3-phenylpropylamine derivatives

Abstract

To provide a novel compound having SF-1 antagonist activity, and a polyfunctional molecule comprising a moiety corresponding to this compound, particularly an SF-1 degrader.SOLUTION: The present invention provides a 3-phenylpropylamine derivative compound represented by formula (1), and a polyfunctional molecule comprising a moiety corresponding to the compound represented by formula (1). [In the formula, A is -O-, -S-, -NRa-, or -CRbRc-; the ring Q1 is a monocyclic or bicyclic aromatic hydrocarbon ring, a monocyclic or bicyclic aromatic heterocycle, a cycloalkane ring, a heterocycloalkane ring, a cycloalkene ring, or a heterocycloalkene ring; and the ring Q2 is a monocyclic or bicyclic aromatic hydrocarbon ring, a monocyclic or bicyclic aromatic heterocycle, a cycloalkane ring, a heterocycloalkane ring, a cycloalkene ring, a heterocycloalkene ring, a spirocycloalkane ring, or a spiroheterocycloalkane ring].SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to novel compounds having SF-1 antagonist activity, polyfunctional molecules containing a portion equivalent to said compound, particularly SF-1 degradation inducers, and pharmaceutical compositions containing these. [Background technology]

[0002] Steroidogenic factor 1 (also known as "SF1" or "SF-1") is a nuclear receptor expressed in the adrenal cortex, gonads, hypothalamus, and pituitary gland, and is an important molecule for the development of the adrenal glands and gonads (Non-Patent Literature 1). Adrenal tumors develop in mice that overexpress SF-1 (Non-Patent Literature 2), and there have been reports of SF-1 protein overexpression in adrenocortical cancer tissue (Non-Patent Literature 3), suggesting that SF-1 contributes to the development and progression of adrenal tumors. On the other hand, SF-1 has been shown to regulate the expression of steroid hormone synthases such as CYP11A1 and CYP17A1 in the adrenal cortex and testes, and to induce the production of steroid hormones such as androgens (Non-Patent Literature 4, 5). Androgens are important for the development and proliferation of prostate cancer, and although progression is suppressed by hormone therapy such as castration in the early stages of treatment, it progresses to castration-resistant prostate cancer that is resistant to hormone therapy. The proliferation of castration-resistant prostate cancer is known to be dependent on androgens derived from the adrenal glands (Non-Patent Literature 6).

[0003] On the other hand, in recent years, the usefulness of heterobifunctional molecules, in which a portion that binds to a target protein and a portion that recruits endogenous effector molecules are linked via a linker, has been reported. Heterobifunctional molecules exert the desired effect by causing changes in the target protein by physically bringing the target protein and endogenous effector molecules into close proximity (Non-Patent Literature 7).

[0004] One technique that utilizes such heterobifunctional molecules is Targeted Protein Degradation (TPD). TPD is a technique that induces the degradation of target proteins. It uses a heterobifunctional molecule in which a binder portion that binds to the target protein and a binder portion that binds to an E3 ligase are linked by a linker. This induces the formation of a complex between the target protein and the E3 ligase in cells, thereby inducing ubiquitination and degradation of the target protein and exhibiting potent physiological activity. More than 600 types of E3 ligases have been identified, but only a limited number are used in TPD, particularly cereblon (CRBN) and von Hippel-Lindau (VHL) (Non-Patent Literature 8). In particular, the binder portion that binds to CRBN (also called "CRBN ligand") is widely used in TPD, and its diverse structures and usefulness have been reported (Patent Literature 1-9, Non-Patent Literature 9). A variety of proteins have been reported as targets in TPD, but no target protein degradation inducers targeting SF-1 have been reported to date. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] International Publication No. 2017 / 197051 [Patent Document 2] International Publication No. 2018 / 237026 [Patent Document 3] International Publication No. 2019 / 060693 [Patent Document 4] International Publication No. 2019 / 060742 [Patent Document 5] International Publication No. 2019 / 099868 [Patent Document 6] International Publication No. 2019 / 199816 [Patent Document 7] International Publication No. 2020 / 210630 [Patent Document 8] International Publication No. 2022 / 081927

Patent Document 9

Non-licensed literature

[0006] [Non-licensed document 1] Parker KL, Schimmer BP, Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev., 1997; 18: 361-77. [Non-licensed document 2] Doghman M, Karpova T, Rodrigues GA, et al., Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endocrinol., 2007; 21: 2968-87. [Non-licensed document 3] Sbiera S, Schmull S, Assie G, et al., High Diagnostic and Prognostic Value of Steroidogenic Factor-1 Expression in Adrenal Tumors. J Clin Endocrinol Metab., 2010; 95: E161-71.

Non-licensed Document 4

Non-licensed Document 5

[0007] An object of the present invention is to provide a novel compound having SF-1 antagonist activity, a polyfunctional molecule containing a portion corresponding to the compound, and in particular an SF-1 degradation inducer (SF-1 Degrader). A further object of the present invention is to provide a composition for inhibiting SF-1, a composition for inducing the degradation of SF-1, or a pharmaceutical composition containing the compound or polyfunctional molecule. Another object of the present invention is to provide a method for treating a disease (in particular cancers such as castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism) comprising administering the compound or polyfunctional molecule. Yet another object of the present invention is to provide an intermediate that can be used in the production of the compound or polyfunctional molecule. [Means for solving the problem]

[0008] As a result of diligent research, the present inventors have found that a 3-phenylpropylamine derivative compound represented by formula (1) below has SF-1 antagonist activity, and that a polyfunctional molecule containing a portion corresponding to the compound represented by formula (1) can degrade SF-1 protein and inhibit the proliferation of tumor cells, thereby completing the present invention. In other words, the present invention relates to the following: [1] Formula (1):

[0009] [ka]

[0010] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -and, Here, R a is hydrogen or C 1-3 It is alkyl, R band R c is, independently of one another, hydrogen, halogen, or C 1-3 alkyl, and said alkyl is unsubstituted or substituted with 1 to 3 halogens, n R's 1 are, independently of one another, halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl)2, C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, where said alkyl and alkenyl are, independently of one another, unsubstituted or substituted with 1 to 3 halogens, said cycloalkyl and heterocycloalkyl are, independently of one another, unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3 are, independently of one another, hydrogen, halogen, C 1-6 alkyl, or C 2-6 alkenyl, where[[ID=[]]] said alkyl and alkenyl are, independently of one another, unsubstituted or substituted with 1 to 3 halogens, R 4 is C 1-6 alkyl, -C(=O)-R d (R d is C 1-6 alkyl, C 2-5 alkenyl, C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl), C 6-12 aryl, or 6- to 12-membered heteroaryl, Here, Said C 1-6 Alkyl is either unsubstituted or has 1 to 3 halogens, C 3-7 Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A cycloalkene ring, or a heterocycloalkene ring with 3 to 7 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L 1 These are single bonds, -O-, -S-, -NH-, and C 1-3 Alkilen, C 2-3 Alkenylenes are -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-. Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q 2 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C 5-12 The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 5 C 1-6 Alkyl, carboxy, hydroxy, or The following formula:

[0011] [ka]

[0012] It is a base represented by, Here, Said C 1-6 Alkyl is either unsubstituted or carboxy, hydroxy, and -OC. 1-6 It is substituted with one or two groups selected from the group consisting of alkyls, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof. [2] A is -O- or -CR b R c -The compound described in [1] or a pharmaceutically acceptable salt thereof. [3] n R 1 However, each is independent of halogen and -OC. 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A heterocycloalkyl compound described in [1] or [2] or a pharmaceutically acceptable salt thereof, wherein the heterocycloalkyl compound has 2, 3, or 7 members, wherein the heterocycloalkyl compound has 1 or 2 nitrogen atoms as ring member atoms. [4] R 2 and R 3 However, each independently, hydrogen or C 1-6 A compound described in any one of [1] to [3], or a pharmaceutically acceptable salt thereof, which is alkyl. [5] R 4 However, C 1-6 Alkyl, -C(=O)-R d , or a heteroaryl with 6 to 12 members, Here, The aforementioned R d C 1-6 It is alkyl, Said C 1-6 The alkyl group is either unsubstituted or contains 1 to 3 halogens or C atoms. 3-7 It is substituted with a cycloalkyl group, and The heteroaryl is a compound according to any one of [1] to [4] or a pharmaceutically acceptable salt thereof, having one or two nitrogen atoms as ring member atoms. [6] Ring Q 1 However, C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane ring, or C 3-7A compound according to any one of [1] to [5], or a pharmaceutically acceptable salt thereof, wherein the cycloalkene ring is the aromatic heterocycle having one or two nitrogen atoms as ring member atoms. [7] L 1 However, single bond, -O-, C 1-3 A compound described in any one of [1] to [6], or a pharmaceutically acceptable salt thereof, which is alkylene or -C(=O)-. [8] Ring Q 2 However, C 6-12 A monocyclic or bicyclic aromatic hydrocarbon ring, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A compound according to any one of [1] to [7] or a pharmaceutically acceptable salt thereof, comprising a cycloalkene ring or a 5- to 12-membered spiroheterocycloalkane ring, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring have one or two nitrogen atoms as ring member atoms. [9] The following equation (1'):

[0013] [ka]

[0014] [In the formula, A is -O- or -CF2-, R 1 may be substituted with halogens, or 1 to 3 halogens -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A 4- to 6-membered heterocycloalkyl group having 2 alkyl atoms or one nitrogen atom as a ring member atom. R 2 and R 3 These are, independently, hydrogen or C 1-6 It is alkyl, R 4 C may be substituted with 1 to 3 halogens. 1-6Alkyl, -C(=O)-C optionally substituted with 1 to 3 halogens 1-6 Alkyl, C optionally substituted with 1 trifluoromethyl 3-6 Cycloalkylmethyl, or 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring members (the heteroaryl may be optionally substituted with 1 halogen), Ring Q 1 is a benzene ring optionally having 1 or 2 groups selected from the group consisting of halogen and C 1-3 alkyl, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having 1 or 2 nitrogen atoms as ring members, C 4-7 cycloalkane ring, or C 4-7 cycloalkene ring, L 1 is a single bond, -O-, -CH2-, or -C(=O)-, Ring Q 2 is a benzene ring optionally substituted with 1 halogen, C 4-7 cycloalkane ring, C optionally substituted with 1 halogen 4-7 cycloalkene ring, piperidine ring, or 7-azaspiro[3.5]nonane ring, and R 5 is C optionally having 1 or 2 groups selected from the group consisting of carboxy, hydroxy and -O-C 1-6 alkyl, 1-6 alkyl, carboxy, hydroxy, or a group represented by the following formula:

[0015]

Chemical formula

[0016] a compound represented by ] or a pharmaceutically acceptable salt thereof.

[10] A is -O-, R 2 is methyl, R 3 is methyl, R 4However, C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 However, halogen and C 1-3 A benzene ring or pyridine ring which may have one group selected from the group consisting of alkyl groups, L 1 However, it is a single bond, -O-, or -C(=O)-, and Ring Q 2 However, the benzene ring, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring. The compounds described in [9] or their pharmaceutically acceptable salts.

[11] R 1 However, it is methoxy, and R 4 However, it is 3,3,3-trifluoro-2,2-dimethylpropyl. The compounds described in [9] or

[10] or their pharmaceutically acceptable salts.

[12] The following groups: trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid, 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid, {trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}pyridine-2-yl)oxy]cyclohexyl}acetic acid, [Trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexyl]acetic acid, (4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[biphenyl]-4-carboxylic acid, [(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methanol, and tert-butyl 4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-carboxylate Any one compound selected from or a pharmaceutically acceptable salt thereof.

[13] A polyfunctional molecule comprising a compound described in any one of [1] to

[12] or a portion equivalent to a pharmaceutically acceptable salt thereof.

[14] It further includes other functional components, the portion corresponding to the compound or a pharmaceutically acceptable salt thereof is R 5A polyfunctional molecule as described in

[13] , wherein at any point in the molecule, it is directly linked to other functional parts or linked via a linker.

[15] The polyfunctional molecule described in

[14] , wherein the other functional parts are an E3 ligase binding site, an autophagy-recruiting site, a lysosome-recruiting site, a kinase-recruiting site, a phosphatase-recruiting site, a glycosyltransferase-recruiting site, an acetyltransferase-recruiting site, or an ADC.

[16] The polyfunctional molecule described in

[14] , wherein the other functional part is the E3 ligase binding site.

[17] The polyfunctional molecule described in

[16] , wherein the E3 ligase binding site is a cereblon (CRBN) binding site.

[18] The following equation (2):

[0017] [ka]

[0018] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -and, Here, R a is hydrogen, or C 1-3 It is alkyl, R b and R c These are, independently, hydrogen, halogen, or C 1-3 It is alkyl, and The alkyl group is either unsubstituted or substituted with 1 to 3 halogens. n R 1 These are, independently, halogen, hydroxyl, -CN, and C. 1-6 Alkyl, C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(H)-C 1-3Alkyl, -N(C 1-3 Alkyl)2, C 3-7 Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 2 and R 3 These are, independently, hydrogen, halogen, and C. 1-6 Alkyl, or C 2-6 It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R 4 C 1-6 Alkyl, -C(=O)-R d (R d C 1-6 Alkyl, C 2-5 Alkenil, C 3-7 (representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C 6-12 It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C 1-6 Alkyl is either unsubstituted or has 1 to 3 halogens, C 3-7 Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A cycloalkene ring, or a heterocycloalkene ring with 3 to 7 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L 1 These are single bonds, -O-, -S-, -NH-, and C 1-3 Alkilen, C 2-3 Alkenylenes are -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-. Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q 2 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C 5-12The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aforementioned aromatic hydrocarbon rings, aromatic heterocycles, cycloalkane rings, heterocycloalkane rings, cycloalkene rings, heterocycloalkene rings, spirocycloalkane rings, and spiroheterocycloalkane rings are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. B is -L 2 -L 3 -L 4 -R 6 And, L 2 C is a single bond. 1-6 Alkylene, -C(=O)-, -C(=O)NH-, -(CH2) k -C(=O)NH- (where k is an integer from 1 to 3), or -NHC(=O)-, L 3 C is a single bond. 1-6 Alkilen, C 3-6 The cycloalkylene is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, L 4 These are single bonds, -NH-, -N(-R 7 )-(R 7 is C 1-6 It is alkyl, -CH2-, or -C(=O)-, and R 6 This is the E3 ligase binding site, autophagy-recruiting site, lysosome-recruiting site, kinase-recruiting site, phosphatase-recruiting site, glycosyltransferase-recruiting site, acetyltransferase-recruiting site, or ADC. A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof.

[19] A is -O- or -CR b R c -The compound described in

[18] or a pharmaceutically acceptable salt thereof.

[20] n R 1 However, each is independent of halogen and -OC. 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A heterocycloalkyl group comprising two, three, or seven members, wherein the heterocycloalkyl group has one or two nitrogen atoms as ring member atoms, as described in

[18] or

[19] , or a pharmaceutically acceptable salt thereof. [twenty one] R 2 and R 3 However, each independently, hydrogen or C 1-6 A compound described in any one of

[18] to

[20] , or a pharmaceutically acceptable salt thereof, which is alkyl. [twenty two] R 4 However, C 1-6 Alkyl, -C(=O)-R d , or a heteroaryl with 6 to 12 members, Here, The aforementioned R d C 1-6 It is alkyl, Said C 1-6 The alkyl group is either unsubstituted or contains 1 to 3 halogens or C atoms. 3-7 It is substituted with a cycloalkyl group, and The heteroaryl is a compound according to any one of

[18] to

[21] or a pharmaceutically acceptable salt thereof, having one or two nitrogen atoms as ring member atoms. [twenty three] Ring Q 1 However, C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane ring, or C3-7 A compound according to any one of

[18] to

[22] , or a pharmaceutically acceptable salt thereof, wherein the cycloalkene ring is the aromatic heterocycle having one or two nitrogen atoms as ring member atoms. [twenty four] L 1 However, single bond, -O-, C 1-3 A compound or pharmaceutically acceptable salt thereof described in any one of

[18] to

[23] , which is alkylene or -C(=O)-. [twenty five] Ring Q 2 However, C 6-12 A monocyclic or bicyclic aromatic hydrocarbon ring, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A compound according to any one of

[18] to

[24] or a pharmaceutically acceptable salt thereof, comprising a cycloalkene ring or a 5- to 12-membered spiroheterocycloalkane ring, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring have one or two nitrogen atoms as ring member atoms.

[26] The following equation (2'):

[0019] [ka]

[0020] [In the formula, A is -O- or -CF2-, R 1 may be substituted with halogens, or 1 to 3 halogens -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A 4- to 6-membered heterocycloalkyl group having 2 alkyl atoms or one nitrogen atom as a ring member atom. R 2 and R 3 These are, independently, hydrogen or C 1-6 It is alkyl, R 4 C may be substituted with 1 to 3 halogens. 1-6Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 A cycloalkylmethyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 is halogen and C 1-3 A benzene ring which may have one or two groups selected from the group consisting of alkyl groups, a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, L 1 These are single bonds, -O-, -CH2-, or -C(=O)-, Ring Q 2 This is a benzene ring which may be substituted with one halogen, C 4-7 A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. 4-7 A cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, B is -L 2 -L 3 -L 4 -R 6 And, L 2 C is a single bond. 1-6 Alkylene, -C(=O)-, -C(=O)NH-, -(CH2) k -C(=O)NH- (where k is an integer from 1 to 3), or -NHC(=O)-, L 3 C is a single bond. 1-6 Alkilen, C 3-6 The cycloalkylene is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, L 4 These are single bonds, -NH-, -N(-R 7 )-(R 7 is C1-6 It is alkyl, -CH2-, or -C(=O)-, and R 6 A compound represented by [where is an E3 ligase binding moiety, autophagy-recruiting moiety, lysosome-recruiting moiety, kinase-recruiting moiety, phosphatase-recruiting moiety, glycosyltransferase-recruiting moiety, acetyltransferase-recruiting moiety, or ADC] or a pharmaceutically acceptable salt thereof.

[27] R 6 However, the E3 ligase binding site is one of the compounds described in any one of

[18] to

[26] or a pharmaceutically acceptable salt thereof.

[28] The compound described in

[27] or a pharmaceutically acceptable salt thereof, wherein the E3 ligase binding site is a cereblon (CRBN) binding site.

[29] R 6 However, the following formula:

[0021] [ka]

[0022] [In the above formula, R 8 is hydrogen, or C 1-6 It is alkyl, W, X, Y, and Z are each independently a nitrogen atom, or a halogen, C 1-6 Alkyl and -OC 1-6 A carbon atom which may have one group selected from the group consisting of alkyl groups, l, m, and n each independently represent integers from 0 to 3, and The wavy line is L 4 A compound or a pharmaceutically acceptable salt thereof described in any one of

[18] to

[28] , which is one of the groups selected from [showing the bonding position with].

[30] R 6 However, the following formula:

[0023] [ka]

[0024] [In the formula, R 8 is hydrogen, or C 1-6 It is alkyl, V is a halogen, and The wavy line is L 4 The compound described in

[29] or a pharmaceutically acceptable salt thereof, which is one of the groups selected from [showing the bonding position with].

[31] R 1 However, it may be substituted with 1 to 3 halogens -OC 1-6 It is alkyl, R 4 However, C may be substituted with 1 to 3 halogens. 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 It is a cycloalkylmethyl, Ring Q 1 However, halogen and C 1-6 A benzene ring which may have one or two groups selected from the group consisting of alkyls, a 9- to 10-membered bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, and L 1 However, it is a single bond, or -O- The compounds described in any one of

[18] to

[30] or any pharmaceutically acceptable salt thereof.

[32] A is -O-, R 2 However, it is methyl, and R 3 However, it is methyl. A compound described in any one of

[18] to

[31] or a pharmaceutically acceptable salt thereof.

[33] R 1 However, it is methoxy, and R 4However, it is 3,3,3-trifluoro-2,2-dimethylpropyl. A compound or a pharmaceutically acceptable salt thereof as described in any one of

[18] to

[32] .

[34] Ring Q 1 However, it is a benzene ring which may have one halogen, L 1 However, it is a single bond, and Ring Q 2 However, it is a cyclohexene ring. A compound or a pharmaceutically acceptable salt thereof as described in any one of

[18] to

[33] .

[35] The following groups: 3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione, (3R)-3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione, (3S)-3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione, 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3R)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3S)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, 3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3R)-3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3S)-3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione, (3R)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione, and, (3S)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione Any one compound selected from or a pharmaceutically acceptable salt thereof. [35-2] The following groups: (3RS)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3R)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3S)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3S)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione 、 ( 3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, and, (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione Any one compound selected from or a pharmaceutically acceptable salt thereof.

[36] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione benzenesulfonate. [36-2] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione monobenzene sulfonate. [36-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione benzenesulfonate. [36-4] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione monobenzene sulfonate. [36-5] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione A benzenesulfonate crystal having peaks at diffraction angles (2θ) of 2.15±0.2, 8.30±0.2, 10.29±0.2, 14.75±0.2, 17.19±0.2, 20.00±0.2, 21.34±0.2, 22.68±0.2, 23.77±0.2, and 25.23±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [36-6] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione A benzenesulfonate crystal having peaks at diffraction angles (2θ) of 2.15±0.2, 8.30±0.2, 10.29±0.2, 14.75±0.2, 17.19±0.2, 20.00±0.2, 21.34±0.2, 22.68±0.2, 23.77±0.2, and 25.23±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[37] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione ethanesulfonate. [37-2] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione monoethanesulfonate. [37-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione ethanesulfonate. [37-4] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione monoethanesulfonate. [37-5] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione A crystal of ethanesulfonate, having peaks at diffraction angles (2θ) of 2.21±0.2, 12.04±0.2, 14.87±0.2, 17.69±0.2, 18.93±0.2, 20.41±0.2, 22.42±0.2, 23.19±0.2, 24.13±0.2, and 27.98±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [37-6] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione A crystal of ethanesulfonate, having peaks at diffraction angles (2θ) of 2.21±0.2, 12.04±0.2, 14.87±0.2, 17.69±0.2, 18.93±0.2, 20.41±0.2, 22.42±0.2, 23.19±0.2, 24.13±0.2, and 27.98±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[38] 3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione 10-camphor sulfonate. [38-2] 3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione-10-camphor sulfonate. [38-3] (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione 10-camphor sulfonate. [38-4] (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione - 10-camphor sulfonate. [38-5] 3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione Crystals of 10-camphor sulfonate, having peaks at diffraction angles (2θ) of 3.89±0.2, 6.81±0.2, 7.68±0.2, 8.20±0.2, 10.28±0.2, 13.15±0.2, 15.97±0.2, 16.81±0.2, 18.58±0.2, and 23.56±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [38-6] (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione Crystals of 10-camphor sulfonate, having peaks at diffraction angles (2θ) of 3.89±0.2, 6.81±0.2, 7.68±0.2, 8.20±0.2, 10.28±0.2, 13.15±0.2, 15.97±0.2, 16.81±0.2, 18.58±0.2, and 23.56±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[39] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione ethanesulfonate. [39-2] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione monoethanesulfonate. [39-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione ethanesulfonate. [39-4] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione monoethanesulfonate. [39-5] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A crystal of ethanesulfonate, having peaks at diffraction angles (2θ) of 2.27±0.2, 8.18±0.2, 9.88±0.2, 13.09±0.2, 14.57±0.2, 15.80±0.2, 16.91±0.2, 17.77±0.2, 18.87±0.2, and 20.14±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [39-6] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione ethanesulfonic acid salt A crystal having peaks at diffraction angles (2θ) of 2.27±0.2, 8.18±0.2, 9.88±0.2, 13.09±0.2, 14.57±0.2, 15.80±0.2, 16.91±0.2, 17.77±0.2, 18.87±0.2, and 20.14±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[40] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione salicylate. [40-2] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione monosalicylate. [40-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione salicylate. [40-4] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione monosalicylate. [40-5] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A salicylate crystal having peaks at diffraction angles (2θ) of 2.20±0.2, 4.34±0.2, 9.45±0.2, 10.97±0.2, 13.23±0.2, 16.98±0.2, 18.09±0.2, 20.20±0.2, 21.32±0.2, and 25.19±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [40-6] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione A salicylate crystal having peaks at diffraction angles (2θ) of 2.20±0.2, 4.34±0.2, 9.45±0.2, 10.97±0.2, 13.23±0.2, 16.98±0.2, 18.09±0.2, 20.20±0.2, 21.32±0.2, and 25.19±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[41] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione benzenesulfonate. [41-2] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione monobenzene sulfonate. [41-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione benzenesulfonate. [41-4] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione monobenzene sulfonate. [41-5] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A benzenesulfonate crystal having peaks at diffraction angles (2θ) of 2.19±0.2, 8.87±0.2, 10.86±0.2, 12.55±0.2, 13.05±0.2, 14.99±0.2, 17.84±0.2, 20.62±0.2, 21.43±0.2, and 25.27±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [41-6] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione A benzenesulfonate crystal having peaks at diffraction angles (2θ) of 2.19±0.2, 8.87±0.2, 10.86±0.2, 12.55±0.2, 13.05±0.2, 14.99±0.2, 17.84±0.2, 20.62±0.2, 21.43±0.2, and 25.27±0.2 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[42] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione 10-camphor sulfonate. [42-2] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione-10-camphor sulfonate. [42-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione 10-camphor sulfonate. [42-4] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione - 10-camphor sulfonate. [42-5] 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione Crystals of 10-camphor sulfonate, having peaks at diffraction angles (2θ) of 2.20±0.2, 7.82±0.2, 11.05±0.2, 12.42±0.2, 13.34±0.2, 15.23±0.2, 16.49±0.2, 17.86±0.2, 20.15±0.2, and 24.36±0.2 in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms). [42-6] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione Crystals of 10-camphor sulfonate, having peaks at diffraction angles (2θ) of 2.20±0.2, 7.82±0.2, 11.05±0.2, 12.42±0.2, 13.34±0.2, 15.23±0.2, 16.49±0.2, 17.86±0.2, 20.15±0.2, and 24.36±0.2 in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[43] A composition for inhibiting Steroidogenic Factor 1, comprising any one of the compounds described in [1] to

[12] or a pharmaceutically acceptable salt thereof, any one of the polyfunctional molecules described in any one of

[13] to

[17] , or any one of the compounds described in any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or crystals thereof.

