxycarbonyls. R Ａ１１ , R Ａ２１ , and R Ａ３１ These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C １－６ Alkyl, C １－６ Alkoxy, C １－６ Alkyl carbonyl, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C １－３ It may be substituted with alkyl. R Ａ１２ , R Ａ２２ , and R Ａ３２ These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ These may each combine to form an oxo, Furthermore, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ Each of these combines with a carbon atom in the adjacent ring A to form C ３－６ They may also form cycloalkanes; R １ This represents a hydrogen atom or a methyl atom; R ２ C １－１０ Alkyl, C ２－１０ Alkenil, C ２－１０ Alkynyl or the group represented by the following formula [IVa] 【Chemistry 51】 Show, Here, Ring B is C ３－８ The terms represent cycloalkyl, 4-8 member saturated heterocyclyl, phenyl, 9-10 member fused aryl, 5-6 member heteroaryl, or 9-10 member fused heteroaryl. R Ｂ１ and R Ｂ２ These are, independently, hydrogen atoms, halogen atoms, and C １－６ Alkyl, C １－６ It shows an alkoxy, L is C １－２ Alkanedil (the C １－２ The alkanediyl may be substituted with 1 to 4 fluorine atoms. ３－８ Alkanedil (the C ３－８ The alkanediyl may be substituted with 1 to 5 fluorine atoms. (Formula [V-6]: -CH ２ CH ２ CH = C(CH ３ A structure represented by ) or a structure represented by the following formula [V-1a] 【Chemistry 52】 Show, Here, n1 represents an integer between 0 and 3. n2 represents an integer between 0 and 5. n3 represents an integer between 0 and 3. Also, C ３－８ R is one of the carbon atoms in alkanediyl. ２ The atom that is two or more atoms away from the nitrogen atom to which it is bonded is of the formula -O-, formula -S-, or formula -N(R Ｌ１ ) - can be replaced with, moreover, C ３－８ R is one of the two consecutive carbon atoms in an alkanediyl. ２ The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined as -C(=O)N(R) Ｌ２ ) - can be replaced with, R Ｌ１ is a hydrogen atom or C １－３ It indicates alkyl, R Ｌ２ is a hydrogen atom or C １－３ It indicates alkyl; R ３ is a hydrogen atom or C １－３ Alkyl (the C １－３ The alkyl group may be substituted with one group selected from the group consisting of hydroxyl and methoxy. R ４ The base is represented by the following formula [VIa] 【Chemistry 53】 Show, Here, Ring C represents a phenyl group, a 9-10 member fused aryl group, a 5-6 member heteroaryl group, or a 9-10 member fused heteroaryl group. The phenyl is a hydroxy, carboxy, carbamoyl, cyano, halogen atom, C １－６ Alkyl (the C １－６ Alkyl is hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. ), Halo C １－６ Alkyl (the halo C １－６ Alkyl is hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. ２－６ Alkenil, C ２－６ Alkinyl, C ３－８ Cycloalkyl (the C ３－８ Cycloalkyls are hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. １－６ Alkoxy, Halo C １－６ Alkoxy (the C １－６ Alkoxy and Halo C １－６ Alkoxy is composed of hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. ３－８ Cycloalkoxy (the C ３－８ Cycloalkoxys are composed of hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. １－６ Alkyl sulfanyl, C １－６ Alkyl sulfinyl, C １－６ Alkyl sulfonyl (the C １－６ Alkyl sulfanyl, C １－６ Alkyl sulfinyl, and C １－６ Alkylsulfonyls are hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. ), monoC １－６ Alkylamino, diC １－６ Alkylamino (the mono C １－６ Alkylamino and diC １－６ Alkylaminos are hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys. １－６ Alkylcarbonyl, Halo C １－６ Alkylcarbonyl, C １－６ Alkoxycarbonyl, monoC １－６ Alkylaminocarbonyl and diC １－６ Alkylaminocarbonyl (the C １－６ Alkylcarbonyl, Halo C １－６ Alkylcarbonyl, C １－６ Alkoxycarbonyl, monoC １－６ Alkylaminocarbonyl and diC １－６ Alkylaminocarbonyl is a compound of hydroxy and C １－６ It may be substituted with one group selected from the group consisting of alkoxys.) It may also be substituted with one to four groups selected identically or differently from the group consisting of alkoxys. The aryl group of the 9-10 member fused ring is a halogen atom, C １－６ Alkyl and C １－６ They may be substituted with one to three groups selected identically or differently from the group consisting of alkoxys. The 5-6 member heteroaryl group consists of a halogen atom, cyano, and C. １－６ Alkyl, C １－６ They may be substituted with one to three groups selected identically or differently from the group consisting of alkoxys and oxos. The 9-10 member fused ring heteroaryl is C １－６ Alkyl, C １－６ They may be substituted with one to four groups selected identically or differently from the group consisting of alkoxys and oxos; Also, R ３ and R ４ These, together with the adjacent carbon atoms, A partially saturated 9-10 member fused hydrocarbon aromatic ring or a partially saturated 9-10 member fused heteroaromatic ring may be formed. Here, The partially saturated 9-10 membered fused hydrocarbon aromatic ring may be substituted with 1-2 halogen atoms. The partially saturated 9-10 member heteroaromatic ring may be substituted with 1-2 halogen atoms. An LPA1 receptor antagonist containing a compound represented by , a pharmaceutically acceptable salt thereof, or a hydrate thereof as an active ingredient.

14. In the group of equations relating W [IIIa], R Ａ１１ , R Ａ２１ , and R Ａ３１ These are, independently, a hydrogen atom, a hydroxyl atom, a carboxyl atom, a halogen atom, and C １－６ Alkyl, C １－６ Alkoxy, or a 4-6 member saturated heterocycline containing a nitrogen atom (the 4-6 member saturated heterocycline containing a nitrogen atom contains one C １－３ It may be substituted with alkyl. R Ａ１２ , R Ａ２２ , and R Ａ３２ These independently represent a hydrogen atom, a halogen atom, or a methyl atom. Also, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ These may each combine to form an oxo, moreover, R Ａ１１ and R Ａ１２ , R Ａ２１ and R Ａ２２ , and R Ａ３１ and R Ａ３２ Each of these combines with a carbon atom in the adjacent ring A to form C ３－６ They may form cycloalkanes, R ２ In equation [IVa] relating to, L is C １－２ Alkanedil (the C １－２ The alkanediyl may be substituted with 1 to 4 fluorine atoms. ３－８ Alkanedil (the C ３－８ The alkanediyl may be substituted with 1 to 5 fluorine atoms. ), or the structure represented by formula [V-1a], where, C ３－８ R is one of the carbon atoms in alkanediyl. ２ The atom that is two or more atoms away from the nitrogen atom to which it is bonded is of the formula -O-, formula -S-, or formula -N(R Ｌ１ ) - can be replaced with, moreover, C ３－８ R is one of the two consecutive carbon atoms in an alkanediyl. ２ The atom that is one or more atoms away from the nitrogen atom to which it is bonded is defined as -C(=O)N(R) Ｌ２ ) - can be replaced with, R Ｌ１ is a hydrogen atom or C １－３ It indicates alkyl, R Ｌ２ is a hydrogen atom or C １－３ An LPA1 receptor antagonist according to claim 13, wherein the alkyl group is represented.

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