[44] A composition for inducing the degradation of Steroidogenic Factor 1, comprising a polyfunctional molecule described in any one of

[13] to

[17] , or a compound described in any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or crystals thereof.

[45] A pharmaceutical composition containing a compound described in any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, a polyfunctional molecule described in any one of

[13] to

[17] , or a compound described in any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or crystals thereof.

[46] The pharmaceutical composition according to

[45] for the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism. [46-2] The pharmaceutical composition according to

[45] for the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, Cushing's syndrome, or primary aldosteronism.

[47] A method for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism, characterized by administering an effective amount of a compound described in any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, a polyfunctional molecule described in any one of

[13] to

[17] , or a compound described in any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or crystals thereof, to a subject requiring treatment for castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism. [47-2] A method for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, Cushing's syndrome, or primary aldosteronism, characterized by administering an effective amount of a compound described in any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, a polyfunctional molecule described in any one of

[13] to

[17] , or a compound described in any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or crystals thereof, to a patient requiring treatment for castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, Cushing's syndrome, or primary aldosteronism.

[48] Compounds described in any one of [1] to

[12] or pharmaceutically acceptable salts thereof, polyfunctional molecules described in any one of

[13] to

[17] , or compounds described in any one of

[18] to [42-6] or pharmaceutically acceptable salts thereof, or crystals thereof, for use in the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism. [48-2] Compounds described in any one of [1] to

[12] or pharmaceutically acceptable salts thereof, polyfunctional molecules described in any one of

[13] to

[17] , or compounds described in any one of

[18] to [42-6] or pharmaceutically acceptable salts thereof, or crystals thereof, for use in the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, Cushing's syndrome, or primary aldosteronism.

[49] Use of a compound or a pharmaceutically acceptable salt thereof described in any one of [1] to

[12] , a polyfunctional molecule described in any one of

[13] to

[17] , or a compound or a pharmaceutically acceptable salt thereof described in any one of

[18] to [42-6], or crystals thereof, in the manufacture of a pharmaceutical for the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism. [49-2] Use of a compound or a pharmaceutically acceptable salt thereof described in any one of [1] to

[12] , a polyfunctional molecule described in any one of

[13] to

[17] , or a compound or a pharmaceutically acceptable salt thereof described in any one of

[18] to [42-6], or crystals thereof, in the manufacture of a pharmaceutical for the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, Cushing's syndrome, or primary aldosteronism.

[50] Formula (10):

[0025] [ka]

[0026] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -and, Here, R a is hydrogen or C 1-3 It is alkyl, R b and R c These are, independently, hydrogen, halogen, or C 1-3 It is alkyl, and The alkyl group is either unsubstituted or substituted with 1 to 3 halogens. n R 1 These are, independently, halogen, hydroxyl, -CN, and C. 1-6 Alkyl, C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 Alkyl)2, C 3-7 Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 2 and R 3 These are, independently, hydrogen, halogen, and C. 1-6 Alkyl, or C 2-6 It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R 4 C 1-6 Alkyl, -C(=O)-R d (R d C 1-6 Alkyl, C 2-5 Alkenil, C 3-7 (representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C 6-12 It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C 1-6 Alkyl is either unsubstituted or has 1 to 3 halogens, C 3-7 Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A cycloalkene ring, or a heterocycloalkene ring with 3 to 7 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L 1 These are single bonds, -O-, -S-, -NH-, and C 1-3 Alkilen, C 2-3 Alkenylenes are -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-. Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q 2 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C 5-12 The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 10 C 1-6 It is alkyl, Here, Said C 1-6 The alkyl group is substituted with one or two 3- to 7-membered heterocycloalkyl groups. The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, and The heterocycloalkyl group is either unsubstituted or substituted with an amino group protecting group, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof. For example, if item numbers are indicated as a range, such as "

[18] to [42-6]" above, and there are items with sub-numbers like [36-3] or [42-4] within that range, then those items with sub-numbers are also included in that range. [Effects of the Invention]

[0027] The compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity and can therefore be used as an SF-1 antagonist or SF-1 inhibitor. Furthermore, since SF-1 is known to be involved in the development and progression of various diseases such as adrenocortical carcinoma and castration-resistant prostate cancer, the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof can be used in the treatment of such diseases. In addition, because the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity, it can be used as a substructure in a larger molecule (e.g., a polyfunctional molecule) by combining it with other functional moieties. Furthermore, the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof specifically binds to SF-1 and can therefore be used as an SF-1 binder. Additionally, by combining the portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof with other functional portions, it can be used as an SF-1 binding moiety in larger molecules (e.g., polyfunctional molecules). In particular, polyfunctional molecules containing the portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof and an E3 ligase binding portion, especially the compound represented by formula (2) or a pharmaceutically acceptable salt thereof, or their crystals, can degrade the SF-1 protein and inhibit the proliferation of tumor cells. Therefore, they can be used as SF-1 inhibitors and SF-1 degraders, and can also be used for the treatment of SF-1-related diseases such as adrenocortical carcinoma and castration-resistant prostate cancer. [Brief explanation of the drawing]

[0028] [Figure 1] Powder X-ray diffraction pattern of the crystal obtained in Example CI1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Figure 2] Powder X-ray diffraction pattern of the crystal obtained in Example CJ1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Figure 3] Powder X-ray diffraction pattern of the crystal obtained in Example CK1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Figure 4] Powder X-ray diffraction pattern of the crystal obtained in Example CL1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Figure 5] Powder X-ray diffraction pattern of the crystal obtained in Example CM1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Figure 6]Powder X-ray diffraction pattern of the crystal obtained in Example CN1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Figure 7] Powder X-ray diffraction pattern of the crystal obtained in Example CO1. The vertical axis of the figure shows the diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. [Modes for carrying out the invention]

[0029] <1.Definition> Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. In the event of any conflict between the meaning of a term as defined herein and the meaning commonly understood by those skilled in the art, the meaning defined herein shall prevail. Preferred methods and materials are described below, but similar or equivalent methods and materials may be used in carrying out or testing the present invention. All references (including patent and non-patent documents) cited herein are incorporated herein by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative and not intended to limit the scope of the invention.

[0030] In this specification, Steroidogenic factor 1 refers to the protein encoded by the NR5A1 gene and may be abbreviated or synonymous with SF-1, hSF-1, SF1, Ad4BP, AD4BP, ELP, FTZ1, TZF1, POF7, SPGF8, SRXX4, or SRXY3.

[0031] In this specification, "antagonist" means a substance that reduces, interferes with, or neutralizes the action, activity, or effect of another substance. Therefore, in this specification, "SF-1 antagonist" means a substance that reduces, interferes with, or neutralizes the action, activity, or effect of SF-1.

[0032] In this specification, "halogen" means fluorine (F), chlorine (Cl), bromine (Br), and iodine (I).

[0033] In this specification, "alkyl" means a linear or branched alkyl group. In this specification, "C 1-6 "Alkyl" refers to an alkyl group having 1 to 6 carbon atoms. 1-3 "Alkyl" refers to an alkyl group having one to three carbon atoms. Examples of alkyl groups include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, and n-hexyl.

[0034] In this specification, "alkylene" means a straight-chain or branched-chain alkylene. In this specification, "C 1-6 "Alkylene" refers to an alkylene having 1 to 6 carbon atoms, and is "C 1-3 "Alkylene" refers to an alkylene having one to three carbon atoms. Examples of "alkylenes" include, but are not limited to, methylene, ethylene, n-propylene, i-propylene, n-butylene, i-butylene, s-butylene, t-butylene, n-pentylene, and n-hexylene.

[0035] In this specification, “alkenyl” means a linear or branched alkenyl. In this specification, “C 2-6 "Alkenyl" refers to an alkenyl having 2 to 6 carbon atoms, and is "C 2-5 The term "alkenyl" refers to an alkenyl molecule having 2 to 5 carbon atoms. Examples of alkenyls include, but are not limited to, ethenyl (vinyl), 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, buta-2,3-dienyl, pentenyl, and hexenyl.

[0036] In this specification, "alkenylene" means a straight-chain or branched-chain alkenylene. In this specification, "C2-3 "Alkenylene" refers to an alkenylene having two to three carbon atoms. Examples of "alkenylenes" include, but are not limited to, etenylene (vinylene), 1-propenylene, 2-propenylene, 1-butenylene, 2-butenylene, 3-butenylene, buta-2,3-dienylene, pentenylene, and hexenylene.

[0037] In this specification, "haloalkyl" means an alkyl group substituted with one or more halogens. 1-3 "Haloalkyl" refers to a C atom substituted with one or more halogens. 1-3 Meaning alkyl ru. Examples of "haloalkyl" include trifluoromethyl, difluoromethyl, monofluoromethyl, pentafluoroethyl, tetrafluoroethyl, monofluoroethyl, trifluoroethyl, and trichloromethyl, but are not limited to these.

[0038] In this specification, “aromatic hydrocarbon ring” means a monocyclic or polycyclic hydrocarbon ring in which at least one of the rings is an aromatic ring. In this specification, “aryl” means a group derived from an aromatic hydrocarbon ring. 6-12 "Aryl" refers to an aryl group containing 6 to 12 carbon atoms as ring member atoms, and is called "C 6-12 The monocyclic or bicyclic aromatic hydrocarbon ring is 6 This refers to a monocyclic or bicyclic aromatic hydrocarbon ring containing 12 carbon atoms as ring member atoms. Examples of "aromatic hydrocarbon rings" include, but are not limited to, benzene, indene, naphthalene, and anthracene. Examples of "aryl" include, but are not limited to, phenyl, indenyl, naphthyl, and anthryl.

[0039] In this specification, “aromatic heterocycle” means a monocyclic or polycyclic ring in which at least one of the rings is an aromatic ring, and which includes one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur, as ring member atoms. In this specification, “heteroaryl” means a group derived from an aromatic heterocycle. “6- to 12-membered heteroaryl” means a heteroaryl consisting of 6 to 12 ring member atoms, and “6- to 12-membered monocyclic or bicyclic aromatic heterocycle” means a monocyclic or bicyclic aromatic heterocycle consisting of 6 to 12 ring member atoms. Examples of “aromatic heterocycles” include thiophene, pyrrole, pyrazole, triazole, and oxy sa Examples of heteroaryl compounds include, but are not limited to, zole, oxadiazole, thiazole, pyridine, pyrimidine, pyridazine, pyrazine, quinoline, quinoxaline, benzothiophene, benzimidazole, benzotriazole, and benzofuran. Examples of heteroaryl compounds include, but are not limited to, thienyl, pyrrolyl, pyrazolyl, triazolyl, oxazolyl, oxadiazolyl, thiazolyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, quinolyl, quinoxalyl, benzothiophenyl, benzimidazolyl, benzotriazolyl, and benzofuranil.

[0040] In this specification, "six-membered heteroaryl compounds having one or two nitrogen atoms as ring member atoms" can be defined as pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, and the like.

[0041] In this specification, "a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms" refers to, for example, pyridine, pyrazine, pyrimidine, Examples include, but are not limited to, six-membered rings such as pyridazine; seven-membered rings such as azepine, 1,2-diazepine, 1,3-diazepine, and 1,4-diazepine; eight-membered rings such as azosine; nine-membered rings such as azonine; six- and five-membered condensed rings such as indole, isoindole, indazole, benzimidazole, and imidazopyridine (including imidazo[1,2-a]pyridine); and six- and six-membered condensed rings such as quinoline, isoquinoline, quinazoline, quinoxaline, and sinnoline. In this specification, "9 to 10-membered bicyclic aromatic heterocycles having one or two nitrogen atoms as ring member atoms" include, but are not limited to, 6 / 5-membered fused rings such as indole, isoindole, indazole, benzimidazole, and imidazopyridine (including imidazo[1,2-a]pyridine); and 6 / 6-membered fused rings such as quinoline, isoquinoline, quinazoline, quinoxaline, and cinnoline.

[0042] In this specification, “cycloalkane ring” means a hydrocarbon ring that does not contain unsaturated bonds. In this specification, “cycloalkyl” means a monovalent group derived from a cycloalkane ring. A “cycloalkane ring” may be a monocyclic cycloalkane, a fused bicyclic cycloalkane, a spiro ring, or a bridged cycloalkane in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. In this specification, “C 3-7 "Cycloalkane ring" and "C 4-7 The term "cycloalkane ring" refers to a cycloalkane ring having 3 to 7 carbon atoms and 4 to 7 carbon atoms, respectively. 3-7 "Cycloalkyl" and "C 3-6 "Cycloalkyl" refers to a cycloalkyl group having 3 to 7 carbon atoms and 3 to 6 carbon atoms, respectively. 5-12 The term "spirocycloalkane ring" refers to a spirocycloalkane ring having 5 to 12 carbon atoms. Examples of "cycloalkane rings" include cyclobutane, cyclopentane, cyclohexane, and cycloheptane.

[0043] In this specification, "cycloalkylene" means a divalent group derived from a cycloalkane ring. In this specification, "C 3-6 "Cycloalkylene" refers to a cycloalkylene having 3 to 6 carbon atoms. Examples of "cycloalkylenes" include, but are not limited to, cyclobutylene, cyclopentylene, and cyclohexylene.

[0044] In this specification, “cycloalkene ring” means a hydrocarbon ring containing at least one carbon-carbon double bond. In this specification, “cycloalkene ring” may be a monocyclic cycloalkene, a fused bicyclic cycloalkene, or a bridged cycloalken in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. In this specification, “C 3-7 A "cycloalkene ring" refers to a cycloalkene ring having 3 to 7 carbon atoms, and is defined as "C 4-7 A "cycloalkene ring" refers to a cycloalkene ring having 4 to 7 carbon atoms. Examples of "cycloalkene rings" include, but are not limited to, cyclobutene, cyclobutadiene, cyclopentene, cyclopentadiene, cyclohexene, 1,3-cyclohexadiene, 1,4-cyclohexadiene, cycloheptene, 1,3-cycloheptadiene, 1,4-cycloheptadiene, and cycloheptatriene.

[0045] In this specification, “heterocycloalkane ring” means a saturated ring containing one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur, as ring member atoms. In this specification, “heterocycloalkyl” means a monovalent group derived from a heterocycloalkane ring. A “heterocycloalkane ring” may be a monocyclic heterocycloalkane, a fused bicyclic heterocycloalkane, a spiro ring, or a bridged heterocycloalkane in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. In this specification, "3- to 7-membered heterocycloalkane ring" means a heterocycloalkane ring having a total of 3 to 7 carbon atoms and heteroatoms as ring member atoms, "5- to 12-membered spiroheterocycloalkane ring" means a spiroheterocycloalkane ring having a total of 5 to 12 carbon atoms and heteroatoms as ring member atoms, and "3- to 7-membered heterocycloalkyl" means a heterocycloalkyl having a total of 3 to 7 carbon atoms and heteroatoms as ring member atoms.Examples of "heterocycloalkyl" compounds include oxyranil, thiaarnil, azilidinil, oxetanil, thiatanil, azetidinil, tetrahydrofuranil, tetrahydrothiophenyl, pyrrolidinil, tetrahydropyranil, pyranil, tetrahydrothiopyranil, thiopyranil, piperidinil, 1,4-dioxanil, 1,4-oxathianil, morpholinil, thiomorpholinil, and 1,4-dithia. Nyl, piperazinil, 1,4-azathanil, oxepanil, thiepanil, azepanil, 1,4-dioxepanil, 1,4-oxathiepanil, 1,4-oxazepanil, 1,4-dithiepanil, 1,4-thieazepanil, 1,4-azaphosfinanil, 1,4-diazepanil, 1,2-tetrahydrothiadin-2-yl, 1,3-tetrahydrothiadin-3-yl, tetrahydrothiadiazine, 1, 2-Tetrahydrodiazine-2-yl, 1,3-Tetrahydrodiazine-1-yl, Tetrahydroazepinyl, Chromanil, Clomenil, Isoxazolidinyl, 1,3-Oxazolidine-3-yl, Isothiazolidinyl, 1,3-Thiazolidine-3-yl, 1,2-Pyrazolidine-2-yl, 1,3-Pyrazolidine-1-yl, 7-Oxa-1-azaspiro[4,4]nonanyl, 3-Azabicyclo[3 Examples include hexanil, indolinil, dihydroindolinil, octahydro-1H-indolyl, octahydro-2H-pyrido[1,2-a]pyradinyl, 3-azabicyclo[4.1.0]heptanil, 3,4-dihydro-2H-pyranyl, 1,2,3,4-tetrahydropyridinyl, 1,2,5,6-tetrahydropyridinyl, tetrahydro-1H-benzo[d]azepinyl, etc.

[0046] In this specification, “heterocycloalkene ring” means a ring containing one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur, and containing at least one double bond. A “heterocycloalkene ring” may be a monocyclic heterocycloalkene, a fused bicyclic heterocycloalkene, a spiro ring, or a bridging heterocycloalkene in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. In this specification, “3-membered to 7-membered heterocycloalkene ring” means a heterocycloalkene ring having a total of 3 to 7 carbon atoms and heteroatoms as ring member atoms. Examples of “heterocycloalkene rings” include, but are not limited to, imidazoline, tetrahydropyridine, dihydropyridine, pyran, thiopyran, dihydropyran, dihydrofuran, dihydropyrazine, octahydroquinoline, octahydroisoquinoline, dihydrothiophene, dihydropyrroline, etc.

[0047] In this specification, unless otherwise specified, symbols will be used in a manner that will be obvious to those skilled in the art.

[0048] [ka]

[0049] This means that it is coupled on the other side of the page (α-configuration), and the symbol is:

[0050] [ka]

[0051] This means that the bonds are connected to the front side of the page (β-configuration). Also, three-dimensional symbols marked with an asterisk (for example, R * S * The symbols (etc.) indicate the relative spatial arrangement of the chiral center. The relative spatial arrangement is structurally represented by the symbol:

[0052] [ka]

[0053] It is written as follows.

[0054] In this specification, "pharmaceutically acceptable" means that it does not have significant toxicity and can be used as a pharmaceutical composition. Therefore, in this specification, "pharmaceutically acceptable salt" means a salt that does not have significant toxicity and can be used as a pharmaceutical composition.

[0055] In the present invention, "(3RS)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione" is "3 This refers to the same compound as "-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione".

[0056] In the present invention, "(3R)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione" is "(3R) This refers to the same compound as "-3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione".

[0057] In the present invention, "(3S)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione" is "(3S) This refers to the same compound as "-3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione".

[0058] In the present invention, "(3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione" is "3 This refers to the same compound as "-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione".

[0059] In the present invention, "(3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione" is "(3R) This refers to the same compound as "-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione".

[0060] In the present invention, "(3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione" is "(3S) This refers to the same compound as "-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione".

[0061] In the present invention, "(3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione" is "3 This refers to the same compound as "-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione".

[0062] In the present invention, "(3R)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione" is "(3R) This refers to the same compound as "-3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione".

[0063] In the present invention, "(3S)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione" is "(3S) This refers to the same compound as "-3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione".

[0064] In the present invention, "(3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione" is "3 This refers to the same compound as "-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione".

[0065] In the present invention, "(3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione" is "(3R) This refers to the same compound as "-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione".

[0066] In the present invention, "(3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione" is "(3S) This refers to the same compound as "-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione".

[0067] <2. SF-1 Antagonist> In one embodiment of the present invention, the following formula (1):

[0068] [ka]

[0069] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -and, Here, R a is hydrogen, or C 1-3 It is alkyl, R b and R c These are, independently, hydrogen, halogen, or C 1-3 It is alkyl, and The alkyl group is either unsubstituted or substituted with 1 to 3 halogens. n R 1 These are, independently, halogen, hydroxyl, -CN, and C. 1-6 Alkyl, C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 Alkyl)2, C 3-7 Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 2 and R 3 These are, independently, hydrogen, halogen, and C. 1-6 Alkyl, or C 2-6 It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R 4 C 1-6 Alkyl, -C(=O)-R d (R d C 1-6 Alkyl, C 2-5 Alkenil, C 3-7 (representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C 6-12 It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C 1-6 Alkyl is either unsubstituted or has 1 to 3 halogens, C 3-7 Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A cycloalkene ring, or a heterocycloalkene ring with 3 to 7 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L 1 These are single bonds, -O-, -S-, -NH-, and C 1-3 Alkilen, C 2-3 Alkenylenes are -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-. Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q 2 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C 5-12 The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 5 C 1-6 Alkyl, carboxy, hydroxy, or The following formula:

[0070] [ka]

[0071] It is a base represented by, Here, Said C 1-6 Alkyl is either unsubstituted or carboxy, hydroxy, and -OC. 1-6 It is substituted with one or two groups selected from the group consisting of alkyls, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof is provided.

[0072] In one embodiment of the present invention, A in formula (1) above is -O-, -S-, or -CR b R c - and preferably -O- or -CR b R c-, more preferably -O-, or -CF2-, and particularly preferably -O-.

[0073] In one embodiment of the present invention, R in formula (1) above a is hydrogen, or C 1-2 It is an alkyl group, preferably hydrogen, or methyl, more preferably hydrogen.

[0074] In one embodiment of the present invention, R in formula (1) above b and R c Each of these is independently hydrogen or a halogen, preferably a halogen, and more preferably F.

[0075] In one embodiment of the present invention, the n R in formula (1) above 1 These are, independently, halogen and -OC. 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 The R(alkyl) is a 2- or 3- to 7-membered heterocycloalkyl (where the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms), and in another embodiment of the present invention, the n R(alkyl) in formula (1) above 1 Each of these may be independently substituted with a halogen, or 1 to 3 halogens -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A 4- to 6-membered heterocycloalkyl group having one nitrogen atom as a ring member atom, preferably substituted with 1 to 3 halogens -OC 1-6 Alkyl, -N(C 1-3 Alkyl)2, or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member atom, more preferably substituted with 1 to 3 halogens -OC 1-6 It is alkyl, and more preferably -OC 1-3 It is alkyl, and most preferably methoxy.

[0076] In one embodiment of the present invention, R in formula (1) above 2 is hydrogen, or C 1-6 It is alkyl, preferably C 1-3 It is alkyl, more preferably methyl or ethyl, and even more preferably methyl.

[0077] In one embodiment of the present invention, R in formula (1) above 3 is hydrogen, or C 1-6 It is alkyl, preferably C 1-3 It is alkyl, more preferably methyl or ethyl, and even more preferably methyl.

[0078] In one embodiment of the present invention, R in formula (1) above 4 is either non-substitutive or C 3-7 Cycloalkyl-substituted C 1-6 Alkyl, -C(=O)-C 1-6 Alkyl, or a 6- to 12-membered heteroaryl (the heteroaryl having one or two nitrogen atoms as ring member atoms), and in another embodiment of the present invention, R in formula (1) above 4 C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 A cycloalkylmethyl or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), preferably a C which may be substituted with one to three halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), more preferably 3,3,3-trifluoro-2,2-dimethylpropyl, or -C(=O)-C which may be substituted with one to three halogens. 1-6It is alkyl, most preferably 3,3,3-trifluoro-2,2-dimethylpropyl.

[0079] In one embodiment of the present invention, the ring Q in formula (1) above 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles (the aromatic heterocycle having 1 or 2 nitrogen atoms as ring member atoms), C 3-7 Cycloalkane ring, or C 3-7 A cycloalkene ring, and in another embodiment of the present invention, ring Q in formula (1) above. 1 is halogen and C 1-3 A benzene ring which may have one or two groups selected from the group consisting of alkyl groups, a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 A cycloalkene ring, preferably a halogen and C 1-3 A benzene ring or pyridine ring which may have one substituent selected from the group consisting of alkyl groups, more preferably halogen and C 1-3 A benzene ring which may have one substituent selected from the group consisting of alkyl groups, and is particularly preferably a benzene ring.

[0080] In one embodiment of the present invention, L in formula (1) above 1 Preferably, a single bond, -O-, C 1-3 The bond is alkylene- or -C(=O)-, more preferably a single bond, -O-, -CH2-, or -C(=O)-, even more preferably a single bond, -O-, or -C(=O)-, and particularly preferably a single bond.

[0081] In one embodiment of the present invention, the ring Q in formula (1) above 2 C 6-12 A monocyclic or bicyclic aromatic hydrocarbon ring, C 3-7Cycloalkane ring, 3- to 7-membered heterocycloalkane ring (the heterocycloalkane ring has 1 or 2 nitrogen atoms as ring member atoms), C 3-7 A cycloalkene ring, or a 5- to 12-membered spiroheterocycloalkane ring (the spiroheterocycloalkane ring having one or two nitrogen atoms as ring member atoms), and in another embodiment of the present invention, ring Q in formula (1) above. 2 This is a benzene ring which may be substituted with one halogen, C 4-7 A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. 4-7 The ring is a cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, preferably a benzene ring, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, and more preferably C 4-7 It is a cycloalkene ring.

[0082] In one embodiment of the present invention, R in formula (1) above 5 Preferably, carboxy, or carboxy, hydroxy and -OC 1-6 C may be substituted with one or two groups selected from the group consisting of alkyl groups. 1-6 C may be substituted with an alkyl group, more preferably a carboxyl group, or one group selected from the group consisting of carboxyl and hydroxyl. 1-6 C may be substituted with an alkyl group, and more preferably with one group selected from the group consisting of carboxy and hydroxyl. 1-6 It is alkyl.

[0083] In one embodiment of the present invention, in formula (1) above, A is -O-, R 2 However, it is methyl, R 3 However, it is methyl, R 4 However, C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 However, halogen and C 1-3 A benzene ring or pyridine ring which may have one substituent selected from the group consisting of alkyl groups, L 1 However, it is a single bond, -O-, or -C(=O)-, and Ring Q 2 However, the benzene ring, C 4-7 Cycloalkane ring, or C 4-7 A compound or a pharmaceutically acceptable salt thereof, which is a cycloalkene ring, is provided.

[0084] In another embodiment of the present invention, in formula (1) above, R 1 However, it is methoxy, and R 4 However, a compound or a pharmaceutically acceptable salt thereof is provided, which is 3,3,3-trifluoro-2,2-dimethylpropyl.

[0085] In another embodiment of the present invention, the compound represented by formula (1) or a pharmaceutically acceptable salt thereof is the compound represented by the following formula (1') or a pharmaceutically acceptable salt thereof. Therefore, in one embodiment of the present invention, the following formula (1'):

[0086] [ka]

[0087] [In the formula, A is -O- or -CF2-, R 1 may be substituted with halogens, or 1 to 3 halogens -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A 4- to 6-membered heterocycloalkyl group having 2 alkyl atoms or one nitrogen atom as a ring member atom. R 2 and R 3 These are, independently, hydrogen or C 1-6 It is alkyl, R 4 C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 A cycloalkylmethyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 is halogen and C 1-3 A benzene ring which may have one or two groups selected from the group consisting of alkyl groups, a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, L 1 These are single bonds, -O-, -CH2-, or -C(=O)-, Ring Q 2 This is a benzene ring which may be substituted with one halogen, C 4-7 A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. 4-7 A cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, and R 5 These are carboxy, hydroxy, and -OC. 1-6 C may have one or two groups selected from the group consisting of alkyl groups. 1-6 Alkyl, carboxyl, hydroxyl, or the following formula:

[0088] [ka]

[0089] A compound represented by [a group represented by ] or a pharmaceutically acceptable salt thereof is provided.

[0090] Since formula (1') corresponds to a sub-concept of formula (1), the definitions, descriptions, preferred embodiments, etc., for each group in formula (1) above all apply to each group in formula (1') as well. Furthermore, in this specification, when "compound represented by formula (1)" is referred to without any particular reservation, this refers to a concept that also includes "compound represented by formula (1')", in other words, "compounds represented by formula (1) and formula (1')".

[0091] In another embodiment of the present invention, in formula (1') above, A is -O-, R 2 However, it is methyl, R 3 However, it is methyl, R 4 However, C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 However, halogen and C 1-3 A benzene ring or pyridine ring which may have one substituent selected from the group consisting of alkyl groups, L 1 However, it is a single bond, -O-, or -C(=O)-, and Ring Q 2 However, the benzene ring, C 4-7 Cycloalkane ring, or C 4-7 A compound or a pharmaceutically acceptable salt thereof, which is a cycloalkene ring, is provided.

[0092] In yet another embodiment of the present invention, in formula (1') above, R 1 However, it is methoxy, and R 4However, a compound or a pharmaceutically acceptable salt thereof is provided, which is 3,3,3-trifluoro-2,2-dimethylpropyl.

[0093] In yet another embodiment of the present invention, the following group: trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid, 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid, {trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}pyridine-2-yl)oxy]cyclohexyl}acetic acid, [Trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexyl]acetic acid, (4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[biphenyl]-4-carboxylic acid, [(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methanol, and tert-butyl 4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-carboxylate A compound selected from the above, or a pharmaceutically acceptable salt thereof, is provided. These compounds all correspond to the compounds represented by formulas (1) and (1') above, or pharmaceutically acceptable salts thereof.

[0094] <3. Multifunctional molecules> As described above, the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity and can therefore be used as a substructure in larger molecules (e.g., polyfunctional molecules) by combining it with other functional moieties. In particular, the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof binds specifically to SF-1 and can therefore be used as an SF-1 binding site in larger molecules (e.g., polyfunctional molecules) by combining it with other functional moieties.

[0095] Therefore, in one aspect of the present invention, a polyfunctional molecule is provided that includes a portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof.

[0096] The compound represented by formula (1) is structurally complete in itself; therefore, when linking it with other substructures, it is necessary to remove a specific atom or group of atoms from any point in the compound. For example, when linking a carboxyl group at the end of the compound represented by formula (1) with an amino group in another substructure by dehydration condensation, the "part corresponding to the compound represented by formula (1)" in the linked molecule is structurally different from the compound represented by formula (1) in that the "-OH" portion of the carboxyl group is removed. In this specification, the compound represented by formula (1) or its pharmaceutically acceptable salt, which has had a specific atom or group of atoms removed as a result of the linking reaction, is referred to as the "part corresponding to the compound represented by formula (1) or its pharmaceutically acceptable salt."

[0097] The linking point when linking the compound represented by formula (1) to other substructures (for example, the E3 ligase binding site or the linker site for linking to the E3 ligase binding site) is not particularly limited as long as it maintains the function of the compound represented by formula (1), especially the SF-1 inhibitory activity and SF-1 binding activity, but preferably R 5 Any part in can be cited. Therefore, in one embodiment of the present invention, the polyfunctional molecule of the present invention has a portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof, R 5 At any point in the R, it is either directly connected to other functional parts or connected via a linker. 5 Any location in is preferably R 5 Examples include the carboxyl portion or the amine portion in the above.

[0098] In the present invention, "polyfunctional molecule" means a molecule containing two or more parts having specific functions (functionality). As described above, the part corresponding to the compound represented by formula (1) of the present invention or its pharmaceutically acceptable salt has SF-1 antagonist activity and SF-1 binding activity, so the polyfunctional molecule of the present invention also contains at least one other functional part having a specific function. When there is one other functional part, the polyfunctional molecule of the present invention is a "bifunctional molecule," and when there are two, three, and four other functional parts, the polyfunctional molecule of the present invention is a "trifunctional molecule," a "tetrafunctional molecule," and a "pentafunctional molecule," respectively. In one embodiment of the present invention, the polyfunctional molecule of the present invention is a bifunctional molecule, a trifunctional molecule, a tetrafunctional molecule, or a pentafunctional molecule, preferably a bifunctional molecule, a trifunctional molecule, or a tetrafunctional molecule, more preferably a bifunctional molecule or a trifunctional molecule, and particularly preferably a bifunctional molecule. Furthermore, the other functional portions may be portions having the same function as the portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof, or they may be portions having different functions. Accordingly, in one embodiment of the present invention, the polyfunctional molecule is a homopolyfunctional molecule, and in another embodiment, the polyfunctional molecule is a heteropolyfunctional molecule. In one embodiment of the present invention, the polyfunctional molecule of the present invention is preferably a heterobifunctional molecule or a heterotrifunctional molecule, and more preferably a heterobifunctional molecule.

[0099] Other functional moieties included in the polyfunctional molecule of the present invention are not particularly limited, but are preferably those that can reasonably be expected to enhance or complement the activity of the moiety having SF-1 inhibitory / binding activity when linked together. Examples of such other functional moieties include, but are not limited to, E3 ligase binding moieties (or E3 ligase-recruiting moieties), autophagy-recruiting moieties, lysosome-recruiting moieties, kinase-recruiting moieties, phosphatase-recruiting moieties, glycosyltransferase-recruiting moieties, or acetyltransferase-recruiting moieties, ADCs, etc. Furthermore, such other functional moieties may include, for example, substances that are useful exclusively for research purposes, such as specific molecular markers or radiolabels, or functional substituents for making the compound of formula (1) a prodrug.

[0100] In the present invention, the "binding portion" (e.g., "E3 ligase binding portion") means the portion that binds to the target substance (e.g., "E3 ligase"), and the "mobilization portion" (e.g., "E3 ligase-mobilization portion") means the portion that enables the mobilization of the target substance (e.g., "E3 ligase"). Since the portion that binds to the target substance can be used to mobilize the target substance, in one embodiment of the present invention, the "binding portion" and the "mobilization portion" are used interchangeably.

[0101] <4. E3 ligase binding portion> In the present invention, "E3 ligase" (or "E3 ubiquitin ligase") means a protein that recruits an E2 ubiquitin-conjugating enzyme carrying ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 protein to the substrate. A polyfunctional molecule in which a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof is linked to an E3 ligase binding portion can induce the degradation of SF-1. Therefore, in one embodiment of the present invention, a polyfunctional molecule comprising a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof, and other functional portions, wherein the portion corresponding to the compound or a pharmaceutically acceptable salt thereof is R 5 A polyfunctional molecule is provided, in which, at any point in the formula, it is directly linked to another functional part or linked via a linker, and the other functional part is an E3 ligase binding site. Although not intended to be theoretical, it is thought that when a polyfunctional molecule having a part corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof linked to an E3 ligase binding site is administered into a living organism, the polyfunctional molecule is thought to recruit both SF-1 and E3 ligase to form a ternary complex composed of SF-1, E3 ligase, and the polyfunctional molecule, thereby ubiquitinating SF-1 by placing SF-1 and E3 ligase in close proximity. Since ubiquitinated SF-1 is degraded by the endogenous proteasome system, it is thought that the polyfunctional molecule of the present invention, including an E3 ligase binding site, can induce the specific degradation of SF-1.

[0102] The technique of inducing the degradation of a target protein using a heterobifunctional molecule in which a binder portion that binds to a target protein (also called "Protein of Interest: POI") and a binder portion that binds to an E3 ligase are linked via an appropriate linker is collectively called Targeted Protein Degradation (TPD). Numerous studies have been reported on the types of E3 ligases to be targeted in this technique, various E3 ligase-binding sites suitable for recruiting the E3 ligase, linker structures suitable for linking the POI and the E3 ligase-binding site, and technical theories for designing such linker structures (for example, Patent Documents 1-9, Non-Patent Documents 7-9). The present invention is the first to report that SF-1 can be targeted and actually degraded using such a TPD platform, and in particular, presents a novel POI-binding site for such a TPD platform.

[0103] In the TPD platform, the POI binding portion and the E3 ligase binding portion each play almost independent and distinct roles. Therefore, when each block (part) that has been demonstrated to function is combined, there is a high probability that the desired effect will be obtained. Accordingly, as the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) in the polyfunctional molecule of the present invention, any E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) of any target protein degradation inducer that has been confirmed to be useful to date, for example, the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) disclosed in Patent Documents 1-9 and Non-Patent Documents 7-9 can be applied. Furthermore, the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) of heterobifunctional molecules such as ARV-471, ARV-110, CFT8634, CFT7455, CFT1946, ARV-766, AR-LDD, GT20029, NX-2127, HSK29116, BGB-16673, DT-2216, FHD-609, LNK01002, KT-474, KT-413, NX-5948, KT-333, CG001419, and CFT8919, which have been reported to have been subjected to clinical or preclinical trials, can also be applied.In other words, the portion corresponding to the compound of formula (1) of the present invention or a pharmaceutically acceptable salt thereof can be the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) of any target protein degradation inducer that has been proven useful to date, for example, the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) disclosed in Patent Documents 1-8, Non-Patent Documents 7-9, etc., or ARV-471, ARV-110, CFT8634, CFT7455, CFT1946, ARV-766, AR- When linked to the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) of heterobifunctional molecules such as LDD, GT20029, NX-2127, HSK29116, BGB-16673, DT-2216, FHD-609, LNK01002, KT-474, KT-413, NX-5948, KT-333, CG001419, and CFT8919, it can be reasonably expected that polyfunctional molecules (especially heterobifunctional molecules) with the desired SF-1 degradation activity can be obtained, although the degree of activity may differ.

[0104] More than 600 types of E3 ligases have been identified to date, but only a limited number are used in the TPD platform. While there are no particular limitations on the E3 ligase targeted by the polyfunctional molecule of the present invention, in one embodiment of the present invention, the E3 ligase targeted by the polyfunctional molecule of the present invention may be cereblon (CRBN), Von Hippel-Lindau (VHL), cellular inhibitor of apoptosis protein (cIAP), DDB1 and CUL4 associated factor 11 (DCAF11), DDB1 and CUL4 associated factor 15 (DCAF15), DDB1 and CUL4 associated factor 16 (DCAF16), Mouse double minute 2 homolog (MDM2), Kelch-like ECH-associated protein 1 (KEAP1), RING finger protein 4 (RNF4), RING finger protein 114 (RNF114), Aryl hydrocarbon receptor (AhR), or Fem-1 homolog B (FEM1B) can be mentioned, preferably CRBN, VHL, or cIAP, more preferably CRBN or VHL, and even more preferably CRBN. Thus, in one embodiment of the present invention, the E3 ligase binding portion is a CRBN binding portion, a VHL binding portion, a cIAP binding portion, a DCAF11 binding portion, a DCAF15 binding portion, a DCAF16 binding portion, an MDM2 binding portion, a KEAP1 binding portion, a RNF4 binding portion, a RNF114 binding portion, an AhR binding portion, or a FEM1B binding portion, preferably a CRBN binding portion, a VHL binding portion, or a cIAP binding portion, more preferably a CRBN binding portion or a VHL binding portion, and even more preferably a CRBN binding portion.

[0105] In the present invention, the "CRBN binding portion" can be any compound portion having any structure, as long as it exhibits the desired binding affinity to CRBN. For example, the CRBN binding portions disclosed in Patent Documents 1-9 and Non-Patent Documents 7-9 can be cited. For example, thalidomide, and its derivatives lenalidomide and pomalidomide, are known to exhibit binding affinity to CRBN. Therefore, in one embodiment of the present invention, the CRBN binding portion is selected from thalidomide, lenalidomide, pomalidomide, thalidomide derivatives, lenalidomide derivatives, and pomalidomide derivatives. In the present invention, "derivative" in the context of the E3 ligand binding portion means a derivative that has structural differences compared to the parent E3 ligand binding molecule, but maintains the desired binding activity to the target E3 ligase, or has higher binding activity to the target E3 ligase. Furthermore, compounds referred to as ARV-471, ARV-110, CFT8634, CFT7455, CFT1946, AR-LDD, NX-2127, KT-413, NX-5948, CG001419, and CFT8919 have been subjected to clinical or preclinical trials as target protein degraders or proteolysis targeting chimeras (PROTACs) containing a CRBN binding moiety. Therefore, in one embodiment of the present invention, the CRBN binding moiety may be the CRBN binding moiety in these compounds.

[0106] In one embodiment of the present invention, the E3 ligase binding portion (CRBN binding portion) in the present invention may be the one referred to in Non-Patent Document 9.

[0107] In one aspect of the present invention, examples of VHL binding moieties include VH032 (JD Sander and JK Joung, Nat. Biotechnol., 2014, 32, 347-355), VH101 (M. Toure and CM Crews, Angew. Chem., Int. Ed., 2016, 55, 1966-1973), VH298 (SL Schreiber, Cell, 2021, 184, 3-9), or derivatives thereof.

[0108] In one embodiment of the present invention, examples of cIAP binding moieties include MeBS (JA Doudna and E. Charpentier, Science, 2014, 346, 1258096), MV1 (Y. Fedorov, et al., RNA, 2006, 12, 1188-1196), LCL161 (AL Jackson, et al., J. Burchard, M. Mao, B. Li, G. Cavet and PS Linsley, Nat. Biotechnol., 2003, 21, 635-637), or derivatives thereof.

[0109] In one embodiment of the present invention, the DCAF11 binding moiety can be a ligand or derivative thereof disclosed in S. Khan, X. et al., Nat. Med., 2019, 25, 1938-1947.

[0110] In one embodiment of the present invention, the DCAF15 binding moiety may be E7820 (L. Snyder, American Association for Cancer Research Annual Meeting, April 2021) or a derivative thereof.

[0111] In one embodiment of the present invention, the DCAF16 binding moiety may be KB02 (G. Weng, et al., Nucleic Acids Res., 2021, 49, D1381-D1387) or a derivative thereof.

[0112] In one embodiment of the present invention, examples of MDM2 binding moieties include Nutlin-3a (JS Lazo and ER Sharlow, Annu. Rev. Pharmacol. Toxicol., 2016, 56, 23-40), Idasanutlin (L. Jin, W. Wang and G. Fang, Annu. Rev. Pharmacol. Toxicol., 2014, 54, 435-456), or derivatives thereof.

[0113] In one embodiment of the present invention, the KEAP1 binding moiety may include CDDO (RG Guenette, et al., Chem. Soc. Rev., 2022, 51, 5740-5756), ligands disclosed in L. Snyder, American Association for Cancer Research Annual Meeting, April 2021, or derivatives thereof.

[0114] In one embodiment of the present invention, the RNF4 binding moiety may be CCW-16 (I. Sosic, et al., Chem. Soc. Rev., 2022, 51, 3487-3534) or a derivative thereof.

[0115] In one embodiment of the present invention, the RNF114 binding moiety can be Nimbolide (M. Bekes, et al., Nat. Rev. Drug Discovery, 2022, 21, 181-200), EN219 (M. He, et al., Signal Transduction Targeted Ther., 2022, 7, 181), or derivatives thereof.

[0116] In one embodiment of the present invention, the AhR binding moiety may be beta-NF (K. Li and CM Crews, Chem. Soc. Rev., 2022, 51, 5214-5236) or a derivative thereof.

[0117] In one embodiment of the present invention, the FEM1B binding moiety may be EN106 (M. He, et al., Front. Cell Dev. Biol., 2021, 9, 685106) or a derivative thereof.

[0118] Furthermore, the E3 ligase binding portion in the present invention is represented by the formula (2) described later, where "R 6 It is also possible to adopt any of the structures defined as follows:

[0119] <5. Linker> In the polyfunctional molecule of the present invention, the portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof may be directly linked to other functional portions, as long as it performs the desired function (e.g., SF-1 inhibitory activity or SF-1 degradation activity), but it is preferable that it is linked via a linker. Accordingly, in one embodiment of the present invention, a polyfunctional molecule is provided in which the portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof and other functional portions (e.g., an E3 ligase binding portion) are directly linked or linked via a linker, preferably linked via a linker. The linker used in the polyfunctional molecule of the present invention is not particularly limited as long as it does not impair the desired function (e.g., SF-1 inhibitory activity or SF-1 degradation activity), and therefore, any linker structure that is reasonably expected not to impair the desired function (e.g., SF-1 inhibitory activity or SF-1 degradation activity) can be used.

[0120] As described above, in TPD platforms, the composition and length of the linker are known to affect the formation of a ternary complex of POI / heterobifunctional molecule / E3 ligase, the POI degradation induction activity, and target selectivity. Numerous linker structures used in target protein degradation inducers and technical theories for designing and optimizing them have been reported (e.g., Patent Documents 1-8, Non-Patent Documents 7-9). As described above, the present invention presents a novel POI binding site that can be used in such TPD platforms, and therefore, if a linker whose effectiveness has already been demonstrated is adopted, there is a high probability that the desired effect will be obtained. Therefore, in one embodiment of the present invention, the linker portion in the polyfunctional molecule of the present invention can be any linker portion of a target protein degradation inducer that has been confirmed to be useful to date, for example, the linker portions disclosed in Patent Documents 1-8 and Non-Patent Documents 7-9, or the linker portions of ARV-471, ARV-110, CFT8634, ARV-766, AR-LDD, GT20029, NX-2127, HSK29116, BGB-16673, DT-2216, FHD-609, LNK01002, KT-474, KT-413, NX-5948, KT-333, CG001419, CFT7455, CFT1946, or CFT8919 that have been reported to have been subjected to clinical or preclinical trials. For example, in one embodiment of the present invention, the linker is the linker structure shown in Table 2 of Non-Patent Document 8, specifically, the following formula:

[0121] [ka]

[0122] The structural motif may be selected from any of the following: (wherein n and m each independently represent an integer from 1 to 10). Generally, it is known that using a linker that is too short tends to reduce the efficiency of ternary complex formation (POI / heterobifunctional molecule / E3 ligase) and instead increase the tendency to form binary complex (POI / heterobifunctional molecule, or heterobifunctional molecule / E3 ligase). On the other hand, it is known that using a linker that is too long increases the spatial degree of freedom, reduces the efficiency of ternary complex formation, and also tends to decrease the overall stability of the molecule. Therefore, it is preferable to use a linker of an appropriate length in the present invention. From the above viewpoint, in one embodiment of the present invention, n and m in the above formula are each independently integers from 1 to 5; in another embodiment of the present invention, n and m in the above formula are each independently integers from 1 to 4; in yet another embodiment of the present invention, n and m in the above formula are each independently integers from 1 to 3; and in yet another embodiment of the present invention, n and m in the above formula are each independently integers from 1 or 2.

[0123] In the TPD platform, the binding sites of the linker to POI or the linker to E3-ligase are also known to affect the formation of the ternary complex of POI / heterobifunctional molecule / E3-ligase, the POI degradation-inducing activity, and the target selectivity. Generally, it is considered crucial to avoid linking the linker to the main active sites of the POI-binding or E3-ligase-binding sites, and to link the linker to solvent-exposed sites of the POI-binding or E3-ligase-binding sites. From this perspective, in the polyfunctional molecule of the present invention, the portion corresponding to the compound represented by formula (1) or its pharmaceutically acceptable salt is R 5 It is preferable that the linker is connected at any point in the R, and in particular, 5 It is preferable that the linker is connected to the carboxyl or amine portion. Furthermore, it is preferable to appropriately select the connection site between the linker and the E3 ligase binding portion from the above viewpoint, based on known reports.

[0124] In one embodiment of the present invention, the linker of the present invention is defined in formula (2) described later as "-L 2 -L 3 -L 4 -」 is also acceptable.

[0125] <6. SF-1 Degrader> In one embodiment of the present invention, the following formula (2):

[0126] [ka]

[0127] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -and, Here, R a is hydrogen or C 1-3 It is alkyl, R b and R c These are, independently, hydrogen, halogen, or C 1-3 It is alkyl, and The alkyl group is either unsubstituted or substituted with one to three halogens. n R 1 These are, independently, halogen, hydroxyl, -CN, and C. 1-6 Alkyl, C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 Alkyl)2, C 3-7 Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl groups are each independently either unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C.1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 2 and R 3 These are, independently, hydrogen, halogen, and C. 1-6 Alkyl, or C 2-6 It is alkenyl, Here, The alkyl and alkenyl groups are each independently either unsubstituted or substituted with one to three halogens. R 4 C 1-6 Alkyl, -C(=O)-R d (R d C 1-6 Alkyl, C 2-5 Alkenil, C 3-7 (representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C 6-12 It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C 1-6 Alkyl is either unsubstituted or has 1 to 3 halogens, C 3-7 Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A cycloalkene ring, or a heterocycloalkene ring with 3 to 7 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L 1 These are single bonds, -O-, -S-, -NH-, and C 1-3 Alkilen, C 2-3 Alkenylenes are -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-. Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q 2 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C 5-12 The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. B is -L 2 -L 3 -L 4 -R 6 And, L 2 C is a single bond. 1-6 Alkylene, -C(=O)-, -C(=O)NH-, -(CH2) k -C(=O)NH- (where k is an integer from 1 to 3), or -NHC(=O)-, L 3 C is a single bond. 1-6 Alkilen, C 3-6 The cycloalkylene is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, L 4 These are single bonds, -NH-, -N(-R 7 )-(R 7 is C 1-6 It is alkyl, -CH2-, or -C(=O)-, and R 6 This is the E3 ligase binding site, autophagy-recruiting site, lysosome-recruiting site, kinase-recruiting site, phosphatase-recruiting site, glycosyltransferase-recruiting site, acetyltransferase-recruiting site, or ADC. A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof is provided.

[0128] In one embodiment of the present invention, A in formula (2) above is -O-, -S-, or -CR b R c - and preferably -O- or -CR b R c-, more preferably -O- or -CF2-, and particularly preferably -O-.

[0129] In one embodiment of the present invention, R in formula (2) above a is hydrogen or C 1-2 It is an alkyl group, preferably hydrogen or methyl, and more preferably hydrogen.

[0130] In one embodiment of the present invention, R in formula (2) above b and R c Each of these is independently hydrogen or a halogen, preferably a halogen, and more preferably F.

[0131] In one embodiment of the present invention, the n R in formula (2) above 1 These are, independently, halogen and -OC. 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 The R(alkyl) is a 2- or 3- to 7-membered heterocycloalkyl (where the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms), and in another embodiment of the present invention, the n R(alkyl) in formula (1) above 1 Each of these may be independently substituted with a halogen, or 1 to 3 halogens -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A 4- to 6-membered heterocycloalkyl group having one nitrogen atom as a ring member atom, preferably substituted with 1 to 3 halogens -OC 1-6 Alkyl, -N(C 1-3 Alkyl)2, or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member atom, more preferably substituted with 1 to 3 halogens -OC 1-6 It is alkyl, and more preferably -OC 1-3 It is alkyl, and most preferably methoxy.

[0132] In one embodiment of the present invention, R in formula (2) above 2 is hydrogen or C 1-6 It is alkyl, preferably C 1-3 It is alkyl, more preferably methyl or ethyl, and even more preferably methyl.

[0133] In one embodiment of the present invention, R in formula (2) above 3 is hydrogen or C 1-6 It is alkyl, preferably C 1-3 It is alkyl, more preferably methyl or ethyl, and even more preferably methyl.

[0134] In one embodiment of the present invention, R in formula (2) above 4 These are either non-substitutive or C 3-7 C is substituted with a cycloalkyl group. 1-6 Alkyl, -C(=O)-C 1-6 Alkyl, or a 6- to 12-membered heteroaryl (the heteroaryl having one or two nitrogen atoms as ring member atoms), and in another embodiment of the present invention, R in formula (2) above 4 C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 A cycloalkylmethyl or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), preferably a C which may be substituted with one to three halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), more preferably 3,3,3-trifluoro-2,2-dimethylpropyl, or -C(=O)-C which may be substituted with one to three halogens. 1-6It is alkyl, most preferably 3,3,3-trifluoro-2,2-dimethylpropyl.

[0135] In one embodiment of the present invention, the ring Q in formula (2) above 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles (the aromatic heterocycle having 1 or 2 nitrogen atoms as ring member atoms), C 3-7 Cycloalkane ring, or C 3-7 A cycloalkene ring, and in another embodiment of the present invention, ring Q in formula (1) above. 1 is halogen and C 1-3 A benzene ring which may have one or two groups selected from the group consisting of alkyl groups, a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 A cycloalkene ring, preferably a halogen and C 1-3 A benzene ring or pyridine ring which may have one substituent selected from the group consisting of alkyl groups, more preferably halogen and C 1-3 A benzene ring which may have one substituent selected from the group consisting of alkyl groups, and is particularly preferably a benzene ring.

[0136] In one embodiment of the present invention, L in formula (2) above 1 Preferably, a single bond, -O-, C 1-3 The molecule is alkylene or -C(=O)-, more preferably a single bond, -O-, -CH2-, or -C(=O)-, even more preferably a single bond, -O-, or -C(=O)-, and particularly preferably a single bond.

[0137] In one embodiment of the present invention, the ring Q in formula (2) above 2 C 6-12 A monocyclic or bicyclic aromatic hydrocarbon ring, C 3-7Cycloalkane ring, 3- to 7-membered heterocycloalkane ring (the heterocycloalkane ring has 1 or 2 nitrogen atoms as ring member atoms), C 3-7 A cycloalkene ring, or a 5- to 12-membered spiroheterocycloalkane ring (the spiroheterocycloalkane ring having one or two nitrogen atoms as ring member atoms), and in another embodiment of the present invention, ring Q in formula (1) above. 2 This is a benzene ring which may be substituted with one halogen, C 4-7 A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. 4-7 The ring is a cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, preferably a benzene ring, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, and more preferably C 4-7 It is a cycloalkene ring.

[0138] In one embodiment of the present invention, L in formula (2) above 2 Preferably, C 1-6 Alkylene, -C(=O)-, or -C(=O)NH-, more preferably C 1-6 Alkylene, or -C(=O)-, and more preferably C 1-6 It is alkylene.

[0139] In one embodiment of the present invention, L in formula (2) above 3 The most preferred is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, more preferably piperazinediyl, piperazine-2-ondiyl, piperidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, even more preferably piperazinediyl or piperidinediyl, and particularly preferably piperazinediyl.

[0140] In one embodiment of the present invention, L in formula (2) above 4Preferably, is -NH-, -CH2-, or -C(=O)-, more preferably -NH- or -C(=O)-, and even more preferably -C(=O)-.

[0141] In one embodiment of the present invention, the above formula (2) contains "-L 2 -L 3 -L 4 -」 is expressed as follows:

[0142] [ka]

[0143] (In the formula, the wavy line represents Q) 2 and R 6 It shows one of the structures selected from the groups represented by (indicating the bonding position with).

[0144] In one embodiment of the present invention, in formula (2) above, A is -O-, R 2 However, it is methyl, R 3 However, it is methyl, R 4 However, C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 However, halogen and C 1-3 A benzene ring or pyridine ring which may have one substituent selected from the group consisting of alkyl groups, L 1 However, it is a single bond, -O-, or -C(=O)-, and Ring Q 2 However, the benzene ring, C 4-7 Cycloalkane ring, or C 4-7 A compound or a pharmaceutically acceptable salt thereof, which is a cycloalkene ring, is provided.

[0145] In another embodiment of the present invention, in formula (2) above, n R 1 However, it is methoxy, and R 4 However, a compound or a pharmaceutically acceptable salt thereof is provided, which is 3,3,3-trifluoro-2,2-dimethylpropyl.

[0146] In another embodiment of the present invention, the compound represented by formula (2) or a pharmaceutically acceptable salt thereof is the compound represented by the following formula (2') or a pharmaceutically acceptable salt thereof. Therefore, in one embodiment of the present invention, the following formula (2'):

[0147] [ka]

[0148] [In the formula, A is -O- or -CF2-, R 1 may be substituted with halogens, or 1 to 3 halogens -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 A 4- to 6-membered heterocycloalkyl group having 2 alkyl atoms or one nitrogen atom as a ring member atom. R 2 and R 3 These are, independently, hydrogen or C 1-6 It is alkyl, R 4 C may be substituted with 1 to 3 halogens. 1-6 Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 A cycloalkylmethyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1is halogen and C 1-3 A benzene ring which may have one or two groups selected from the group consisting of alkyl groups, a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, L 1 These are single bonds, -O-, -CH2-, or -C(=O)-, Ring Q 2 This is a benzene ring which may be substituted with one halogen, C 4-7 A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. 4-7 A cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, B is -L 2 -L 3 -L 4 -R 6 And, L 2 C is a single bond. 1-6 Alkylene, -C(=O)-, -C(=O)NH-, -(CH2) k -C(=O)NH- (where k is an integer from 1 to 3), or -NHC(=O)-, L 3 C is a single bond. 1-6 Alkilen, C 3-6 The cycloalkylene is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, L 4 These are single bonds, -NH-, -N(-R 7 )-(R 7 is C 1-6 It is alkyl, -CH2-, or -C(=O)-, and R 6The provided compound is represented by [an E3 ligase binding moiety, autophagy-recruiting moiety, lysosome-recruiting moiety, kinase-recruiting moiety, phosphatase-recruiting moiety, glycosyltransferase-recruiting moiety, acetyltransferase-recruiting moiety, or ADC] or a pharmaceutically acceptable salt thereof.

[0149] Since formula (2') corresponds to a sub-concept of formula (2), the definitions, descriptions, preferred embodiments, etc., for each group in formula (2) above all apply to each group in formula (2'). Furthermore, in this specification, when "compound represented by formula (2)" is referred to without any particular reservation, this is a concept that also includes "compound represented by formula (2')", in other words, it means "compounds represented by formula (2) and formula (2')".

[0150] In one embodiment of the present invention, R in formulas (2) and (2') above 6 This is the E3 ligase binding portion, and in another embodiment of the present invention, R in formulas (2) and (2') above 6 This is the CRBN binding region. 6 For E3 ligase binding portions or CRBN binding portions that can be used as such, the references in <3. E3 ligase binding portions> above can be applied as is.

[0151] In another embodiment of the present invention, R in formulas (2) and (2') above 6 The formula is as follows:

[0152] [ka]

[0153] [In the formula, R 8 is hydrogen, or C 1-6 It is alkyl, W, X, Y, and Z are each independently a nitrogen atom, or a halogen, C 1-6 Alkyl and -OC 1-6A carbon atom which may have one group selected from the group consisting of alkyl groups, l, m, and n each independently represent an integer from 0 to 3, and The wavy line is L 4 It is one of the groups selected from [showing the bonding position with].

[0154] In yet another embodiment of the present invention, R in formulas (2) and (2') above 6 The formula is as follows:

[0155] [ka]

[0156] [In the formula, R 8 is hydrogen, or C 1-6 It is alkyl, V is a halogen, and The wavy line is L 4 It is one of the groups selected from [showing the bonding position with].

[0157] In one embodiment of the present invention, in formulas (2) and (2') above, R 1 However, it may be substituted with 1 to 3 halogens -OC 1-6 It is alkyl, R 4 However, C may be substituted with 1 to 3 halogens. 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 It is a cycloalkylmethyl, Ring Q 1 However, halogen and C 1-6 A benzene ring which may have one or two groups selected from the group consisting of alkyls, a 9 to 10-membered bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C 4-7 Cycloalkane ring, or C 4-7 It is a cycloalkene ring, and L 1However, compounds or pharmaceutically acceptable salts thereof are provided, which have single bonds or -O- bonds.

[0158] In one embodiment of the present invention, in formulas (2) and (2') above, A is -O-, R 2 However, it is methyl, and R 3 A compound or a pharmaceutically acceptable salt thereof, which is methyl, is provided.

[0159] In one embodiment of the present invention, in formulas (2) and (2') above, R 1 However, it is methoxy, and R 4 However, a compound or a pharmaceutically acceptable salt thereof is provided, which is 3,3,3-trifluoro-2,2-dimethylpropyl.

[0160] In one embodiment of the present invention, in formulas (2) and (2') above, Ring Q 1 However, it is a benzene ring which may have one halogen, L 1 However, it is a single bond, and Ring Q 2 However, compounds or pharmaceutically acceptable salts thereof that are cyclohexene rings are provided.

[0161] In another embodiment of the present invention, the following group: 3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione, (3R)-3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione, (3S)-3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl}piperidine-2,6-dione, 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3R)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3S)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, 3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3R)-3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, (3S)-3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}piperidine-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione, 3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione, (3R)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione, and (3S)-3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A compound selected from the above, or a pharmaceutically acceptable salt thereof, is provided. These compounds all correspond to the compound represented by formula (2) above, or a pharmaceutically acceptable salt thereof.

[0162] In another embodiment of the present invention, the compound represented by formula (2) or a pharmaceutically acceptable salt thereof may be its crystals. Accordingly, in one embodiment of the present invention, crystals of the compound represented by formula (2) or a pharmaceutically acceptable salt thereof are provided. These crystals can be produced by methods known to the present, or by methods described in the examples described later, or by similar methods.

[0163] Powder X-ray diffraction measurements of crystals can be performed using methods commonly used in this field, for example, by the method described in the examples below. Generally, the diffraction angle (2θ) in powder X-ray diffraction can vary within a range of approximately ±0.2°2θ. For example, the lattice constant of hydrates and dehydrated products changes due to the addition and removal of crystal water, which can also affect the diffraction angle (2θ) in powder X-ray diffraction. The intensity of the diffraction peak may also change due to differences in the crystal growth plane (crystal habit), etc. Therefore, when the crystals of the present invention are represented based on powder X-ray diffraction data, the scope of the present invention includes not only crystals whose peak diffraction angles and X-ray diffraction patterns match those of powder X-ray diffraction crystals, but also hydrates and dehydrated products obtained therefrom.

[0164] In one embodiment of the present invention, the crystal is (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione The benzenesulfonate crystals, obtained by irradiation with copper Kα rays (λ=1.54 angstroms), have peaks at diffraction angles (2θ) of 2.15±0.2, 8.30±0.2, 10.29±0.2, 14.75±0.2, 17.19±0.2, 20.00±0.2, 21.34±0.2, 22.68±0.2, 23.77±0.2, and 25.23±0.2.

[0165] In one embodiment of the present invention, the crystal is (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione The ethanesulfonate crystals, obtained by irradiation with copper Kα rays (λ=1.54 angstroms), have peaks at diffraction angles (2θ) of 2.21±0.2, 12.04±0.2, 14.87±0.2, 17.69±0.2, 18.93±0.2, 20.41±0.2, 22.42±0.2, 23.19±0.2, 24.13±0.2, and 27.98±0.2.

[0166] In one embodiment of the present invention, the crystal is (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione The 10-camphor sulfonate crystals, obtained by irradiation with copper Kα rays (λ=1.54 angstroms), have peaks at diffraction angles (2θ) of 3.89±0.2, 6.81±0.2, 7.68±0.2, 8.20±0.2, 10.28±0.2, 13.15±0.2, 15.97±0.2, 16.81±0.2, 18.58±0.2, and 23.56±0.2.

[0167] In one embodiment of the present invention, the crystal is (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione ethanesulfonic acid salt The material is a crystal having peaks at diffraction angles (2θ) of 2.27±0.2, 8.18±0.2, 9.88±0.2, 13.09±0.2, 14.57±0.2, 15.80±0.2, 16.91±0.2, 17.77±0.2, 18.87±0.2, and 20.14±0.2 in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ=1.54 angstroms).

[0168] In one embodiment of the present invention, the crystal is (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The salicylate crystals, obtained by irradiation with copper Kα rays (λ=1.54 angstroms), have peaks at diffraction angles (2θ) of 2.20±0.2, 4.34±0.2, 9.45±0.2, 10.97±0.2, 13.23±0.2, 16.98±0.2, 18.09±0.2, 20.20±0.2, 21.32±0.2, and 25.19±0.2.

[0169] In one embodiment of the present invention, the crystal is (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The benzenesulfonate crystals, obtained by irradiation with copper Kα rays (λ=1.54 angstroms), have peaks at diffraction angles (2θ) of 2.19±0.2, 8.87±0.2, 10.86±0.2, 12.55±0.2, 13.05±0.2, 14.99±0.2, 17.84±0.2, 20.62±0.2, 21.43±0.2, and 25.27±0.2.

[0170] In one embodiment of the present invention, the crystal is (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The 10-camphor sulfonate crystals, obtained by irradiation with copper Kα rays (λ=1.54 angstroms), have peaks at diffraction angles (2θ) of 2.20±0.2, 7.82±0.2, 11.05±0.2, 12.42±0.2, 13.34±0.2, 15.23±0.2, 16.49±0.2, 17.86±0.2, 20.15±0.2, and 24.36±0.2.

[0171] <7. Salts, isomers, prodrugs, etc.> In the present invention, "pharmaceutically acceptable salt" means a salt that can be used as a medicine. If the compound or polyfunctional molecule of the present invention has an acidic group, it can be reacted with a base to form a basic salt (also referred to as a "base addition salt"), and if it has a basic group, it can be reacted with an acid to form an acidic salt (also referred to as an "acid addition salt"). Therefore, in one embodiment of the present invention, the pharmaceutically acceptable salt of the compound represented by formula (1) or the compound represented by formula (2) is a basic salt, and in another embodiment of the present invention, the pharmaceutically acceptable salt of the compound represented by formula (1) or the compound represented by formula (2) is an acidic salt.

[0172] In the present invention, suitable examples of "basic salts" include alkali metal salts such as sodium salts, potassium salts, and lithium salts; alkaline earth metal salts such as magnesium salts and calcium salts; organic base salts such as N-methylmorpholine salt, triethylamine salt, tributylamine salt, diisopropylethylamine salt, dicyclohexylamine salt, N-methylpiperidine salt, pyridine salt, 4-pyrrolidinopyridine salt, and picoline salt; or amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate salt, and aspartate salt.

[0173] In the present invention, suitable examples of "acidic salts" include hydrohalides such as hydrofluoric acid, hydrochloride, hydrobromide, and hydroiodide; inorganic salts such as nitrates, perchlorates, sulfates, and phosphates; lower alkanesulfons such as methanesulfonates, trifluoromethanesulfons, and ethanesulfons; arylsulfons such as benzenesulfons and p-toluenesulfons; organic salts such as acetates, malates, fumarates, succinates, citrates, ascorbic acid, tartrates, oxalates, and maleates; or amino acid salts such as glycine salts, lysine salts, arginine salts, ornithine salts, glutamates, and aspartates.

[0174] The compounds of the present invention or their pharmaceutically acceptable salts may absorb water molecules and become hydrates when left in the air or recrystallized, and such hydrates are also included in the present invention. Furthermore, the compounds of the present invention or their pharmaceutically acceptable salts may absorb certain solvents and become solvates when left in a solvent or recrystallized, and such solvates are also included in the present invention. In addition, the compounds of the present invention or their pharmaceutically acceptable salts may exist as amorphous or crystalline substances.

[0175] Furthermore, the compounds of the present invention or their pharmaceutically acceptable salts may be labeled with one or more pharmaceutically acceptable radioactive or non-radioactive isotopes. Examples of isotopes that can be incorporated into the compounds of the present invention or their pharmaceutically acceptable salts include isotopes of hydrogen, carbon, nitrogen, oxygen, and fluorine, for example, respectively. 2 H, 3 H, 11 C, 13 C, 14 C, 13 N, 15 N, 15 O, 17 O, 18 O, and 18 F may be listed, but is not limited to these. Radioactive or non-radioactive labeled compounds may be useful in determining or measuring the efficacy of the compounds of the present invention by characterizing, for example, the site or mode of action, or the binding affinity to pharmacologically important sites of action. Such isotope-labeled compounds can be prepared by conventional techniques generally known to those skilled in the art.

[0176] The compounds of the present invention, their pharmaceutically acceptable salts, or their solvates may exist as various isomers depending on the type and combination of substituents, including geometric isomers such as cis and trans isomers, tautomers, rotational isomers, and optical isomers such as d and l isomers (including enantiomers and diastereomers). Unless otherwise specified, the compounds of the present invention include all of these isomers, stereoisomers, and mixtures of these isomers and stereoisomers in any ratio. These mixtures of isomers can be separated by known separation methods.

[0177] Furthermore, the present invention also includes prodrugs of compounds represented by formula (1) or formula (2). A prodrug is a compound having a group that can be converted to an amino group, hydroxyl group, carboxyl group, etc., by hydrolysis or under physiological conditions. Examples of groups that form such prodrugs include those described in Prog. Med., Vol. 5, pp. 2157-2161, 1985, etc. More specifically, such prodrugs include: (1) If an amino group is present in the compound, examples include compounds in which the amino group has been acylated, alkylated, or phosphorylated (for example, compounds in which the amino group has been eicosanoylated, alanylated, pentylaminocarbonylated, (5-methyl-2-oxo-1,3-dioxolene-4-yl)methoxycarbonylated, tetrahydrofuranylated, pyrrolidylmethylated, pivaloyloxymethylated, or tert-butylated). (2) If a hydroxyl group is present in the compound, examples include compounds in which the hydroxyl group has been acylated, alkylated, phosphorylated, or borated (for example, compounds in which the hydroxyl group has been acetylated, palmitoylated, propanoylated, pivaloylated, succinylated, fumalylated, alanylated, or dimethylaminomethylcarbonylated). (3) If a carboxyl group is present in the compound, examples include compounds in which the carboxyl group has been esterified or amidized (for example, compounds in which the carboxyl group has been ethyl esterified, phenyl esterified, carboxymethyl esterified, dimethylaminomethyl esterified, pivaloyloxymethyl esterified, ethoxycarbonyloxyethyl esterified, amidized, or methylamidized).

[0178] <8. Compositions and Pharmaceutical Uses> In one aspect of the present invention, a composition for inhibiting SF-1, a composition for inducing the degradation of SF-1, or a pharmaceutical composition is provided, containing the compound represented by formula (1) above or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a portion equivalent to the compound or a pharmaceutically acceptable salt thereof, or the compound represented by formula (2) above or a pharmaceutically acceptable salt thereof, or crystals thereof. In another aspect of the present invention, a method for treating a disease is provided, characterized by administering an effective amount of the compound represented by formula (1) above or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a portion equivalent to the compound or a pharmaceutically acceptable salt thereof, or the compound represented by formula (2) above or a pharmaceutically acceptable salt thereof, or crystals thereof, to a subject requiring treatment of the disease. Furthermore, in yet another aspect of the present invention, the compound represented by formula (1) above or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a portion equivalent to the compound or a pharmaceutically acceptable salt thereof, or the compound represented by formula (2) above or a pharmaceutically acceptable salt thereof, or crystals thereof, for use in the treatment of a disease is provided. In addition, in yet another embodiment of the present invention, a compound represented by formula (1) above or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a portion equivalent to said compound or a pharmaceutically acceptable salt thereof, or a compound represented by formula (2) above or a pharmaceutically acceptable salt thereof, or crystals thereof, are provided for the manufacture of a pharmaceutical for the treatment of a disease.

[0179] In the present invention, "composition for inhibiting SF-1" means a composition intended to inhibit SF-1. Inhibition of SF-1 typically means inhibiting the physiological activity of SF-1, and in particular, blocking or attenuating the expression of genes whose transcription is regulated by SF-1. Examples of SF-1 inhibition include blocking or attenuating the transcriptional induction activity of downstream genes by directly binding to SF-1, but also blocking or attenuating the physiological activity of SF-1 by acting on proteins upstream of SF-1 without directly binding to SF-1. "Composition for inhibiting SF-1" includes not only compositions whose sole purpose is SF-1 inhibition, but also those whose purpose includes SF-1 inhibition as one of its objectives. "Composition for inhibiting SF-1" typically refers to compositions in which SF-1 inhibition is listed as one of its uses in the accompanying documentation, packaging, or promotional materials, but also includes compositions that substantially include SF-1 inhibition as one of their uses even without such explicit mention.

[0180] In the present invention, "composition for inducing the decomposition of SF-1" means a composition intended to induce the decomposition of SF-1. "Composition for inducing the decomposition of SF-1" includes not only compositions whose sole purpose is to induce the decomposition of SF-1, but also compositions whose purpose includes the induction of SF-1 decomposition as one of its uses. Typically, "composition for inducing the decomposition of SF-1" refers to compositions in which the induction of SF-1 decomposition is listed as one of its uses in the accompanying documentation, packaging, promotional materials, etc., but also includes compositions that substantially include the induction of SF-1 decomposition as one of their uses even without such explicit mention.

[0181] In the present invention, "pharmaceutical composition" means a composition used for the treatment / prevention of any disease. Since the compounds or polyfunctional molecules of the present invention have SF-1 antagonist activity, they can be used as therapeutic and / or preventive compositions for diseases in which SF-1 is involved in the development or progression. Such diseases include, but are not limited to, castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer and other cancers, Cushing's syndrome, and primary aldosteronism. Therefore, in one aspect of the present invention, the pharmaceutical composition of the present invention is for the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer and other cancers, Cushing's syndrome, or primary aldosteronism. In a further aspect of the present invention, the pharmaceutical composition of the present invention is for the treatment of castration-resistant prostate cancer or adrenocortical carcinoma. In another aspect of the present invention, the pharmaceutical composition of the present invention is for the treatment of castration-resistant prostate cancer. In yet another aspect of the present invention, the pharmaceutical composition of the present invention is for the treatment of adrenocortical carcinoma.

[0182] The route of administration of such compositions to humans or other animals may be oral administration in the form of tablets, pills, capsules, granules, powders, liquids, etc., or parenteral administration in the form of injections for intra-articular, intravenous, intramuscular, etc., suppositories, eye drops, eye ointments, transdermal solutions, ointments, transdermal patches, transmucosal solutions, transmucosal patches, inhalants, etc. However, considering that the molecular weight of the compounds or polyfunctional molecules of the present invention is not extremely large, oral administration is preferred from the viewpoint of reducing the burden of taking medication.

[0183] Solid compositions for oral administration include tablets, powders, and granules. grainExamples include agents, etc. Such solid compositions contain, in addition to the compound or polyfunctional molecule of the present invention, at least one inert excipient, such as lactose, mannitol, glucose, hydroxypropyl cellulose, microcrystalline cellulose, starch, polyvinyl pyrolidone, magnesium aluminometasilicate, etc. Such solid compositions may also contain inert additives, such as lubricants such as magnesium stearate, disintegrants such as sodium carboxymethyl starch, stabilizers, solubilizers, etc., according to conventional methods. Tablets or pills may, if necessary, be coated with sugar or a film of gastric-soluble or enteric-soluble material.

[0184] Examples of liquid compositions for oral administration include pharmaceutically acceptable emulsifiers, solutions, suspensions, syrups, elixirs, etc. Such liquid compositions may contain commonly used inert diluents, such as purified water or ethanol. In addition to inert diluents, such liquid compositions may also contain auxiliary agents such as solubilizers and wetting agents, sweeteners, flavoring agents, fragrances, and preservatives.

[0185] Examples of injectable preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, and emulsions. Examples of aqueous solvents include distilled water for injection and physiological saline. Examples of non-aqueous solvents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, and polysorbate 80. Such injectable compositions may further contain isotonic agents, preservatives, wetting agents, emulsifiers, dispersants, stabilizers, solubilizers, etc. These injectable compositions can be sterilized, for example, by filtration through a bacteria-retaining filter, by adding a bactericide, or by irradiation. Alternatively, these injectable compositions can be prepared as sterile solid compositions and dissolved or suspended in sterile water or a sterile solvent for injection before use.

[0186] Examples of topical preparations include ointments, plasters, creams, gels, poultices, sprays, lotions, eye drops, and eye ointments. These topical preparations may contain commonly used ointment bases, lotion bases, aqueous or non-aqueous solutions, suspensions, emulsions, etc. For example, examples of ointment or lotion bases include polyethylene glycol, propylene glycol, white petrolatum, bleached beeswax, polyoxyethylene hydrogenated castor oil, glyceryl monostearate, stearyl alcohol, cetyl alcohol, lauromacrogol, and sorbitan sesquioleate.

[0187] Inhalants, nasal preparations, and other transmucosal preparations are used in solid, liquid, or semi-solid form and can be manufactured according to conventionally known methods. For example, known excipients, as well as pH adjusters, preservatives, surfactants, lubricants, stabilizers, thickeners, etc., may be added as appropriate. For these transmucosal preparations, a suitable inhalation or blowing device can be used as the method of administration. For example, known devices such as metered-dose inhalation devices. De Using a vise or sprayer, the compound or polyfunctional molecule can be administered alone or as a powder in a formulated mixture, or as a solution or suspension in combination with a pharmaceutically acceptable carrier. Dry powder inhalers, etc., may be for single or multiple doses, and can use dry powder or powder-containing capsules. Alternatively, a suitable excipient may be used. For example, it may be in the form of a pressurized aerosol spray using a suitable gas such as chlorofluoroalkane, hydrofluoroalkane, or carbon dioxide.

[0188] The composition of the present invention may contain other active ingredients, or may be used in combination with another composition containing other active ingredients. This combination may involve simultaneous administration, separate and consecutive administration, or administration at desired time intervals. The simultaneous administration formulation may be a combination formulation or formulated separately.

[0189] The amount of the compound or polyfunctional molecule of the present invention used to fill a composition, or the amount administered to a subject, is not particularly limited as long as it is an effective amount to achieve the objective, and can be appropriately selected according to the purpose of use, the subject's age, weight, symptoms, health condition, disease progression, etc. The frequency of administration is also not particularly limited and can be appropriately selected according to the purpose; for example, the daily dose may be administered once a day, or divided into multiple doses.

[0190] In this invention, "effective dose" or "therapeutic effective dose" means an amount effective in treating, preventing the progression of, or alleviating the existing symptoms of the subject being treated. The effective dose can be determined appropriately in accordance with conventional methods, taking into account the desired therapeutic effect and side effects.

[0191] <9. Combined Use> The compounds of the present invention or their pharmaceutically acceptable salts, polyfunctional molecules, compositions for inhibiting SF-1, compositions for inducing the degradation of SF-1, or pharmaceutical compositions may be used in combination with other antitumor agents. Examples of other antitumor agents include alkylating agents, antimetabolites, antitumor antibiotics, microtubule inhibitors, topoisomerase inhibitors, BRMs (biological response regulators), hormones, vitamins, antitumor antibodies, molecularly targeted drugs, and other antitumor agents.

[0192] More specifically, examples of alkylating agents include alkylating agents such as nitrogen mustard, nitrogen mustard-N-oxide, and chlorambutyl; aziridine alkylating agents such as carbocone and thiotepa; epoxide alkylating agents such as dibromomannitol and dibromodalcitol; nitrosourea alkylating agents such as carmustine, lomustine, semustine, nimustine hydrochloride, streptozosin, chlorozotosin, and ranimustine; busulfan; improsulfan tosylate; and dacarbazine.

[0193] Examples of various antimetabolites include purine antimetabolites such as 6-mercaptopurine, 6-thioguanine, and thioinosine; pyrimidine antimetabolites such as fluorouracil, tegafur, tegafur-uracil, carmofur, doxifluridine, proxuridine, cytarabine, enocitabine, and capecitabine; folic acid antimetabolites such as methotrexate, trimethrexate, and pemetrexed; and activated folic acid preparations such as levofolinate.

[0194] Examples of antitumor antibiotics include anthracycline antibiotics such as daunorubicin, acralubicin, doxorubicin, pirarubicin, THP-adriamycin, 4'-epidoxorubicin, epirubicin, and amrubicin; mitomycin C; bleomycin; peplomycin; chromomycin A3; and actinomycin D.

[0195] Examples of microtubule inhibitors include vinca alkaloids such as vindesine, vincristine, vinblastine, and vinorelbine; taxanes such as paclitaxel, docetaxel, and cabazitaxel; and eribulin.

[0196] Examples of topoisomerase inhibitors include epipodophyllotoxins such as etoposide and teniposide, and camptothecin derivatives such as irinotecan.

[0197] Examples of BRMs include tumor necrosis factor and indomethacin.

[0198] Examples of hormone preparations include hydrocortisone, cortisone acetate, fludrocortisone, fludrocortisone acetate, dexamethasone, methylprednisolone, prednisolone, prasterone, betamethasone, triamcinolone, oxymetholone, nandrolone, metenolone, phosphestrol, ethinylestradiol, chlormadinone, glucocorticoids, medroxyprogesterone, bicalutamide, enzalutamide, apalutamide, DaLorutamide, Flutamide, Anastrozole, Exemestane, Letrozole, Abiraterone, Goserelin, Leuprorelin, Toremifene, Degale Ri Examples include kus, mitotane, and tamoxifen.

[0199] Examples of vitamins include vitamin C and vitamin A.

[0200] Examples of antitumor antibodies and molecularly targeted drugs include antitumor antibodies such as trastuzumab, rituximab, cetuximab, pertuzumab, nimotuzumab, pembrolizumab, camrelizumab, denosumab, bevacizumab, infliximab, and ramucirumab (including their modified forms); kinase inhibitors such as imatinib, gefitinib, erlotinib, sunitinib, lapatinib, eganerisib, sorafenib, dasatinib, nilotinib, vemurafenib, osimertinib, apatinib, and cabozantinib; PARP inhibitors such as olaparib, rucaparib, velparib, and niraparib; and molecularly targeted drugs such as OR-449.

[0201] Other antitumor agents include, for example, platinum compounds such as cisplatin, carboplatin, and oxaliplatin, ifosfamide, cyclophosphamide, melphalan, L-asparaginase, acegraton, schizophyllan, picibanil, procarbazine, pipobromane, neocartinostatin, hydroxyurea, ubenimex, and krestin.

[0202] Furthermore, the compounds of the present invention or their pharmaceutically acceptable salts, polyfunctional molecules, compositions for inhibiting SF-1, compositions for inducing the degradation of SF-1, or pharmaceutical compositions may be used in combination with antibody-drug conjugates (ADCs) containing the above-mentioned other antitumor agents as a payload, or with target protein degradation inducers that use the above-mentioned other antitumor agents as POI ligands.

[0203] The compounds of the present invention or pharmaceutically acceptable salts thereof, polyfunctional molecules, compositions for inhibiting SF-1, compositions for inducing the degradation of SF-1, or pharmaceutical compositions may be administered simultaneously or separately with the above-mentioned concomitant agents, and may be provided as combination or kit formulations.

[0204] Examples of antitumor agents suitably used in combination with the compounds of the present invention or their pharmaceutically acceptable salts, polyfunctional molecules, compositions for inhibiting SF-1, compositions for inducing the degradation of SF-1, or pharmaceutical compositions in the treatment of adrenocortical carcinoma include anthracycline compounds such as doxorubicin; platinum compounds such as cisplatin and carboplatin; antitumor antibodies such as nivolumab, pembrolizumab, and camrelizumab; molecularly targeted drugs such as eganerisib, apatinib, cabozantinib, and OR-449; mitotane; and etoposide, one or more of these.

[0205] In the treatment of castration-resistant prostate cancer, the compounds of the present invention or their pharmaceutically acceptable salts, polyfunctional molecules, compositions for inhibiting SF-1, compositions for inducing the degradation of SF-1, or antitumor agents suitably used in combination with pharmaceutical compositions include abiraterone, enzalutamide, Da Examples include one or more selected from hormonal agents such as lorutamide and apalutamide; microtubule inhibitors such as docetaxel and cabazitaxel; PARP inhibitors such as olaparib and rucaparib; androgen receptor degradation inducers such as ARV-110, ARV-766, and CC-94676; CYP11A1 enzyme inhibitors such as ODM-208; and antitumor antibodies such as nivolumab, pembrolizumab, and camrelizumab.

[0206] <10. Novel Intermediates> In one embodiment of the present invention, the following formula (10):

[0207] [ka]

[0208] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -and, Here, R a is hydrogen or C 1-3 It is alkyl, R b and R c These are, independently, hydrogen, halogen, or C 1-3 It is alkyl, and The alkyl group is either unsubstituted or substituted with 1 to 3 halogens. n R 1 These are, independently, halogen, hydroxyl, -CN, and C. 1-6 Alkyl, C 2-6 Alkenyl, -OC 1-6 Alkyl, -N(H)-C 1-3 Alkyl, -N(C 1-3 Alkyl)2, C 3-7 Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 2 and R 3 These are, independently, hydrogen, halogen, and C. 1-6 Alkyl, or C 2-6 It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R 4 C 1-6Alkyl, -C(=O)-R d (R d C 1-6 Alkyl, C 2-5 Alkenil, C 3-7 (representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C 6-12 It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C 1-6 Alkyl is either unsubstituted or has 1 to 3 halogens, C 3-7 Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q 1 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 A cycloalkene ring, or a heterocycloalkene ring with 3 to 7 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L 1These are single bonds, -O-, -S-, -NH-, and C 1-3 Alkilen, C 2-3 Alkenylenes are -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-. Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q 2 C 6-12 Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C 3-7 Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C 5-12 The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or halogenated, unsubstituted C 1-3 Alkyl and C 1-3 It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R 10 C 1-6 It is alkyl, Here, Said C 1-6 The alkyl group is substituted with one or two 3- to 7-membered heterocycloalkyl groups. The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, and The heterocycloalkyl group is either unsubstituted or substituted with an amino group protecting group, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof is provided.

[0209] The compound of formula (10) of the present invention can be used as a manufacturing intermediate for the compound of formula (2) or formula (2') of the present invention, or is useful as such, as detailed in the following general manufacturing methods and examples. The compound of formula (10) of the present invention is R 10 Except for the difference in definition from the compound of formula (1), it is identical to the compound of formula (1). Therefore, the definitions, explanations, preferred embodiments, etc. for each group in the above formula (1) are as follows: 5 Except for those relating to the above, all of these also apply to each of the groups in equation (10).

[0210] In one embodiment of the present invention, R in formula (10) 10 C is substituted with one 3- to 7-membered heterocycloalkyl group. 1-6 C is alkyl (the heterocycloalkyl is either unsubstituted or substituted with an amino group protecting group), preferably substituted with one 4- to 6-membered heterocycloalkyl group. 1-6 The C is alkyl (the heterocycloalkyl is either unsubstituted or substituted with an amino group protecting group), and more preferably substituted with one 6-membered heterocycloalkyl. 1-6 C is alkyl (the heterocycloalkyl is either unsubstituted or substituted with an amino group protecting group), and is particularly preferably substituted with piperazine. 1-6 Alkyl (the Piperazine (These are either unsubstituted or substituted with an amino group protecting group.)

[0211] In one embodiment of the present invention, "amino group protecting group" means a protecting group used as an amino group protecting group in the synthesis of organic compounds, for example, alkoxycarbonyl groups such as tert-butoxycarbonyl group, methoxycarbonyl group, ethoxycarbonyl group, 2,2,2-trichloroethoxycarbonyl group, 2-trimethylsilylethoxycarbonyl group; allyloxycarbonyl group; arylmethoxycarbonyl groups such as benzyloxycarbonyl group, 4-methoxybenzyloxycarbonyl group, 4-nitrobenzyloxycarbonyl group, 2-nitrobenzyloxycarbonyl group; 9-f Examples of protecting groups for amino groups include the ruorenylmethyloxycarbonyl group; arylmethyl groups such as benzyl group, 4-methoxybenzyl group, 2,3-dimethoxybenzyl group, 3,4-dimethoxybenzyl group, diphenylmethyl group, and triphenylmethyl group; alkanoyl groups such as formyl group, acetyl group, trimethylacetyl group, trichloroacetyl group, and trifluoroacetyl group; alloyl groups such as benzoyl group; or arylsulfonyl groups such as benzenesulfonyl group, p-toluenesulfonyl group, 2-nitrobenzenesulfonyl group, 4-nitrobenzenesulfonyl group, and 2,4-dinitrobenzenesulfonyl group. These amino group protecting groups can be selected according to the properties of the compound protecting the amino group, and the removal of these protecting groups can be carried out by selecting reagents and conditions appropriate to the protecting group.

[0212] <11.General manufacturing method> The following describes typical methods for producing the compounds of the present invention or their pharmaceutically acceptable salts. The compounds of the present invention can be produced by various manufacturing methods, and the manufacturing methods shown below, as well as the reference examples and examples described later, are merely examples and should not be interpreted as limiting the present invention to these. Each starting compound may form a salt, provided that it does not inhibit the reaction. Examples of such salts are the same as the pharmaceutically acceptable salts of the aforementioned compounds. Unless otherwise specified, the raw material compounds can be readily obtained and used as commercially available products, or they can be manufactured according to known methods or similar methods. Furthermore, the manufacturing intermediates produced in the following manufacturing methods may be isolated and purified by methods such as column chromatography (including normal-phase and reverse-phase) using silica gel, alumina, etc., recrystallization, reprecipitation, and distillation, or they may be used directly in the next reaction without isolation or purification. In this specification, all patent, non-patent, or reference materials expressly cited may be incorporated herein by reference as part of this specification. Compounds, their pharmaceutically acceptable salts, and their manufacturing intermediates can be produced by applying various known manufacturing methods, taking advantage of their characteristics based on their basic skeleton or the type of substituents. Known methods include, for example, those described in "ORGANIC FUNCTIONAL GROUP PREPARATIONS," 2nd edition, ACADEMIC PRESS, INC., 1989, and "Comprehensive Organic Transformations," 2nd edition, VCH Publishers Inc., 1999. In such cases, depending on the type of functional group present in the compound, it may be technically effective in the manufacturing process to protect the functional group with an appropriate protecting group at the raw material or intermediate stage, or to replace it with a group that can be easily converted to that functional group. Examples of such functional groups include amino groups, hydroxyl groups, formyl groups, carbonyl groups, and carboxyl groups, and examples of their protecting groups include those described in "Protective Groups in Organic Synthesis," 5th edition, Wiley, 2014, by PG Wuts. Protecting groups, or groups that can be easily converted to such functional groups, may be appropriately selected and used according to the respective reaction conditions of the manufacturing method for producing the compound. According to this method, after introducing the group and carrying out the reaction, the protecting group can be removed or converted to the desired group as needed to obtain the desired compound. Prodrugs of compounds can be produced by introducing a specific group at the raw material or intermediate stage, similar to the protecting groups described above, or by carrying out a reaction using the resulting compound. Reactions for producing prodrugs can be carried out by applying methods known to those skilled in the art, such as ordinary esterification, amidation, dehydration, and hydrogenation. Furthermore, the functional group transformation and the use of protecting groups in the manufacturing intermediates used in each step of the method described below can be carried out by known methods or similar methods, or by the methods described in the examples below or similar methods. In the following description of general manufacturing methods, symbols used in formulas without a defined definition have the same meaning as those described above.

[0213] The following describes a general method for preparing the compound of formula (1) of the present invention. The abbreviations shown herein may be used in the following description. THF: Tetrahydrofuran DMF: N,N-dimethylformamide DMA: N,N-dimethylacetamide HATU:1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate DIPEA: N,N-diisopropylethylamine RuPhos Pd G3: (2-Dicyclohexylphosphino-2',6'-Diisopropyloxy-1,1'-biphenyl)[2-(2'-Amino-1,1'-biphenyl)] Palladium(II) Methanesulfonate (CAS Registry Number: 1445085-77-7) BrettPhos Pd G3:[(2-di-cyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II ) Tansulfonate (CAS Registry Number: 1470372-59-8) Tf: Trifluoromethanesulfonyl group SEM: 2-(trimethylsilyl)ethoxymethyl group XantPhos:4,5-bis(diphenylphosphin)-9,9-dimethylxanthene (CAS Registry Number: 161265-03-8) tBuXPhos:2-di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl (CAS Registry Number: 564483-19-8)

[0214] (Method A) Among the compounds represented by formula (1), R 4 However, C may be substituted with 1 to 3 halogen atoms. 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 Compound a12, R, which has a cycloalkylmethyl group 4 However, C may be substituted with 1 to 3 halogen atoms. 1-6 Compound a11, which is an alkylcarbonyl group, and R 4 However, compound a14, which is a six-membered heteroaryl group having one or two nitrogen atoms as ring member atoms (the heteroaryl group may be substituted with one halogen atom), can be produced according to the following method. The general production methods for each reaction site are shown in order, but each step does not necessarily have to be carried out in the order shown below, as long as it does not affect the reaction substrate and reaction product.

[0215] [ka]

[0216] [wherein, Pg 1 These are protecting groups for carboxyl groups (e.g., methyl group, ethyl group, benzyl group, or tert-butyl group, etc.), M is a metal or a metal halide (for example, magnesium halide, lithium halide, or zinc halide, etc.). R a1 C may be substituted with 1 to 3 halogen atoms. 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6It is a cycloalkyl group, R a2 The formula is as follows:

[0217] [ka]

[0218] A substituent represented by, R X R 5 , or R 5 It is a base that can be converted to, R a3 This is a six-membered heteroaryl group having one or two nitrogen atoms as ring member atoms (the heteroaryl group may be substituted with one halogen atom).

[0219] The first step is to obtain compound a3 by an aldol condensation reaction of compound a1 and compound a2. The aldol condensation reaction in this step can be carried out, for example, by reacting compound a1 and compound a2 using acetic acid and piperidine as catalysts.

[0220] The second step involves obtaining compound a5 by 1,4-nucleophilic addition of compound a4 to the α,β-unsaturated ester of compound a3. The 1,4-nucleophilic addition reaction in this step can be carried out, for example, by reacting compound a3 and compound a4 in a solvent such as THF and in the presence of a copper reagent such as copper(II) bromide. The reaction temperature is preferably between -78°C and room temperature.

[0221] The third step involves obtaining compound a6 by hydrolysis of the ester of compound a5 and decarboxylation of the resulting carboxyl group. The hydrolysis and decarboxylation reactions in this step can be carried out, for example, by reacting compound a5 with a base such as sodium hydroxide in a solvent such as ethylene glycol under heating.

[0222] The fourth step is to obtain compound a7 by reducing the cyano group of compound a6. The reduction reaction in this step can be carried out, for example, by reacting compound a6 with a reducing agent such as lithium aluminum hydride in a solvent such as THF under heating.

[0223] The fifth step is to obtain compound a9 from compound a7 and compound a8 by a reductive amination reaction. The reductive amination reaction in this step can be carried out, for example, by reacting compound a7 and compound a8 with a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride in a solvent such as dichloromethane or methanol. It is preferable to add an acid such as acetic acid in this reaction. Alternatively, the reductive amination reaction in this step can also be carried out, for example, by using a Dean-Stark apparatus to react compound a7 with compound a8 in a solvent such as toluene, heating the resulting imine, and then reacting it with a reducing agent such as sodium borohydride in a solvent such as methanol.

[0224] The sixth step is to condense compound a9 and compound a10 to obtain compound a11. The condensation reaction in this step can be carried out, for example, by reacting compound a9 and compound a10 with a condensing agent such as HATU in a solvent such as DMF. Alternatively, the condensation reaction in this step can also be carried out by reacting an acid chloride obtained by reacting compound a10 with oxalyl chloride, etc., in a solvent such as dichloromethane, and then reacting the resulting acid chloride with compound a9 in a solvent such as dichloromethane, in the presence of a base such as DIPEA.

[0225] The seventh step is to obtain compound a12 by reducing the carbonyl group of compound a11. The reduction reaction in this step can be carried out, for example, by reacting compound a11 with a reducing agent such as a borane-THF complex in a solvent such as THF under heating.

[0226] The eighth step is to obtain compound a14 from compound a9 and compound a13 by a Buchwald amination reaction or an aromatic nucleophilic substitution reaction. The Buchwald amination reaction in this step can be carried out by reacting compound a9 with compound a13 under heating in a solvent such as 1,4-dioxane, in the presence of a base such as cesium carbonate and a metal catalyst such as RuPhos Pd G3 or BrettPhos Pd G3. The aromatic nucleophilic substitution reaction in this step can be carried out by reacting compound a9 with compound a13 under heating in a solvent such as 2-butanol or N,N-dimethylacetamide, in the presence of a base such as 1,8-diazabicyclo[5.4.0]-7-undecene or potassium carbonate.

[0227] R 5 However, the following formula:

[0228] [ka]

[0229] In the case of a group represented by R, 5 The parts can be introduced according to known methods. Examples of such known methods include, but are not limited to, WO 2013088315 A1 and WO 2020192588 A1.

[0230] R 5 However, the following formula:

[0231] [ka]

[0232] In the case of a group represented by R, 5 The site can be introduced according to known methods. Examples of such known methods include, but are not limited to, J. Org. Chem., 2000, 65, 1, 169-175 and Tetrahedron Lett., 1998, 39, 5731-5734.

[0233] R 5 However, the following formula:

[0234] [ka]

[0235] In the case of a group represented by R, 5 The site can be introduced according to known methods. Examples of such known methods include, but are not limited to, J. Org. Chem., 2015, 80, 6391-6399 and WO 2019148132 A1.

[0236] (B method) Of the compounds represented by formula (1), the compound represented by formula b2 below can be produced according to the following method.

[0237] [ka]

[0238] [In the formula, R b1 is a single bond, or a hydroxyl group, C 1-6 C may have a group selected from the group consisting of an alkoxy group, a piperazinyl group, and a 1-tert-butoxycarbonylpiperazinyl group. 1-6 It is an alkylene group, Pg 1 It is a protecting group for the carboxyl group.

[0239] The first step is protecting the carboxyl group with Pg 1 This is a step to obtain compound b2 from compound b1 by a deprotection reaction. The deprotection reaction in this reaction can be carried out by a method commonly used for deprotecting protecting groups of carboxyl groups. For example, Pg 1 However, in the case of a methyl group or an ethyl group, this can be carried out by reacting compound b1 with a base such as an aqueous sodium hydroxide solution in a solvent such as methanol.

[0240] (C method) Of the compounds represented by formula (1), the compounds represented by formulas c2 and c5 below can be produced according to the following method.

[0241] [ka]

[0242] [In the formula, R c1 This is a single bond, or a carboxyl group, a hydroxyl group and C 1-6 C may have substituents selected from the group consisting of alkoxy groups. 1-6 It is an alkylene group, Pg 1 It is a protecting group for the carboxyl group, and Pg 2 X is a protecting group for amino groups, c [This is a leaving group.]

[0243] The first step is to obtain compound c2 by reducing the ester of compound c1. The reduction reaction in this step can be carried out, for example, by reacting compound c1 with a reducing agent such as lithium aluminum hydride or diisobutylaluminum hydride in a solvent such as THF.

[0244] The second step involves converting the hydroxyl group of compound c2 into a leaving group to obtain compound c3. Examples of leaving groups in this step include methanesulfonyloxy group and p-toluenesulfonyloxy group, which can be converted using commonly used methods (reagents, solvents, reaction conditions, etc.).

[0245] The third step is to obtain compound c5 from compound c3 and compound c4 by a nucleophilic substitution reaction. The nucleophilic substitution reaction in this step can be carried out by reacting compound c3 with compound c4 under heating in a solvent such as DMF or acetonitrile, and / or can also be carried out in the presence of a base such as N,N-diisopropylethylamine.

[0246] The fourth step is to protect the amino group of compound c5 with Pg 2This step involves deprotecting to obtain compound c6. The deprotection reaction in this step can be carried out by a method commonly used for deprotecting protecting groups of amino groups. For example, Pg 2 However, in the case of the tert-butoxycarbonyl group, this can be carried out by reacting compound C5 with an acid such as hydrogen chloride or trifluoroacetic acid in a solvent such as dichloromethane.

[0247] (D method) Of the compounds represented by formula (1), the compounds represented by formula d5 or d7 below can be produced according to the following manufacturing method.

[0248] [ka]

[0249] [wherein, Pg 3 These are protecting groups for hydroxyl groups (e.g., methyl group, benzyl group, methoxymethyl group, etc.), Lg is a leaving group, R d1 The formula is as follows:

[0250] [ka]

[0251] A group represented by, or a group that can be converted to said group, R d2 C 1-3 Alkylamino group, diC 1-3 An alkylamino group, or a 4- to 6-membered saturated heterocyclic group having one nitrogen atom as a ring member atom, R d3 C may be substituted with 1 to 3 halogen atoms. 1-6 It is an alkyl group.

[0252] The first step is protecting the hydroxyl group with Pg 3This step involves obtaining compound d2 from compound d1 through a deprotection reaction. The deprotection reaction in this step can be carried out by a method commonly used for deprotecting hydroxyl group protecting groups. For example, Pg 3 However, in the case of a methyl group, the reaction can be carried out by reacting compound d1 with sodium thiomethoxide under heating in a solvent such as DMF. This reaction can also be carried out under microwave irradiation. The reaction temperature is preferably 80°C to 160°C.

[0253] The second step is to obtain compound d3 from compound d2 by triflatation of the hydroxyl group. The triflatation reaction in this step can be carried out, for example, by reacting compound d2 with a triflatating agent such as trifluoromethanesulfonic anhydride in a solvent such as dichloromethane and in the presence of a base such as pyridine.

[0254] The third step is to obtain compound d5 from compound d3 and amine d4 by a Buchwald amination reaction. In this step, the Buchwald amination reaction can be carried out by reacting compound d3 and amine d4 under heating in a solvent such as 1,4-dioxane, in the presence of a ligand such as 2-(di-tert-butylphosphinone)biphenyl and a metal catalyst such as tris(dibenzylideneacetone)dipalladium(0).

[0255] The fourth step is to obtain compound d7 by an alkylation reaction between compound d2 and alkylating agent d6. The alkylation reaction in this step can be carried out, for example, by reacting alkylating agent d6 and compound d2 under heating in a solvent such as DMF and in the presence of a base such as potassium carbonate. The reaction temperature is preferably from room temperature to 150°C.

[0256] (Law E) Among the compounds represented by formula (1), L 1 Compound e4, which is -C(=O)-, can be prepared according to the following method.

[0257] [ka]

[0258] [In the formula, R is given by the following formula:

[0259] [ka]

[0260] It is a base represented by, M is a dihydroxyboryl group, a pinacolateboryl group, etc. R X R 5 Or, R 5 It is a base that can be converted to [this].

[0261] The first step is to convert carboxylic acid e1 to acid chloride e2. In this step, the chlorination reaction can be carried out, for example, by reacting compound e1 with a chlorinating agent such as oxalyl chloride or thionyl chloride in a solvent such as dichloromethane in the presence of a catalytic amount of DMF.

[0262] The second step involves obtaining compound e4 by a coupling reaction between compound e2 and compound e3. This coupling reaction can be carried out, for example, by reacting compound e2 and compound e3 under heating in a solvent such as toluene, in the presence of a base such as cesium carbonate, and a metal catalyst such as tetrakis(triphenylphosphine)palladium(O). An example of literature describing this coupling reaction is found in Catalysts, 2019, 9(1), 53.

[0263] Next, equation (3):

[0264] [ka]

[0265] [In the formula, R X R 5 , or R 5It is a base that can be converted to [ The method for producing the raw material compound represented by is shown.

[0266] (F method) Of the raw material compounds (3), L 1 However, the oxygen atom is compound f3, L 1 However, compound f6, which has a single bond, and Q 1 However, compounds f12 and f13, which are 7-azaspiro[3.5]nonane rings, can be prepared according to the following method.

[0267] [ka]

[0268] [In the formula, R f1a , R f1b , R f1c , and R f1d Each of these is independently a hydrogen atom, a halogen atom, or C 1-6 It is an alkyl group, R f2 R is an OH group or a leaving group, where R f2 However, in the case of OH, R f3 is an OH group, or a leaving group, or R f2 However, in the case of a leaving group, R f3 OH is, Y 1 Y is a halogen atom, a trifluoromethanesulfonyloxy group, a pinacolate boryl group, or a dihydroxyboryl group, where Y 1 However, in the case of a halogen atom or a trifluoromethanesulfonyloxy group, Y 2 is a pinacolate boryl group or a dihydroxyboryl group, or Y 1 However, in the case of a pinacolate boryl group or a dihydroxyboryl group, Y 2 This is a halogen atom or a trifluoromethanesulfonyloxy group. Pg 1 is a protecting group for the carboxyl group, and R X R 5 , or R 5It is a base that can be converted to [this].

[0269] The first step is to obtain compound f3 from compound f1 and compound f2. f2 However, it is OH and R f3 However, if it is OH, this reaction can be carried out by the Mitsunobu reaction. The Mitsunobu reaction in this step can be carried out, for example, by reacting compound f1 and compound f2 with a phosphine such as triphenylphosphine and an azodicarboxylic acid ester such as diisopropyl azodicarboxylic acid in a solvent such as THF. Also, R f2 or R f3 However, in the case of a leaving group, this reaction can be carried out by a nucleophilic substitution reaction. The nucleophilic substitution reaction in this step can be carried out, for example, by reacting compound f1 and compound f2 with a base such as potassium carbonate or cesium carbonate under heating in a solvent such as DMF or N,N-dimethylacetamide.

[0270] The second step is to obtain compound f6 by a coupling reaction between compound f4 and compound f5. The coupling reaction in this step can be carried out by heating compound f4 and compound f5 in a solvent such as aqueous 1,4-dioxane, a base such as potassium carbonate, and a metal catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct.

[0271] The third step is to obtain compounds f9 and f10 by the Mitsunobu reaction between compound f7 and compound f8. The Mitsunobu reaction in this step can be carried out, for example, by reacting compounds f7 and f8 with a phosphorane reagent such as cyanomethylenetributylphosphorane under heating in a solvent such as toluene.

[0272] The fourth step is to obtain compound f11 by the reduction reaction of compound f9. The reduction reaction in this step can be carried out under the same conditions as the first step of method C.

[0273] The fifth step is to obtain compound f12 from compound f11 by an oxidation reaction. The oxidation reaction in this step can be carried out, for example, by reacting compound f11 with an oxidizing agent such as 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one or manganese(IV) oxide in a solvent such as dichloromethane.

[0274] Furthermore, compound f13 can be obtained by applying the same steps as the fourth and fifth steps of this method to compound f10.

[0275] The following describes a general method for producing the compound of formula (2) of the present invention.

[0276] (G method) Method G is a method for producing the compound represented by formula (2).

[0277] [ka]

[0278] [In the formula, R 6’ The formula is as follows:

[0279] [ka]

[0280] It is one of the groups selected from the groups represented by R 6’’ These are protecting groups of imides (e.g., (2-trimethylsilylethoxy)methyl group, tert-butoxycarbonyl group, benzyloxymethyl group, etc.), Q 3 The formula is as follows:

[0281] [ka]

[0282] It is one of the bases selected from, Pg 1 These are protecting groups for carboxyl groups (e.g., methyl group, ethyl group, tert-butyl group, etc.).

[0283] R 6’ However, the following formula:

[0284] [ka]

[0285] If the group is represented by , this step can be carried out by deprotecting the protecting group of compound (4).

[0286] The deprotection reaction in this step can be carried out by a method commonly used for deprotecting the protecting group of the nitrogen atom of an imide. For example, if the protecting group is an SEM group, the deprotection reaction in this step can be carried out by reacting compound (4) with an acid such as trifluoroacetic acid in a dichloromethane solvent to remove the trimethylsilylethyl group, and then reacting it with a base such as N,N'-dimethylethylenediamine in a solvent such as ethyl acetate.

[0287] R 6’ However, the following formula:

[0288] [ka]

[0289] If the group is one of those selected from, this step can be carried out by a cyclization reaction.

[0290] The cyclization reaction in this process is Pg 1 However, in the case of a tert-butyl group, the reaction can be carried out, for example, by reacting compound (4) with an acid such as benzenesulfonic acid under heating in a solvent such as acetonitrile. Furthermore, the cyclization reaction in this step is Pg 1However, if it is a methyl group or an ethyl group, this can be carried out, for example, by reacting compound (4) with a base such as tert-butoxy potassium in a solvent such as THF.

[0291] R 6’ However, the following formula:

[0292] [ka]

[0293] If the group is represented by , this step can be carried out by a catalytic hydrogen reduction reaction.

[0294] The catalytic hydrogen reduction reaction in this process can be carried out, for example, by reacting compound (4) with a metal catalyst such as palladium-carbon in a solvent such as ethyl acetate or ethanol under a hydrogen atmosphere.

[0295] Next, equation (4):

[0296] [ka]

[0297] The method for producing the raw material compound represented by is shown.

[0298] (H method) Of the raw material compounds (4), L 4 However, compound h4, which is -C(=O)-, can be produced according to the following method.

[0299] [ka]

[0300] [In the formula, R 1 , R 2 , R 3 , R 4 , R 6’ , ring Q 1 , ring Q 2, ring Q 3 , L 1 , and L 2 is synonymous with the above, and L 3 is a piperazinediyl group, a piperazine-2-onediyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediy group, and X h is a halogen atom.]

[0301] The first step is a step of converting compound h1 into compound h2 by a carbonylation reaction. The carbonylation reaction in this step can be carried out, for example, by reacting compound h1 with 2,4,6-trichlorophenyl formate (CAS registration number: 4525-65-9) under heating in a solvent such as toluene, in the presence of a base such as triethylamine, a ligand such as XantPhos, and a metal catalyst such as palladium(II) acetate in a carbon monoxide atmosphere.

[0302] The second step is a step of obtaining compound h4 from compound h2 and compound h3 by an amidation reaction. The amidation reaction in this step can be carried out, for example, by reacting compound h2 and compound h3 under heating in a solvent such as acetonitrile, in the presence of a base such as DIPEA, and a catalyst such as 4-dimethylaminopyridine.

[0303] (Method I) Among the starting compounds (4), compound i4 in which L 4 is -CH2- can be produced according to the following method.

[0304] [Chemical formula]

[0305] [In the formula, R 1 , R 2 , R 3 , R 4 , R 6’ , ring Q 1 , ring Q 2 , ring Q 3 , L 1, and L 2 is synonymous with the above, and L 3 is a piperazinediyl group, a piperazine-2-onediyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediy group, and X i is a halogen atom.]

[0306] The first step is a step of converting compound i1 into compound i2 by a formylation reaction. The formylation reaction in this step can be carried out, for example, by reacting compound i1 with a reducing agent such as triethylsilane under heating in a solvent such as toluene, in the presence of a base such as triethylamine, a ligand such as XantPhos, and a metal catalyst such as palladium(II) acetate in a carbon monoxide atmosphere. In this reaction, it may be preferable to add saccharin.

[0307] The second step is a step of obtaining compound i4 from compound i2 and compound i3 by a reductive amination reaction. The reductive amination reaction in this step can be carried out, for example, by reacting compound i2 and compound i3 with a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride in a solvent such as dichloromethane or methanol. In this reaction, it may be preferable to add an acid such as acetic acid. Further, the reductive amination reaction in this step can also be carried out, for example, by reacting a reducing agent such as sodium borohydride in a solvent such as methanol with an imine obtained by reacting compound i3 and compound i2 under heating in a solvent such as toluene using a Dean-Stark apparatus.

[0308] (J method) Among the starting compounds (4), compound j3 in which L 2 is C=O can be produced according to the following method.

[0309] [Chemical formula]

[0310] [In the formula, R 1 , R 2 , R 3 , R 4 , R 6’ , ring Q 1 , ring Q 2 , ring Q 3 , L 1 , and L 4 This is synonymous with the above, L 3 This group is a piperazinediyl group, a piperazine-2-ondiyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediyl group.

[0311] The first step involves condensing compound j1 and compound j2 to obtain compound j3. This condensation reaction can be carried out, for example, by reacting compound j1 and compound j2 with a condensing agent such as HATU in a solvent such as DMF. Alternatively, this condensation reaction can also be carried out by reacting compound j1 with a chlorinating agent such as oxalyl chloride in a solvent such as dichloromethane in the presence of a catalytic amount of DMF, obtaining an acid chloride, and then reacting that acid chloride with compound j2 in a solvent such as dichloromethane in the presence of a base such as DIPEA.

[0312] L 2 However, CONH, or (CH2) n Compounds of the form CONH (where n is an integer from 1 to 3) can be obtained under similar conditions by changing compound j1 and compound j2 to their corresponding carboxylic acids and amines, respectively.

[0313] L 2 However, the NHCO compound can be obtained under similar conditions by changing compound j1 and compound j2 to the corresponding amine and carboxylic acid, respectively.

[0314] (K method) Of the raw material compounds (4), L 2 However, compound k3, which is -CH2-, can be produced according to the following method.

[0315] [ka]

[0316] [In the formula, R 1 , R 2 , R 3 , R 4 , R 6’ , ring Q 1 , ring Q 2 , ring Q 3 , L 1 , and L 4 This is synonymous with the above, L 3 This group is a piperazinediyl group, a piperazine-2-ondiyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediyl group.

[0317] The first step involves obtaining compound k3 from compound k1 and compound k2 by a reductive amination reaction. The reductive amination reaction in this step can be carried out under the same conditions as the second step of Method I.

[0318] L 2 However, C 2-6 Compounds containing alkylene groups can also be obtained under similar conditions by changing compound k1 to the corresponding aldehyde.

[0319] (L method) Of the raw material compounds (4), Q 2 However, it is a benzene ring which may be substituted with one halogen atom, L 2 However, compound l6, which is -NHCO-, can be produced according to the following method.

[0320] [ka]

[0321] [where, X l It is a halogen atom, Pg 2It is a protecting group for amino groups, R l1 The formula is as follows:

[0322] [ka]

[0323] It is a base represented by, R l2a , R l2b , R l2c , and R l2d Each of these is independently a hydrogen atom or a halogen atom, and R l3 The formula is as follows:

[0324] [ka]

[0325] This refers to a group represented by [this symbol], or a group that can be converted to said group.

[0326] The first step is to obtain compound l3 from compound l1 and compound l2 by a Buchwald amination reaction. The amination reaction in this step can be carried out by reacting compound l1 and compound l2 under heating in a solvent such as tert-butyl alcohol or DMSO, with a ligand such as 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphin)ferrocene or tBuXPhos; a metal catalyst such as tris(dibenzylideneacetone)dipalladium(0); and a base such as cesium carbonate or 7-methyl-1,5,7-triazabicyclo[4.4.0]deca-5-ene.

[0327] The second step is protecting the amino group with Pg 2 This step involves converting compound l3 to compound l4 through a deprotection reaction. The deprotection reaction in this step can be carried out by a method commonly used for deprotecting the protecting group of an amino group. For example, Pg 2However, if it is a tert-butoxycarbonyl group, this can be carried out by reacting compound l3 with an acid such as hydrochloric acid in a solvent such as dichloromethane.

[0328] The third step involves obtaining compound l6 through a condensation reaction between compound l4 and compound l5. This condensation reaction can be carried out under the same conditions as the first step of the J method.

[0329] The fourth step is to obtain compound l6 from compound l4 and compound l7 by a urea formation reaction. In this step, the urea formation reaction can be carried out by reacting compound l4 with triphosgene in a solvent such as dichloromethane and in the presence of a base such as triethylamine or pyridine to obtain carbamoyl chloride, and then reacting the resulting carbamoyl chloride with compound l7 in a solvent such as dichloromethane and in the presence of a base such as triethylamine.

[0330] Next, equation (5):

[0331] [ka]

[0332] [In the formula, R X The formula is as follows:

[0333] [ka]

[0334] It is a base that can be converted to the base represented by [the symbol]. The method for producing the raw material compound represented by is shown.

[0335] Of the raw material compounds (5), L 2 However, C=O, CONH, (CH2) n Compounds that are CONH (where n is an integer from 1 to 3) or NHCO can be produced by a method similar to the J method. Of the raw material compounds (5), L 2 However, C 1-6Compounds containing alkylene groups can be produced by a method similar to the K method.

[0336] (M method) Of the raw material compounds (5), L 2 However, C 1-6 Compound m5, which is an alkylene group, can be produced according to the following method.

[0337] [ka]

[0338] [In the formula, L 3 This is a piperazinediyl group, a piperazine-2-ondiyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediyl group. Lg is a leaving group (for example, a bromine atom, an iodine atom, a chlorine atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, a trifluoromethanesulfonyloxy group, etc.), R m1 The formula is as follows:

[0339] [ka]

[0340] (In the formula, n is an integer from 0 to 5.) It is a base represented by, Pg 1 It is a protecting group for the carboxyl group, R X The formula is as follows:

[0341] [ka]

[0342] It is a base that can be converted to the base represented by [the symbol].

[0343] The first step is to obtain compound m2 by reducing the ester group of compound m1. The reduction reaction in this step can be carried out, for example, by reacting compound m1 with a reducing agent such as lithium aluminum hydride or diisobutylaluminum hydride in a solvent such as tetrahydrofuran.

[0344] The second step is to convert the hydroxyl group of compound m2 into a leaving group to obtain compound m3. Examples of leaving groups in this step include bromine atoms, iodine atoms, chlorine atoms, methanesulfonyloxy groups, p-toluenesulfonyloxy groups, and trifluoromethanesulfonyloxy groups, and the conversion to a leaving group can be carried out by commonly used methods (reagents, solvents, reaction conditions, etc.).

[0345] The third step involves obtaining compound m5 from compound m3 and compound m4 by a nucleophilic substitution reaction. This nucleophilic substitution reaction can be carried out by reacting compound m3 and compound m4 under heating in a solvent such as DMF or acetonitrile. In this reaction, it is sometimes preferable to add a base such as N,N-diisopropylethylamine.

[0346] Next, equation (6):

[0347] [ka]

[0348] [In the formula, R y The formula is as follows:

[0349] [ka]

[0350] It is a group that can be converted to the group represented by [this symbol]. The method for producing the raw material compound represented by is shown.

[0351] The starting compound (6) is either publicly known or produced using a known compound as a starting material according to a known or similar method. The known compound can be purchased from a commercial supplier or can be readily synthesized by methods described in the literature or similar methods. Examples of publicly known literature include, but are not limited to, WO2022081928 A1, WO2022081927 A1, WO2019060693 A1, WO2019038717 A1, ACS Med. Chem. Lett., 2021, 12, 1733, and WO2021170109 A1.

[0352] The following describes the N method to the P method as examples of preparation methods for raw material compound (6), but the synthesis methods for raw material compound (6) are not limited to these.

[0353] (N method) Of the raw material compounds (6), Q 3 However, the following formula:

[0354] [ka]

[0355] Compound n8, which is one of the groups selected from the following, can be prepared according to the method described below.

[0356] [ka]

[0357] [In the formula, Y 1 It is a halogen atom, Y 2 These are halogen atoms, dihydroxyboryl groups, or pinacolateboryl groups, etc. R n1a and R n1b These are, independently, a hydrogen atom or a halogen atom. Pg 2 is a protecting group for amino groups, and n is an integer of 1 or 2.

[0358] The first step is a reaction to convert compound n1 into compound n2 by a halogenation reaction. The halogenation reaction in this step can be carried out, for example, by reacting compound n1 with a halogenating agent such as N-bromosuccinimide, benzyltrimethylammonium tribromide, N-iodosuccinimide, etc. in a solvent such as DMF.

[0359] The second step is a step to obtain compound n4 by ureidating compound n2 using compound n3. The ureidation reaction in this step can be carried out, for example, by reacting compound n2 with compound n3 in a solvent such as dichloromethane in the presence of a base such as DIPEA.

[0360] The third step is a step to obtain compound n5 by the cyclization reaction of compound n4. The cyclization reaction in this step can be carried out, for example, by reacting compound n4 with a copper catalyst such as copper(I) iodide under heating in a solvent such as DMSO in the presence of a copper ligand such as trans-4-hydroxy-L-proline and a base such as tripotassium phosphate. The reaction temperature is preferably from 80 °C to 160 °C.

[0361] The fourth step is a step to obtain compound n7 from compound n5 and compound n6. 2 When Y is a halogen atom, this step can be carried out by an alkylation reaction. The alkylation reaction in this step can be carried out, for example, by reacting compound n5 with compound n6 in a solvent such as DMF in the presence of a base such as potassium carbonate, cesium carbonate, etc. 2 When Y is a pinacolato boryl group or the like, this step can be carried out by a Chan-Lam-Evans coupling reaction. The Chan-Lam-Evans coupling reaction in this step can be carried out, for example, by reacting compound n5 with compound n6 under heating in an organic solvent such as acetonitrile in the presence of a base such as triethylamine and a metal catalyst such as copper(II) acetate.

[0362] The fifth step is protecting the amino group with Pg 2 This step involves converting compound n7 to compound n8 through a deprotection reaction. The deprotection reaction in this step can be carried out by a method commonly used for deprotecting the protecting group of an amino group.

[0363] (O method) Of the raw material compounds (6), Q 3 However, the following formula:

[0364] [ka]

[0365] Compound o4, which is one of the groups selected from the following, can be prepared according to the method described below.

[0366] [ka]

[0367] [In the formula, A 1 , A 2 , and A 3 These are, independently, carbon atoms or nitrogen atoms, X o These are halogen atoms, or pinacolate boryl groups, etc. Y 1 is a nitro group or a halogen atom, R o1 R 8 , or R 6’ And, R o4 R 8 , or R 6’ And, A 1 However, when it is a nitrogen atom, R o2 It does not exist, A 1 However, when it is a carbon atom, R o2 is a hydrogen atom, or a halogen atom, or R o1 and R o2These are combined with each other to form the following equation:

[0368] [ka]

[0369] (In the formula, the lower end of the substructure is R o2 The joint is R o1 It may form any substructure selected from the group represented by (which is a combination of), A 2 However, when it is a nitrogen atom, R o3 It does not exist, A 2 However, when it is a carbon atom, R o3 is a hydrogen atom or a halogen atom, A 3 However, when it is a nitrogen atom, R o4 It does not exist, A 3 However, when it is a carbon atom, R o4 This is a hydrogen atom or a halogen atom.

[0370] Compounds o1 and o2 are either known or can be produced by using known compounds as starting materials and combining known or similar methods as appropriate. Examples of known methods include, but are not limited to, Bioorg. Med. Chem., 2013, 21, 125, J. Med. Chem., 1995, 38, 5, 771-793, WO2011163355 A1, WO2005044793 A2, WO2007015877 A2, WO2021213929 A1, WO2018039384 A1, and WO2016097749 A1.

[0371] The first step involves obtaining compound o2 by nitrating or halogenating compound o1. The nitration reaction in this step can be carried out, for example, by reacting compound o1 with a nitrating agent such as potassium nitrite in an acidic solvent such as trifluoroacetic acid. The halogenation reaction in this step can be carried out under the same conditions as the first step of the N method.

[0372] The second step involves obtaining compound o4 from compound o2 and compound o3 by an alkylation reaction or a Chan-Lam-Evans coupling reaction. The alkylation or Chan-Lam-Evans coupling reaction in this step can be carried out under the same conditions as the fourth step of the N method.

[0373] (P method) Of the raw material compounds (6), Q 3 However, the following formula:

[0374] [ka]

[0375] Compound p5, which is one of the groups selected from the following, can be prepared according to the method described below.

[0376] [ka]

[0377] [In the formula, A 1 is CH, or a nitrogen atom, A 2 It is CH2 or NH, X p It is a halogen atom, R p1 , R p2 , and R p3 These are, independently, either a hydrogen atom or a halogen atom.

[0378] The first step is to obtain compound p2 by nuclear reduction of compound p1. The nuclear reduction reaction in this step can be carried out, for example, by reacting compound p1 with a reducing agent such as 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate diethyl in a solvent such as dichloroethane, in the presence of an acid such as boronic acid or p-toluenesulfonic acid, under heating.

[0379] The second step involves obtaining compound p4 from compounds p2 and p3 by urea conversion. The urea conversion reaction in this step can be carried out under the same conditions as the fourth step of the L method.

[0380] The third step involves obtaining compound p5 by a cyclization reaction of compound p4. The cyclization reaction in this step can be carried out under the same conditions as the third step in the N method. The reaction temperature is preferably from room temperature to 100°C.

[0381] Next, equation (7):

[0382] [ka]

[0383] [In the formula, R x’ The formula is as follows:

[0384] [ka]

[0385] This shows a method for producing a raw material compound represented by [a group that can be converted to a group represented by ].

[0386] (Q method) Of the raw material compounds (7), R 4 However, C may be substituted with 1 to 3 halogen atoms. 1-6 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 Compound q12, R is a cycloalkylmethyl group. 4However, C may be substituted with 1 to 3 halogen atoms. 1-6 Compound q11, which is an alkylcarbonyl group, and R 4 However, compound q14, which is a six-membered heteroaryl group having one or two nitrogen atoms as ring member atoms (the heteroaryl group may be substituted with one halogen atom), can be produced according to the following method. The general production methods for each reaction site are shown in order, but each step does not necessarily have to be carried out in the order shown below, as long as it does not affect the reaction substrate and reaction product.

[0387] [ka]

[0388] [wherein, Pg 1 It is a protecting group for the carboxyl group, M is a metal or a metal halide (e.g., magnesium halide, lithium halide, zinc halide, etc.). R q1 C may be substituted with hydrogen atoms and 1 to 3 halogen atoms. 1-5 C may be substituted with an alkyl group or one trifluoromethyl group. 3-6 It is a cycloalkyl group, R q2 The formula is as follows:

[0389] [ka]

[0390] It is a base represented by, R q3 This is a six-membered heteroaryl group having one or two nitrogen atoms as ring member atoms (the heteroaryl group may be substituted with one halogen atom).

[0391] The first step is to obtain compound q3 by an aldol condensation reaction of compound q1 and compound q2. In this step, the aldol condensation reaction can be carried out by reacting compound q1 and compound q2 using acetic acid and piperidine as catalysts, for example.

[0392] The second step involves obtaining compound q5 by 1,4-nucleophilic addition of compound q4 to the α,β-unsaturated ester of compound q3. The 1,4-nucleophilic addition reaction in this step can be carried out, for example, by reacting compound q3 and compound q4 in a solvent such as THF and in the presence of a copper reagent such as copper(II) bromide. The reaction temperature is preferably between -78°C and room temperature.

[0393] The third step involves obtaining compound q6 by hydrolysis of the ester group of compound q5 and decarboxylation of the resulting carboxyl group. The hydrolysis and decarboxylation reactions in this step can be carried out, for example, by reacting compound q5 with a base such as sodium hydroxide in a solvent such as ethylene glycol under heating.

[0394] The fourth step is to obtain compound q7 by reducing the cyano group of compound q6. The reduction reaction in this step can be carried out, for example, by reacting compound q7 with a reducing agent such as lithium aluminum hydride in a solvent such as THF under heating.

[0395] The fifth step is to obtain compound q9 from compounds q7 and q8 by a reductive amination reaction. The reductive amination reaction in this step can be carried out under the same conditions as the second step of Method I.

[0396] The sixth step involves condensing compound q9 and compound q10 to obtain compound q11. The condensation reaction in this step can be carried out under the same conditions as the first step of the J method.

[0397] The seventh step is to obtain compound q12 by reducing the carbonyl group of compound q11. The reduction reaction in this step can be carried out, for example, by reacting compound q11 with a reducing agent such as a borane-THF complex in a solvent such as THF under heating.

[0398] The eighth step is to obtain compound q14 from compound q9 and compound q13 by a Buchwald amination reaction or an aromatic nucleophilic substitution reaction. The Buchwald amination reaction in this step can be carried out by reacting compound q9 with compound q13 under heating in a solvent such as 1,4-dioxane, in the presence of a base such as cesium carbonate and a metal catalyst such as RuPhos Pd G3 or BrettPhos Pd G3. The aromatic nucleophilic substitution reaction in this step can be carried out by reacting compound q9 with compound q13 under heating in a solvent such as 2-butanol or N,N-dimethylacetamide, in the presence of a base such as 1,8-diazabicyclo[5.4.0]-7-undecene or potassium carbonate.

[0399] (R method) Among the compounds represented by formula (7), L 1 However, compound r4, which is -C(=O)-, can be produced according to the following method.

[0400] [ka]

[0401] [In the formula, R is given by the following formula:

[0402] [ka]

[0403] It is a base represented by, M is a dihydroxyboryl group, a pinacolate boryl group, etc.

[0404] The first step is to convert the carboxylic acid r1 into an acid chloride r2. The chlorination reaction in this step can be carried out, for example, by reacting compound r1 with a chlorinating agent such as oxalyl chloride or thionyl chloride in a solvent such as dichloromethane in the presence of DMF.

[0405] The second step involves obtaining compound r4 through a coupling reaction between compound r2 and compound r3. This coupling reaction can be carried out, for example, by reacting compound r2 with compound r3 under heating in a solvent such as toluene, a base such as cesium carbonate, and a metal catalyst such as tetrakis(triphenylphosphine)palladium(O). For reference, see Catalysts 2019, 9(1), 53.

[0406] (S method) In the compound represented by formula (7), R 1 The parts can be manufactured according to the following methods.

[0407] [ka]

[0408] [wherein, Pg 3 These are protecting groups for hydroxyl groups (e.g., methyl group, benzyl group, methoxymethyl group, etc.), Lg is a leaving group, R a The formula is as follows:

[0409] [ka]

[0410] A group represented by, or a group that can be converted to a group represented by said formula, R b C 1-3 Alkylamino group, diC 1-3An alkylamino group, or a 4- to 6-membered saturated heterocyclic group having one nitrogen atom as a ring member atom, R c C may be substituted with 1 to 3 halogen atoms. 1-6 It is an alkyl group.

[0411] The first step is protecting the hydroxyl group with Pg 3 This step involves obtaining compound s2 from compound s1 through a deprotection reaction. The deprotection reaction in this step can be carried out by a method commonly used for deprotecting hydroxyl group protecting groups. For example, Pg 3 However, if it is a methyl group, the reaction can be carried out by reacting compound s1 with sodium thiomethoxide under heating in a solvent such as DMF. This reaction can also be carried out under microwave irradiation. The reaction temperature is preferably 80°C to 160°C.

[0412] The second step is to obtain compound s3 by triflatation of the hydroxyl group of compound s2. The triflatation reaction in this step can be carried out, for example, by reacting compound s2 with a triflating agent such as trifluoromethanesulfonic anhydride in a solvent such as dichloromethane and in the presence of a base such as pyridine.

[0413] The third step is to obtain compound s5 from compound s3 and amine s4 by a Buchwald amination reaction. In this step, the Buchwald amination reaction can be carried out by reacting compound s3 with amine s4 under heating in a solvent such as 1,4-dioxane, a ligand such as 2-(di-tert-butylphosphinone)biphenyl, and a metal catalyst such as tris(dibenzylideneacetone)dipalladium(0).

[0414] The fourth step is to obtain compound s7 from compound s2 by an alkylation reaction using alkylating agent s6. The alkylation reaction in this step can be carried out, for example, by reacting compound s2 with alkylating agent s6 such as an alkyl halide in a solvent such as DMF, in the presence of a base such as potassium carbonate, and under heating. The reaction temperature is preferably from room temperature to 150°C.

[0415] Next, equation (8):

[0416] [ka]

[0417] [In the formula, R y’ The formula is as follows:

[0418] [ka]

[0419] This is a group that can be converted to the group represented by [ ]. A method for producing the raw material compound represented by [ ] is shown.

[0420] Of the starting compound (8), the following formula:

[0421] [ka]

[0422] As shown in L 4 However, compounds that are -C(=O)- can be produced by a method similar to the H method.

[0423] Of the starting compound (8), the following formula:

[0424] [ka]

[0425] As shown in L 4However, compounds that are CH2 can be produced by the same method as in Method I.

[0426] (T method) Of the raw material compounds (8), L 4 However, compound t6 is NH, and L 4 However, NR 9 (R 9 C 1-6 Compound t8, which exhibits an alkyl group, can be prepared according to the following method.

[0427] [ka]

[0428] [where, X t Pg is a halogen atom. 2 It is a protecting group for amino groups.

[0429] The first step is to obtain compound t2 from compound t1 by a reduction reaction of the nitro group. The reduction reaction in this step can be carried out by reacting compound t1 with a metal catalyst such as palladium-carbon in a solvent such as ethanol or THF under a hydrogen atmosphere.

[0430] The second step involves obtaining compound t4 from compound t3 by a Buchwald amination reaction. The amination reaction in this step can be carried out under the same conditions as the first step of the L method.

[0431] The third step is protecting the amino group of compound t4 with Pg 2 This step involves obtaining compound t2 through a deprotection reaction. The deprotection reaction in this step can be carried out by a method commonly used for deprotecting the protecting group of an amino group. For example, Pg 2 However, if it is a tert-butoxycarbonyl group, this can be carried out by reacting compound t4 with an acid such as hydrochloric acid in a solvent such as dichloromethane.

[0432] The fourth step is to obtain compound t6 from compound t2 and compound t5 by a reductive amination reaction. The reductive amination reaction in this step can be carried out under the same conditions as the second step of Method I. Alternatively, the reductive amination reaction in this step can also be carried out by reacting compound t2 and compound t5 with a reducing agent such as a borane-THF complex in a solvent such as THF.

[0433] The fifth step is to obtain compound t8 from compound t6 and compound t7 by a reductive amination reaction. The reductive amination reaction in this step can be carried out under the same conditions as in the fourth step of this method.

[0434] Next, equation (9):

[0435] [ka]

[0436] The method for producing the raw material compound represented by is shown.

[0437] (U Law) Of the raw material compounds (9), L 1 However, the compound u3, L is an oxygen atom. 1 However, compound u6, which has a single bond, and Q 1 However, compounds u12 and u13, which are 7-azaspiro[3.5]nonane rings, can be prepared according to the following methods, respectively.

[0438] [ka]

[0439] [In the formula, R u1a , R u1b , R u1c , and R u1d Each of these is independently a hydrogen atom, a halogen atom, or C 1-6 It is an alkyl group, R u2 R is a hydroxyl group or a leaving group (where Ru2 However, if it is a hydroxyl group, R u3 is a hydroxyl group or a leaving group, or R u2 However, if it is a leaving group, R u3 (is a hydroxyl group), Y 1 is a halogen atom, a trifluoromethanesulfonyloxy group, a pinacolate boryl group, or a dihydroxyboryl group (where Y 1 However, if it is a halogen atom or a trifluoromethanesulfonyloxy group, Y 2 is a pinacolate boryl group or a dihydroxyboryl group, or Y 1 However, if it is a pinacolate boryl group or a dihydroxyboryl group, Y 2 (This is a halogen atom or a trifluoromethanesulfonyloxy group), R x’ The formula is as follows:

[0440] [ka]

[0441] It is a group that can be converted to a group represented by, and Pg 1 It is a protecting group for the carboxyl group.

[0442] The first step is to obtain compound u3 from compound u1 and compound u2. u2 However, it is a hydroxyl group, and R u3 However, if it is a hydroxyl group, this reaction can be carried out by the Mitsunobu reaction. The Mitsunobu reaction in this step can be carried out, for example, by reacting compound u1 and compound u2 with a phosphine such as triphenylphosphine and an azodicarboxylic acid ester such as diisopropyl azodicarboxylic acid in a solvent such as tetrahydrofuran. u2 , or R u3If either of the groups is a leaving group, this reaction can be carried out by a nucleophilic substitution reaction. The nucleophilic substitution reaction in this step can be carried out, for example, by reacting compound u1 and compound u2 with a base such as potassium carbonate or cesium carbonate in a solvent such as DMF or DMA under heating.

[0443] The second step is to obtain compound u6 by a coupling reaction between compound u4 and compound u5. The coupling reaction in this step can be carried out by heating compound u4 and compound u5 in a solvent such as aqueous 1,4-dioxane, a base such as potassium carbonate, and a metal catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct.

[0444] The third step is to obtain compounds u9 and u10 from compounds u7 and u8 by the Mitsunobu reaction. The Mitsunobu reaction in this step can be carried out, for example, by reacting compounds u7 and u8 with a phosphorane reagent such as cyanomethylenetributylphosphorane under heating in a solvent such as toluene.

[0445] The fourth step involves obtaining compound u11 through the reduction reaction of compound u9. The reduction reaction in this step can be carried out under the same conditions as the first step of the M method.

[0446] The fifth step is to obtain compound u12 by an oxidation reaction of compound u11. The oxidation reaction in this step can be carried out, for example, by reacting compound u11 with an oxidizing agent such as 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3-(1H)-one or manganese(IV) oxide in a solvent such as dichloromethane.

[0447] Furthermore, compound u13 can be obtained by applying the same steps as in the fourth and fifth steps of this method to compound u10.

[0448] <12. Activity> In one embodiment of the present invention, the compound or polyfunctional molecule according to the present invention specifically binds to SF-1. The binding activity to SF-1 can be measured using any known method, for example, by reacting a test substance, a molecule known to specifically bind to SF-1 (particularly the SF-1 ligand-binding region (LBD)) (e.g., DAX1 peptide), and SF-1 (particularly SF-1-LBD), and quantifying the decrease in the binding rate to SF-1 by the molecule known to specifically bind to SF-1 (e.g., IC2). 50 It can be measured (by calculating the value). Generally, in such a test system, IC 50 Test substances with an IC50 value of 100 μM or less are considered to bind specifically to SF-1. Therefore, in one embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has an IC50 value of 100 μM or less, which is used to reduce the binding rate to SF-1 by molecules known to bind specifically to SF-1 (e.g., DAX1 peptide). 50 IC has a value, preferably 10 μM or less. 50 ICs having a value of 1 μM or less are particularly preferred. 50 It has a value. In another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention, in the test system and test conditions disclosed in Test Example 1 herein, has an IC of 100 μM or less with respect to the reduction in binding rate to SF-1-LBD by DAX1 peptide. 50 IC has a value, preferably 10 μM or less. 50 ICs having a value of 1 μM or less are particularly preferred. 50 It has a value.

[0449] In one aspect of the present invention, the compound or polyfunctional molecule according to the present invention has SF-1 antagonist activity. SF-1 antagonist activity can be measured using any known method, for example, by adding a test substance to cells expressing SF-1, culturing them for a certain period of time, and then quantifying the decrease in the expression levels of SF-1 target genes (e.g., CYP11A1, CYP17A1, CYP21A2, STAR, etc.) (e.g., IC 50It can be measured (by calculating the value). Generally, in such a test system, IC for SF-1 target genes 50 Test substances with an IC50 value of 100 μM or less are considered to have antagonist activity against SF-1. Therefore, in one embodiment of the present invention, the compound or polyfunctional molecule according to the present invention exhibits IC50 value of 100 μM or less against the target genes of SF-1 (e.g., CYP11A1, CYP17A1, CYP21A2 and / or STAR). 50 IC has a value, preferably 10 μM or less. 50 ICs having a value of 1 μM or less are particularly preferred. 50 It has a value. In another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has an IC of 100 μM or less relative to CYP11A1, CYP17A1, CYP21A2 and / or STAR in the test system and test conditions disclosed in Test Example 2 herein. 50 IC has a value, preferably 10 μM or less. 50 ICs having a value of 1 μM or less are particularly preferred. 50 It has a value.

[0450] In one aspect of the present invention, the compound or polyfunctional molecule according to the present invention has SF-1 degradation-inducing activity. SF-1 degradation-inducing activity can be measured using any known method, for example, by adding the test substance to cells expressing SF-1, culturing them for a certain period of time, and then quantifying the expression level of SF-1. SF-1 degradation-inducing activity can also be measured, for example, by knocking in an easily detectable peptide tag (e.g., a HiBiT tag) into the endogenous SF-1 gene locus in cells expressing SF-1, adding the test substance to the cells, culturing them for a certain period of time, and then observing the expression level of the peptide tag. Generally, in such a test system, a concentration (DC) that induces 50% degradation of SF-1 is used. 50 Test substances with a DC (D1) value of 100 μM or less are considered to have SF-1 degradation-inducing activity. Therefore, in one embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has a DC of 100 μM or less relative to SF-1. 50 Having a value, preferably DC of 10 μM or less.50 Having a value, and particularly preferably a DC of 1 μM or less. 50 It has a value. In another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has a DC of 100 μM or less relative to SF-1 in the test system and test conditions disclosed in Test Example 3 herein. 50 Having a value, preferably DC of 10 μM or less. 50 Having a value, and particularly preferably a DC of 1 μM or less. 50 It has a value.

[0451] In one embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has growth inhibitory activity against tumors in which SF-1 is involved in the development and progression; in another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has growth inhibitory activity against adrenocortical carcinoma; and in yet another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has growth inhibitory activity against NCI-H295R cells, which are adrenocortical carcinoma cell lines. The growth inhibitory activity against tumor cells can be measured using any known method, typically by adding the test substance to model cells of the target tumor, culturing them for a certain period of time, and then quantifying the growth rate of the tumor cells. Generally, in such a test system, a concentration (GI) that inhibits tumor cell proliferation by 50% is used. 50 Test substances with a GI value of 100 μM or less are considered to have growth inhibitory activity. Therefore, in one embodiment of the present invention, the compound or polyfunctional molecule according to the present invention is considered to have growth inhibitory activity against tumor cells (e.g., NCI-H295R cells) at a GI value of 100 μM or less. 50 Having a value, preferably GI of 10 μM or less. 50 Having a value, and particularly preferably a GI of 1 μM or less. 50 It has a value. In another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has a GI of 100 μM or less against tumor cells (e.g., NCI-H295R cells) in the test system and test conditions disclosed in Test Example 4 herein. 50 Having a value, preferably GI of 10 μM or less. 50 Having a value, and particularly preferably a GI of 1 μM or less. 50 It has a value.

[0452] In one aspect of the present invention, the compound or polyfunctional molecule according to the present invention has antitumor activity against tumor cells in which SF-1 is involved in its development and progression, such as NCI-H295R cells, an adrenocortical cancer cell line, or VCaP cells, a prostate cancer cell line, or an animal model (e.g., mouse) subcutaneously transplanted with tumors derived from prostate cancer patients. The antitumor activity in the transplantation model can be measured using any known method, for example, by protocols such as those described in Test Examples 5 and 6 of this specification. Furthermore, the therapeutic effect of the compound or polyfunctional molecule according to the present invention against breast cancer can be measured, for example, by protocols such as those described in Test Example 7 of this specification. [Examples]

[0453] The present invention will be described in detail by the following embodiments, but these are merely embodiments and do not limit the present invention, and may be modified without departing from the scope of the present invention. In the following examples, "%" indicates mol / mol% for yield, volume% for solvents used in chromatography, and weight% for others. Nuclear magnetic resonance spectrum (hereinafter 1 For 1H-NMR (resonance frequency 400 MHz or 500 MHz), tetramethylsilane was used as the standard substance, or the chemical shift value of the deuterated solvent used was used as the reference value, and the chemical shift value was expressed as a δ value (ppm). Other abbreviations used in the text have the following meanings. s: singlet d: doublet dd: Doublet of Doublets t: triplet dt: Doublet of Triplets q: quartet m: multiplet br: broad J: Coupling constant Hz: Hertz CDCl3: Deuterated chloroform DMSO-d6: Deuterated Dimethyl Sulfoxide CD3OD: Heavy methanol 1H-NMR: Proton Nuclear Magnetic Resonance HPLC: High-Performance Liquid Chromatography SFC: Supercritical Fluid Chromatography sCO2: Supercritical carbon dioxide APCI: Atmospheric pressure chemical ionization ESI: Electrospray Ionization THF: Tetrahydrofuran DMF: N,N-dimethylformamide HATU: 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate DIPEA: N,N-diisopropylethylamine RuPhos Pd G3: (2-dicyclohexylphosphino-2',6'-diisopropyloxy-1,1'-biphenyl) [2-(2'-amino-1,1'-biphenyl)] palladium(II) methanesulfonate BrettPhos Pd G3:[(2-di-cyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II ) Tansulfonate (S)-(-)-Tol-BINAP:(S)-(-)-2,2'-bis(di-p-trilphosphino)-1,1'-binaphthyl XantPhos:4,5-bis(diphenylphosphin)-9,9-dimethylxanthene (CAS Registry Number: 161265-03-8) IPA: Isopropyl alcohol DCM: Dichloromethane DMSO: Dimethyl sulfoxide TLC: Thin-layer chromatography

[0454] Also, in the following examples, formula:

[0455] [ka]

[0456] The structure shown indicates that the chiral carbon in the structure is a mixture of α-configuration and β-configuration.

[0457] Unless otherwise specified, the reagents, solvents, and equipment used in the following examples are commercially available. Furthermore, unless otherwise specified, the starting compounds are known compounds, commercially available, or synthesized and identified according to known or equivalent methods.

[0458] <Example A1> Ethyl cyano(2,2-dimethyltetrahydro-4H-pyran-4-ylidene)acetate 2,2-dimethyltetrahydro-4H-pyran-4-one (CAS registry number: 1194-16-7) (200 g, 1.56 mol) was cooled on ice and ethyl cyanoethyl (175 mL, 1.65 mol) was added dropwise over 10 minutes, followed by acetic acid (18 mL, 0.32 mol) over 5 minutes, and then piperidine (31 mL, 0.31 mol) over 10 minutes. The reaction mixture was brought to room temperature and stirred for 41 hours. The reaction mixture was diluted with ethyl acetate (2 L) and washed sequentially with 1 mol / L sodium hydroxide aqueous solution (1.5 L), water (1.5 L), and saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and further dried under reduced pressure to obtain the marked compound (324 g, 1.45 mol, yield 93%).

[0459] <Example A2> [4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl](cyano)ethyl acetate The compound obtained in Example A1 and 4-chlorophenylmagnesium bromide (CAS registry number: 873-77-8) were used to obtain the marked compound in the same manner as in Example C3.

[0460] <Example A3> 2-[4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine The compound obtained in Example A2 was used, and the same procedure as in Example C4 and Example C5 was followed in order to obtain the compound described above.

[0461] <Example A4> Ethyl trans-4-(4-formylphenoxy)cyclohexanecarboxylate To a solution of 4-hydroxybenzaldehyde (CAS registry number: 123-08-0) (10.0 g, 81.9 mmol), ethyl cis-4-hydroxycyclohexanecarboxylate (WO 2011143645 A1) (14.8 g, 86.0 mmol), and tri-n-butylphosphine (24.5 mL, 98.3 mmol) in toluene (400 mL), 1,1'-(azodicarbonyl)dipiperidine (24.8 g, 98.3 mmol) was gradually added at room temperature, and the mixture was stirred at room temperature for 1 hour and at 95°C for 3 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (600 mL), and washed sequentially with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The precipitated solid was filtered off and washed with a hexane / ethyl acetate (1 / 1) mixed solvent. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the labeled compound (5.94 g, 21.5 mmol, 26% yield).

[0462] <Example A5> Ethyl trans-4-{4-[({2-[4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexanecarboxylate The compounds obtained in <Example A4> and <Example A3> were used to obtain the labeled compound in the same manner as in <Example D1>.

[0463] <Example A6> Trans-4-(4-{[{2-[4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(2,2-dimethylpropanoyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid The compound obtained in Example A5 was used, and the same procedure as in Example D2 and Example S4 was followed in order to obtain the labeled compound.

[0464] <Example B1> Ethyl cyano{2,2-dimethyl-4-[4-(trifluoromethoxy)phenyl]tetrahydro-2H-pyran-4-yl}acetate The compound obtained in Example A1 and 4-(trifluoromethoxy)phenylmagnesium bromide (CAS registry number: 169222-42-8, 0.50 mol / L THF solution) were used to obtain the labeled compound in the same manner as in Example C3.

[0465] <Example B2> 2-{2,2-dimethyl-4-[4-(trifluoromethoxy)phenyl]tetrahydro-2H-pyran-4-yl}ethaneamine The compound obtained in Example B1 was used, and the same procedure as in Example C4 and Example C5 was followed in order to obtain the compound described above.

[0466] <Example B3> Ethyl trans-4-(4-{[(2-{2,2-dimethyl-4-[4-(trifluoromethoxy)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylate The compounds obtained in <Example A4> and <Example B2> were used to obtain the labeled compound in the same manner as in <Example D1>.

[0467] <Example B4> Ethyl trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(trifluoromethoxy)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylate The compound obtained in Example B3 was used to obtain the labeled compound by the same method as in Example D2.

[0468] <Example B5> Trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(trifluoromethoxy)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example B4>, the labeled compound was obtained by the same method as in <Example S4>.

[0469] <Example C1> Ethyl (cis-4-hydroxycyclohexyl) acetate To a solution of cis-2-(4-hydroxycyclohexyl)acetic acid (CAS registry number: 68592-22-3) (2.53 g, 16.0 mmol) in ethanol (46 mL), sulfuric acid (0.086 mL, 1.60 mmol) was added, and the mixture was heated under reflux for 7 hours. The reaction mixture was allowed to return to room temperature, concentrated under reduced pressure, and the residue was diluted with ethyl acetate. The mixture was then washed sequentially with saturated sodium bicarbonate solution and saturated brine. The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the marked compound (2.66 g, 14.3 mmol, yield 89%).

[0470] <Example C2> Ethyl [trans-4-(2-chloro-4-formylphenoxy)cyclohexyl]acetate The compound obtained in Example C1 and 3-chloro-4-hydroxybenzaldehyde (CAS registry number: 2420-16-8) were used to obtain the labeled compound in the same manner as in Example A4.

[0471] <Example C3> Ethyl cyano[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]acetate To a solution of ethyl cyano(2,2-dimethyltetrahydro-4H-pyran-4-ylidene) acetate (8.92 g, 40.0 mmol) in THF (131 mL), copper(I) dimethyl sulfide complex (0.805 g, 3.92 mmol) was added at -78°C and the mixture was stirred at the same temperature for 2 hours. Then, 4-methoxyphenylmagnesium bromide (CAS registry number: 13139-86-1) (0.50 mol / L THF solution, 100 mL, 50 mmol) was added dropwise over 20 minutes at the same temperature. The reaction mixture was stirred for 1.5 hours while gradually increasing the temperature to room temperature, and then left at room temperature overnight. To the reaction mixture, copper(I) dimethyl sulfide complex (0.805 g, 3.92 mmol) was added at -78°C, and the mixture was stirred at the same temperature for 5 minutes. Then, 4-methoxyphenylmagnesium bromide (0.50 mol / L THF solution, 47 mL, 23.5 mmol) was added dropwise over 5 minutes at the same temperature, and the mixture was stirred for 6 hours while increasing the temperature to room temperature. 1 mol / L hydrochloric acid (80 mL) was added to the reaction mixture under ice cooling, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (6.72 g, 20.3 mmol, yield 51%).

[0472] <Example C4> [4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]acetonitrile To a solution of ethyl cyano[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]acetate (10.8 g, 32.6 mmol) in ethylene glycol (109 mL), sodium hydroxide (3.26 g, 81.5 mmol) was added at room temperature, and the mixture was stirred at 150 °C for 7 hours, then left overnight at room temperature. The reaction mixture was cooled with ice, and ice, water, and 1 mol / L hydrochloric acid were added to adjust the pH to 1-2. The mixture was then extracted by DCM. The resulting organic layer was sequentially washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (5.91 g, 22.8 mmol, yield 70%).

[0473] <Example C5> 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine To a solution of [4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]acetonitrile (8.72 g, 33.6 mmol) in THF (224 mL), lithium aluminum hydride (3.19 g, 84.1 mmol) was added over 10 minutes under ice cooling, and the mixture was stirred for 1.5 hours while increasing the temperature to room temperature, then at 35°C for 4 hours, and at 50°C for 2 hours. After cooling, water (3.2 mL) was added to the reaction mixture under ice cooling, followed by the addition of 1 mol / L sodium hydroxide aqueous solution (3.2 mL) and water (9.0 mL). The precipitate was filtered off through Celite and washed with THF. The filtrate was concentrated under reduced pressure, and the resulting residue was purified by amine-modified silica gel column chromatography (hexane / ethyl acetate and ethyl acetate / methanol) to obtain the marked compound (1.74 g, 6.61 mmol, yield 20%).

[0474] <Example C6> Ethyl (trans-4-{2-chloro-4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexyl)acetate The compounds obtained in <Example C2> and <Example C5> were used to obtain the labeled compound in the same manner as in <Example D1>.

[0475] <Example C7> Ethyl [trans-4-(2-chloro-4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexyl]acetate Using the compound obtained in <Example C6>, the labeled compound was obtained by the same method as in <Example D2>.

[0476] <Example C8> [Trans-4-(2-chloro-4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexyl]acetic acid Using the compound obtained in <Example C7>, the labeled compound was obtained by the same method as in <Example S4>.

[0477] <Example D1> Ethyl trans-4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexanecarboxylate 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine (3.89 g, 14.8 mmol) was dissolved in toluene (72.4 mL) at room temperature, to which ethyl trans-4-(4-formylphenoxy)cyclohexanecarboxylate (4.00 g, 14.5 mmol) was added, and the mixture was heated under reflux using a Dean-Stark apparatus. The mixture was stirred for 7 hours while gradually removing the solvent, and then left overnight at room temperature. The reaction mixture was heated under reflux using a Dean-Stark apparatus. The mixture was stirred for 1 hour while gradually removing the solvent, and after cooling, the organic solvent was removed under reduced pressure. The resulting residue was dissolved in methanol (145 mL), and under ice cooling, sodium borohydride (0.714 g, 17.4 mmol) was added, and the mixture was stirred at the same temperature for 5 minutes, and then for 1.5 hours while increasing the temperature to room temperature. Under ice cooling, saturated ammonium chloride aqueous solution and water were added to the reaction mixture, and the mixture was left overnight. The reaction mixture was extracted with DCM, the resulting organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (DCM / methanol) to obtain the labeled compound (5.13 g, 9.79 mmol, yield 68%).

[0478] <Example D2> Ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate To a solution of ethyl trans-4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexanecarboxylate (1.11 g, 2.12 mmol) in DCM (21 mL), triethylamine (0.588 mL, 4.24 mmol) and pivaloyl chloride (421 mg, 3.49 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 2.5 hours. Water was added to the reaction mixture under ice cooling, and the mixture was extracted with DCM. The resulting organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (1.19 g, 1.96 mmol, 92% yield).

[0479] <Example D3> Trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid To a solution of ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate (1.18 g, 1.94 mmol) in methanol (19.4 mL), 1 mol / L aqueous sodium hydroxide solution (9.71 mL, 9.71 mmol) was added at room temperature, and the mixture was stirred at the same temperature for 30 minutes and left overnight. The reaction mixture was neutralized by adding 1 mol / L hydrochloric acid (9.71 mL, 9.71 mmol) under ice cooling, and the organic solvent was removed under reduced pressure. The mixture was extracted by DCM, and the resulting organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (DCM / methanol) to obtain the marked compound (943 mg, 1.63 mmol, yield 84%).

[0480] <Example E1> Ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate The racemic mixture ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate was optically resolved by chiral HPLC [column: CHIRALPAK IC (registered trademark, Daicel Corporation), mobile phase: hexane / ethanol = 50 / 50 (V / V)], and the indicated compound was obtained as the component that eluted first.

[0481] <Example E2> Trans-4-(4-{[(2,2-dimethylpropanoyl){2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example E1>, the labeled compound was obtained by the same method as in <Example S4>.

[0482] <Example F1> Trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-hydroxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid To a solution of trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid (200 mg, 0.345 mmol) in DMF (3.45 mL), sodium thiomethoxide (0.484 g, 6.90 mmol) was added at room temperature and stirred at 100°C for 8 hours, then left overnight at room temperature. Saturated aqueous ammonium chloride solution and water were added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate and DCM. The resulting organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (DCM / methanol) to obtain the marked compound (117 mg, 0.207 mmol, yield 60%).

[0483] <Example F2> Ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-hydroxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate To a solution of trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-hydroxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid (1.33 g, 2.35 mmol) in DMF (23.5 mL), DIPEA (2.05 mL, 11.8 mmol) and iodoethane (0.940 mL, 11.8 mmol) were added at room temperature, the mixture was stirred for 1 hour at room temperature, and left overnight at room temperature. DIPEA (0.819 mL, 4.70 mmol) and iodoethane (0.376 mL, 4.70 mmol) were added to the reaction mixture at room temperature, the mixture was stirred for 10 hours at the same temperature, and left for 2 days at room temperature. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The resulting organic layer was sequentially washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (1.43 g, 2.41 mmol, yield: quantitative).

[0484] <Example F3> Ethyl trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(propan-2-yloxy)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylate To a solution of ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-hydroxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate (80.0 mg, 0.135 mmol) in DMF (1.32 mL), potassium carbonate (146 mg, 1.06 mmol) and 2-bromopropane (0.0991 mL, 1.06 mmol) were added at room temperature, and the mixture was stirred at 130°C for 4.5 hours and left at room temperature for 4 days. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (78.7 mg, 0.124 mmol, yield 92%).

[0485] <Example F4> Trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(propan-2-yloxy)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid The compound obtained in Example F3 was used to obtain the labeled compound in the same manner as in Example S4.

[0486] <Example G1> Trans-4-(4-{[(2,2-dimethylpropanoyl){2-[2,2-dimethyl-4-(4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)tetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate ethyl To a solution of ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-hydroxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate (800 mg, 1.32 mmol) in DCM (6.59 mL), pyridine (1.32 mL, 16.3 mmol) was added under ice cooling, followed by the gradual addition of trifluoromethanesulfonic anhydride (0.333 mL, 1.98 mmol), and the mixture was stirred at the same temperature for 30 minutes and at room temperature for 1 hour. Water was added to the reaction mixture under ice cooling, and the mixture was extracted with a hexane / ethyl acetate mixed solvent (ratio 2 / 1). The resulting organic layer was sequentially washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the labeled compound (915 mg, 1.26 mmol, 96% yield).

[0487] <Example G2> Trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(pyrrolidine-1-yl)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylate ethyl Trans-4-(4-{[(2,2-dimethylpropanoyl){2-[2,2-dimethyl-4-(4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)tetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate ethyl (50.0 mg, 0.0689 mmol) is dissolved in 1,4-dioxane (1.38 mL) at room temperature, and tris(dibenzylideneacetone)dipalladium(0) (6.3 mg, 0.0069 mmol), 2-(di-tert-butylphosphino)biphenyl (4.1 mg, 0.0138 mmol), pyrrolidine (CAS registry number: 123-75-1) (0.0085 mL, 0.103 mmol), and tripotassium phosphate (20.5 mg, 0.0964 mmol) is added. The reaction mixture was mixed with water at room temperature and stirred at 95°C for 9 hours, then left to stand for 3 days. The reaction mixture was then mixed with water at room temperature and extracted with ethyl acetate. The resulting organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (36.2 mg, 0.0560 mmol, yield 81%).

[0488] <Example G3> Trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(pyrrolidine-1-yl)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid The compound obtained in Example G2 was used to obtain the labeled compound in the same manner as in Example S4.

[0489] <Example H1> Trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)-N-(dimethylsulfamoyl)cyclohexanecarboxamide To a 2 mL solution of trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid (85 mg, 0.15 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS registry number: 25952-53-8) (56 mg, 0.29 mmol), and 4-dimethylaminopyridine (54 mg, 0.44 mmol) in DCM, N,N-dimethylsulfamide (CAS registry number: 3984-14-3) (36 mg, 0.29 mmol) was added at room temperature, and the mixture was stirred at room temperature for 1 day. After concentrating the reaction mixture under reduced pressure, the residue was diluted with ethyl acetate and washed sequentially with 1 mol / L hydrochloric acid, water, and saturated saline. The organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (DCM / methanol) to obtain the marked compound (64 mg, 0.093 mmol, yield 62%).

[0490] <Example I1> Ethyl trans-4-(4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(pyridine-2-yl)amino]methyl}phenoxy)cyclohexanecarboxylate To a mixture of ethyl trans-4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexanecarboxylate (60 mg, 0.11 mmol) and 1,4-dioxane (1 mL), 2-bromopyridine (CAS registry number: 109-04-6) (0.030 mL, 0.31 mmol), cesium carbonate (120 mg, 0.368 mmol), and RuPhos Pd G3 (4 mg, 0.005 mmol) were sequentially added, and the mixture was stirred at 100°C for 2 hours. Tripotassium phosphate (100 mg, 0.471 mmol), 2-bromopyridine (0.030 mL, 0.31 mmol), and RuPhos Pd G3 (4 mg, 0.005 mmol) were added to the reaction mixture and the mixture was stirred at 100°C for 8 hours. RuPhos Pd G3 (4 mg, 0.005 mmol) was added to the reaction mixture and the mixture was stirred at 100°C for 3 hours. BrettPhos Pd G3 (4 mg, 0.004 mmol) and cesium carbonate (120 mg, 0.368 mmol) were added to the reaction mixture and the mixture was stirred at 100°C for 4 hours. Water was added to the reaction mixture and extracted with ethyl acetate. All of the resulting organic layers were combined and dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (29.6 mg, 0.0493 mmol, yield 43%).

[0491] <Example I2> Trans-4-(4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(pyridine-2-yl)amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example I1>, the labeled compound was obtained by the same method as in <Example S4>.

[0492] <Example J1> Methyl 3-[4-(4-formylphenoxy)phenyl]-2,2-dimethylpropanoate The marked compound was obtained using methyl 3-(4-hydroxyphenyl)-2,2-dimethylpropanoate (WO2008130514 A1) and 4-fluorobenzaldehyde (CAS registry number: 459-57-4) by the same method as in Example P1.

[0493] <Example J2> Methyl 3-(4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}phenyl)-2,2-dimethylpropanoate 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine (309 mg, 1.17 mmol) and methyl 3-[4-(4-formylphenoxy)phenyl]-2,2-dimethylpropanoate (367 mg, 1.17 mmol) were dissolved in 1,2-dichloroethane (6.0 mL), acetic acid (0.60 mL) was added, and the mixture was stirred at room temperature for 1 hour. Sodium triacetoxyborohydride (324 mg, 1.53 mmol) was added, and the mixture was stirred at room temperature for 20 hours. After adding water and saturated sodium bicarbonate solution to the reaction mixture, it was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain the marked compound (462 mg, 0.825 mmol, yield 70%).

[0494] <Example J3> Methyl 3-[4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)phenyl]-2,2-dimethylpropanoate Methyl 3-(4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}phenyl)-2,2-dimethylpropanoate (241 mg, 0.431 mmol) and pivalic acid (52.8 mg, 0.517 mmol) were dissolved in DMF (6.0 mL), and HATU (205 mg, 0.538 mmol) and DIPEA (0.187 mL, 1.08 mmol) were added. The mixture was stirred at room temperature under a nitrogen atmosphere 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, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (247 mg, 0.384 mmol, yield 89%).

[0495] <Example J4> 3-[4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)phenyl]-2,2-dimethylpropanoic acid The compound obtained in Example J3 was used to obtain the labeled compound by the same method as in Example S4.

[0496] <Example K1> Benzyl (cis-4-hydroxycyclohexyl) acetate 4-hydroxyphenylacetic acid (CAS registry number: 156-38-7) (10.0 g, 65.7 mmol) was dissolved in ethanol (200 mL) and rhodium-alumina (10.0 g) was added. The mixture was stirred at 50°C for 8 hours under a hydrogen atmosphere. Insoluble matter was filtered off through Celite and washed with ethanol. The resulting solution was concentrated to approximately 200 mL, rhodium-alumina (10.0 g) was added, and the mixture was stirred at 50°C for 4 hours under a hydrogen atmosphere. Insoluble matter was filtered off through Celite and washed with ethanol. The filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (130 mL), and then potassium carbonate (18.2 g, 131 mmol) was added at room temperature. Benzyl bromide (11.7 mL, 98.6 mmol) was added dropwise under water cooling, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with diethyl ether, washed sequentially with water, 1 mol / L hydrochloric acid, and saturated saline solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (7.65 g, 30.8 mmol, yield 47%).

[0497] <Example K2> Benzyl [trans-4-(4-formylphenoxy)cyclohexyl]acetate The compound obtained in Example K1 and 4-hydroxybenzaldehyde (CAS registry number: 123-08-0) were used to obtain the labeled compound in the same manner as in Example A4.

[0498] <Example K3> Benzyl (trans-4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexyl)acetate The compounds obtained in <Example K2> and <Example C5> were used to obtain the labeled compound in the same manner as in <Example D1>.

[0499] <Example K4> Benzyl [trans-4-(4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoropropyl)amino]methyl}phenoxy)cyclohexyl]acetate The compound obtained in Example K3 and 3,3,3-trifluoropropionaldehyde (CAS registry number: 460-40-2) were used to obtain the labeled compound in the same manner as in Example T1.

[0500] <Example K5> [Trans-4-(4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoropropyl)amino]methyl}phenoxy)cyclohexyl]acetic acid The compound obtained in Example K4 was used to obtain the labeled compound by the same method as in Example S4.

[0501] <Example L1> Ethyl trans-4-(4-{[(2-{2,2-dimethyl-4-[4-(methylamino)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)(2,2-dimethylpropanoyl)amino]methyl}phenoxy)cyclohexanecarboxylate The compound obtained in Example G1 and methylamine (2.0 mol / L THF solution) were used to obtain the labeled compound in the same manner as in Example G2.

[0502] <Example L2> Trans-4-(4-{[(2-{2,2-dimethyl-4-[4-(methylamino)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)(2,2-dimethylpropanoyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid The compound obtained in Example L1 was used to obtain the labeled compound by the same method as in Example S4.

[0503] <Example M1> 2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine The racemic mixture 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine was optically resolved by chiral HPLC [column: CHIRALCEL OZ-H (registered trademark, Daicel Corporation), mobile phase: hexane / IPA = 60 / 40 (V / V)], and the indicated compound was obtained as the component that subsequently eluted. Analytical conditions: Column: CHIRALCEL OJ-H (registered trademark, Daicel Corporation), Size: 0.46 cm × 25 cm, Flow rate: 1.0 mL / min, Temperature: 30°C, Mobile phase: Hexane / Isopropyl alcohol / Diethylamine = 70 / 30 / 0.2 (V / V / V), Retention time: R-isomer <Example M1> 5.1 min, S-isomer 6.7 min

[0504] <Example M2> 3,3,3-trifluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide 3,3,3-trifluoro-2,2-dimethylpropanoic acid (CAS registry number: 889940-13-0) (18.0 g, 115 mmol) was added to a solution of DMF (150 mL) with HATU (43.8 g, 115 mmol) and stirred at room temperature for 20 minutes. The reaction mixture was cooled to 0°C and stirred for 5 minutes. 2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethaneamine (25.2 g, 95.7 mmol) was added dropwise to a solution of DMF (150 mL) and DIPEA (50 mL, 287 mmol) and stirred at room temperature for 24 hours. The reaction mixture was diluted with ethyl acetate, washed sequentially with sodium bicarbonate solution, water, and saturated saline solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) and dried under reduced pressure to obtain the labeled compound (36.2 g, 90.2 mmol, 94% yield).

[0505] <Example M3> 3,3,3-trifluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}2,2-dimethylpropane-1-amine 3,3,3-trifluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide (24.7 g, 61.5 mmol) was added to a THF (60 mL) solution with borane-THF complex (0.89 mol / L THF solution, 240 mL, 210 mmol) and stirred under reflux for 9 hours. After cooling the reaction mixture to room temperature, methanol (60 mL) was added and stirred under reflux for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. Ethyl acetate was added to the residue, and it was washed sequentially with water and saturated brine. After drying over anhydrous sodium sulfate, it was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (DCM / methanol) and dried under reduced pressure to obtain the marked compound (22.1 g, 57.0 mmol, yield 93%).

[0506] <Example M4> Ethyl trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylate The compounds obtained in <Example M3> and <Example A4> were used to obtain the labeled compound in the same manner as in <Example T1>.

[0507] <Example M5> Trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid The compound obtained in Example M4 was used to obtain the labeled compound by the same method as in Example S4.

[0508] <Example N1> N-[4-(4-bromophenoxy)benzyl]-N-{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide The compound obtained in Example C5 and 4-(4-bromophenoxy)benzaldehyde (Bioorg. Med. Chem. Lett., 2004, 14, 4179-4183.) were used to sequentially perform the same procedures as in Example D1 and Example D2 to obtain the marked compound.

[0509] <Example N2> N-{4-[(4-{[dimethyl(oxide)-λ 6 [Sulfanylidene]amino}cyclohexyl)oxy]benzyl}-N-{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide To a solution of N-[4-(4-bromophenoxy)benzyl]-N-{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide (150 mg, 0.246 mmol) in toluene (5 mL), dimethyl sulfoximine (CAS registry number: 1520-31-6) (35 mg, 0.38 mmol), (S)-(-)-Tol-BINAP (26 mg, 0.038 mmol), cesium carbonate (161 mg, 0.494 mmol), and palladium(II) acetate (6 mg, 0.03 mmol) were added, and the mixture was stirred under a nitrogen atmosphere and reflux for 9 hours. Dimethyl sulfoximine (40 mg, 0.429 mmol), cesium carbonate (170 mg, 0.522 mmol), (S)-(-)-Tol-BINAP (28 mg, 0.041 mmol), and palladium(II) acetate (7 mg, 0.03 mmol) were added to the reaction mixture, and the mixture was stirred under a nitrogen atmosphere and reflux for 8 hours. (S)-(-)-Tol-BINAP (27 mg, 0.040 mmol) and palladium(II) acetate (8 mg, 0.04 mmol) were further added to the reaction mixture, and the mixture was stirred under a nitrogen atmosphere and reflux for 4 hours. After filtering the reaction mixture, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM / methanol) to obtain the marked compound (7 mg, 0.01 mmol, yield 4%).

[0510] <Example O1> Ethyl trans-4-(4-{[(5-fluoropyrimidine-2-yl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate To a mixture of ethyl trans-4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexanecarboxylate (65.5 mg, 0.125 mmol) and 2-butanol (1.5 mL, 16 mmol), 2-chloro-5-fluoropyrimidine (CAS registry number: 62802-42-0) (0.030 mL, 0.24 mmol), 1,8-diazabicyclo[5.4.0]-7-undecene (0.040 mL, 0.27 mmol), and cesium fluoride (1 mg, 0.007 mmol) were sequentially added, and the mixture was stirred at 150°C for 1.5 hours under microwave irradiation. After adding water and saturated saline to the reaction mixture, it was extracted with ethyl acetate. The resulting organic layers were dried together over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (47.4 mg, 0.0765 mmol, yield 61%).

[0511] <Example O2> Trans-4-(4-{[(5-fluoropyrimidine-2-yl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example O1>, the labeled compound was obtained by the same method as in <Example S4>.

[0512] <Example P1> Methyl 2-[4-(4-formylphenoxy)phenyl]propanoate 4-Fluorobenzaldehyde (CAS Registry No.: 459-57-4) (0.637 mL, 5.94 mmol) and methyl 2-(4-hydroxyphenyl)propanoate (J. Med. Chem., 2007, 50, 3984-4002.) (1.07 g, 5.94 mmol) were dissolved in N,N-dimethylacetamide (10 mL), potassium carbonate (2.46 g, 17.8 mmol) was added, and the mixture was stirred at 130°C for 8 hours. After returning to room temperature, it was left to stand overnight. 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, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (878 mg, 3.09 mmol, yield 52%).

[0513] <Example P2> Methyl 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoate The compound indicated was obtained using the compounds obtained in <Example M3> and <Example P1>, by the same method as in <Example T1>.

[0514] <Example P3> 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid Using the compound obtained in <Example P2>, the labeled compound was obtained by the same method as in <Example S4>.

[0515] <Example Q1> Methyl 4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]-2-methylbenzoate The compound obtained in Example C5 and methyl 4-formyl-2-methylbenzoate (CAS registry number: 74733-23-6) were used to obtain the labeled compound in the same manner as in Example J2.

[0516] <Example Q2> Methyl 4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropanoyl)amino]methyl}-2-methylbenzoate 3,3,3-trifluoro-2,2-dimethylpropanoic acid (CAS registry number: 889940-13-0) (1.25 g, 8.04 mmol) was dissolved in DCM (10 mL), DMF (0.05 mL) was added, and the mixture was stirred at room temperature. Oxalyl chloride (0.748 mL, 8.84 mmol) was added, and the mixture was stirred at room temperature for 1 hour. This solution was added to a solution of methyl 4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]-2-methylbenzoate (1.14 g, 2.68 mmol) and triethylamine (2.23 mL, 16.1 mmol) in DCM (15 mL), and the mixture was stirred at room temperature for 24 hours. Water and saturated sodium bicarbonate solution were added to the reaction mixture, and the mixture was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the labeled compound (1.12 g, 1.99 mmol, yield 74%).

[0517] <Example Q3> 4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropanoyl)amino]methyl}2-methylbenzoic acid The compound obtained in Example Q2 was used to obtain the labeled compound in the same manner as in Example S4.

[0518] <Example Q4> 3-[4-(4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropanoyl)amino]methyl}-2-methylbenzoyl)phenyl]propanoic acid 4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropanoyl)amino]methyl}-2-methylbenzoic acid (1.06 g, 1.93 mmol) was dissolved in DCM (10 mL), DMF (0.05 mL) was added, and the mixture was stirred at room temperature. Oxalyl chloride (0.539 mL, 6.36 mmol) was added, and the mixture was stirred at room temperature for 1.5 hours. The solvent was then removed by distillation to obtain the corresponding acid chloride (1.06 g, 1.87 mmol, 97% yield). To the obtained acid chloride (191 mg, 0.336 mmol), [4-(2-ethoxycarbonylethyl)phenyl]boronic acid (CAS registry number: 660440-57-3) (60.0 mg, 0.270 mmol), toluene (8.0 mL), cesium carbonate (225 mg, 0.692 mmol), and tetrakis(triphenylphosphine)palladium (0) (40.6 mg, 0.0351 mmol) were added, and the mixture was stirred at 80°C for 6 hours. After the reaction mixture was allowed to return to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate). The obtained crude product was dissolved in ethanol (4.0 mL), 1 mol / L aqueous sodium hydroxide solution (0.754 mL, 0.754 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, and the residue was neutralized with water and 2 mol / L hydrochloric acid, then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (15.0 mg, 0.0220 mmol, yield 15%).

[0519] <Example R1> Ethyl (2S)-2-ethoxy-3-[4-(4-formylphenoxy)phenyl]propanoate The marked compound was obtained using 4-fluorobenzaldehyde (CAS registry number: 459-57-4) and ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate (CAS registry number: 222555-06-8) by the same method as in Example P1.

[0520] <Example R2> Ethyl (2S)-2-ethoxy-3-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoate The compound indicated was obtained using the compounds obtained in <Example M3> and <Example R1>, by the same method as in <Example T1>.

[0521] <Example R3> (2S)-2-ethoxy-3-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid The compound obtained in Example R2 was used to obtain the labeled compound by the same method as in Example S4.

[0522] <Example S1> Ethyl (cis-4-hydroxycyclohexyl) acetate Under a nitrogen atmosphere, lithium tri(sec-butyl)borohydride (1.07 mol / L THF solution, 39.3 mL, 42.1 mmol) was added dropwise over 30 minutes at -78°C to a solution of 2-(4-oxocyclohexyl)ethyl acetate (CAS registry number: 58012-34-3) (7.75 g, 42.1 mmol) in THF (170 mL) at -78°C. After addition, the mixture was stirred at -78°C for 2 hours. Saturated ammonium chloride aqueous solution and water were added to the reaction mixture, and the mixture was returned to room temperature. Under reduced pressure, the THF was removed by distillation, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the marked compound (6.13 g, 32.9 mmol, yield 78%).

[0523] <Example S2> Ethyl {trans-4-[(5-formylpyridine-2-yl)oxy]cyclohexyl}acetate The compound obtained in Example S1 and 6-hydroxynicotinaldehyde (CAS registry number: 106984-91-2) were used to obtain the marked compound in the same manner as in Example A4.

[0524] <Example S3> Ethyl {trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}pyridine-2-yl)oxy]cyclohexyl}acetate The compounds obtained in <Example S2> and <Example M3> were used to obtain the labeled compound in the same manner as in <Example T1>.

[0525] <Example S4> {Trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}pyridine-2-yl)oxy]cyclohexyl}acetic acid To a solution of ethyl {trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}pyridine-2-yl)oxy]cyclohexyl}acetate (390 mg, 0.588 mmol) in methanol (11.8 mL), 1 mol / L aqueous sodium hydroxide solution (2.94 mL, 2.94 mmol) was added at room temperature, and the mixture was stirred at 50°C for 30 minutes, then left overnight at room temperature. 1 mol / L hydrochloric acid (2.94 mL, 2.94 mmol) was added to the reaction mixture at room temperature, and the mixture was extrac...

Claims

1. The following formula (1): 【Chemistry 1】 [In the formula, A is -O-, -S-, -NR ａ - or -CR ｂ R ｃ - and Here, R ａ is hydrogen or C １－３ It is alkyl, R ｂ and R ｃ These are, independently, hydrogen, halogen, or C １－３ It is alkyl, and The alkyl group is either unsubstituted or substituted with one to three halogens. n Rs １ are each independently halogen, hydroxy, -CN, C １－６ alkyl, C ２－６ alkenyl, -O-C １－６ alkyl, -N(H)-C １－３ alkyl, -N(C １－３ alkyl), ２ C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, and Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R ２ and R ３ These are, independently, hydrogen, halogen, and C. １－６ Alkyl, or C ２－６ It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R ４ C １－６ Alkyl, -C(=O)-R ｄ (R ｄ C １－６ Alkyl, C ２－５ Alkenil, C ３－７ (Representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C ６－１２ It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C １－６ Alkyl is either unsubstituted or has 1 to 3 halogens, C ３－７ Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds each have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q １ C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ A cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L １ These are single bonds, -O-, -S-, -NH-, C １－３ Alkylene, C ２－３ Alkenylene, -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)- Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q ２ C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C ５－１２ The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aforementioned aromatic hydrocarbon rings, aromatic heterocycles, cycloalkane rings, heterocycloalkane rings, cycloalkene rings, heterocycloalkene rings, spirocycloalkane rings, and spiroheterocycloalkane rings are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R ５ C １－６ Alkyl, carboxy, hydroxy, or The following formula: 【Chemistry 2】 It is a base represented by, Here, Said C １－６ Alkyl is either unsubstituted or carboxy, hydroxy, and -O-C １－６ It is substituted with one or two groups selected from the group consisting of alkyls, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof.

2. A is -O- or -CR ｂ R ｃ - The compound according to claim 1 or a pharmaceutically acceptable salt thereof.

3. n R １ However, each is independent of halogen and -O-C. １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C) １－３ Alkyl) ２ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, which is a 3- to 7-membered heterocycloalkyl group, wherein the heterocycloalkyl group has one or two nitrogen atoms as ring member atoms.

4. R ２ and R ３ However, each independently, hydrogen or C １－６ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is alkyl.

5. R ４ However, C １－６ Alkyl, -C(=O)-R ｄ , or a heteroaryl with 6 to 12 members, Here, The aforementioned R ｄ C １－６ It is alkyl, Said C １－６ The alkyl group is either unsubstituted or contains one to three halogens or carbon atoms. ３－７ It is substituted with a cycloalkyl group, and The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the heteroaryl has one or two nitrogen atoms as ring member atoms.

6. Ring Q １ However, C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane ring, or C ３－７ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is a cycloalkene ring, and the aromatic heterocycle has one or two nitrogen atoms as ring member atoms.

7. L １ However, it has a single bond, -O-, C １－３ The compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is alkylene or -C(=O)-.

8. Ring Q ２ However, C ６－１２ A monocyclic or bicyclic aromatic hydrocarbon ring, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ The compound according to claim 1 or a pharmaceutically acceptable salt thereof, comprising a cycloalkene ring or a 5- to 12-membered spiroheterocycloalkane ring, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring each have one or two nitrogen atoms as ring member atoms.

9. The following formula (1'): 【Transformation 3】 [In the formula, A is -O- or -CF ２ - and R １ -O-C １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C) １－３ Alkyl) ２ Alternatively, a 4- to 6-membered heterocycloalkyl group having one nitrogen atom as a ring member atom, R ２ and R ３ each independently represents hydrogen or C １－６ alkyl, R ４ C may be substituted with 1 to 3 halogens. １－６ Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C １－６ C may be substituted with an alkyl group or one trifluoromethyl group. ３－６ A cycloalkylmethyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q １ is a benzene ring which may have one or two groups selected from the group consisting of halogen and C １－３ alkyl, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having one or two nitrogen atoms as ring member atoms, C ４－７ cycloalkane ring, or C ４－７ cycloalkene ring, and L １ This is a single bond, -O-, -CH ２ - or -C (=O)-, Ring Q ２ This is a benzene ring which may be substituted with one halogen, C ４－７ A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. ４－７ A cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, and R ５ These are carboxy, hydroxy, and -O-C １－６ C may have one or two groups selected from the group consisting of alkyl groups. １－６ Alkyl, carboxy, hydroxy, or the following formula: 【Chemistry 4】 A compound represented by [a group represented by ] or a pharmaceutically acceptable salt thereof.

10. A is -O-, R ２ However, it is methyl, R ３ However, it is methyl, R ４ However, C may be substituted with 1 to 3 halogens. １－６ Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C １－６ Alkyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q １ However, halogen and C １－３ A benzene ring or pyridine ring which may have one group selected from the group consisting of alkyl groups, L １ However, it is a single bond, -O-, or -C(=O)-, and Ring Q ２ However, the benzene ring, C ４－７ Cycloalkane ring, or C ４－７ It is a cycloalkene ring. The compound according to claim 9 or a pharmaceutically acceptable salt thereof.

11. R １ However, it is methoxy, and R ４ However, it is 3,3,3-trifluoro-2,2-dimethylpropyl. The compound according to claim 9 or a pharmaceutically acceptable salt thereof.

12. The following groups: trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid, 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid, {trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}pyridine-2-yl)oxy]cyclohexyl}acetic acid, [Trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexyl]acetic acid, (4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[biphenyl]-4-carboxylic acid, [(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methanol, and, tert-butyl4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazine-1-carboxylate Any one compound selected from or a pharmaceutically acceptable salt thereof.

13. Formula (2) below: 【Transformation 5】 [In the formula, A is -O-, -S-, -NR ａ - or -CR ｂ R ｃ - and Here, R ａ is hydrogen, or C １－３ It is alkyl, R ｂ and R ｃ These are, independently, hydrogen, halogen, or C １－３ It is alkyl, and The alkyl group is either unsubstituted or substituted with one to three halogens. n R １ These are, independently, halogen, hydroxyl, -CN, and C. １－６ Alkyl, C ２－６ Alkenyl, -O-C １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C) １－３ Alkyl) ２ , C ３－７ Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R ２ and R ３ These are, independently, hydrogen, halogen, and C. １－６ Alkyl, or C ２－６ It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R ４ C １－６ Alkyl, -C(=O)-R ｄ (R ｄ C １－６ Alkyl, C ２－５ Alkenil, C ３－７ (Representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C ６－１２ It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C １－６ Alkyl is either unsubstituted or has 1 to 3 halogens, C ３－７ Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds each have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q １ C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ A cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L １ These are single bonds, -O-, -S-, -NH-, C １－３ Alkylene, C ２－３ Alkenylene, -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)- Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q ２ C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C ５－１２ The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aforementioned aromatic hydrocarbon rings, aromatic heterocycles, cycloalkane rings, heterocycloalkane rings, cycloalkene rings, heterocycloalkene rings, spirocycloalkane rings, and spiroheterocycloalkane rings are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. B is -L ２ -L ３ -L ４ -R ６ And, L ２ C is a single bond. １－６ Alkylene, -C(=O)-, -C(=O)NH-, -(CH ２ ) ｋ -C(=O)NH- (where k is an integer from 1 to 3), or -NHC(=O)-, L ３ C is a single bond. １－６ Alkylene, C ３－６ The cycloalkylene is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, L ４ This is a single bond, -NH-, -N(-R ７ ) - (R ７ is C １－６ (Indicating alkyl), -CH ２ - or -C (=O)-, R ６ These are the E3 ligase binding site, autophagy-recruiting site, lysosome-recruiting site, kinase-recruiting site, phosphatase-recruiting site, glycosyltransferase-recruiting site, acetyltransferase-recruiting site, or ADC, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof. However, the compounds represented by formula (2) above belong to the following group: (3RS)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3R)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3S)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3S)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, and, (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione It is not any one of the compounds selected from or any pharmaceutically acceptable salt thereof.

14. A is -O- or -CR ｂ R ｃ - The compound according to claim 13 or a pharmaceutically acceptable salt thereof.

15. n R １ However, each is independent of halogen and -O-C. １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C) １－３ Alkyl) ２ The compound according to claim 13 or a pharmaceutically acceptable salt thereof, which is a 3- to 7-membered heterocycloalkyl group, wherein the heterocycloalkyl group has one or two nitrogen atoms as ring member atoms.

16. R ２ and R ３ However, each independently, hydrogen or C １－６ The compound according to claim 13 or a pharmaceutically acceptable salt thereof, wherein the compound is alkyl.

17. R ４ However, C １－６ Alkyl, -C(=O)-R ｄ , or a heteroaryl with 6 to 12 members, Here, The aforementioned R ｄ C １－６ It is alkyl, Said C １－６ The alkyl group is either unsubstituted or contains one to three halogens or carbon atoms. ３－７ It is substituted with a cycloalkyl group, and The compound according to claim 13 or a pharmaceutically acceptable salt thereof, wherein the heteroaryl has one or two nitrogen atoms as ring member atoms.

18. Ring Q １ However, C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane ring, or C ３－７ The compound according to claim 13 or a pharmaceutically acceptable salt thereof, wherein the compound is a cycloalkene ring, and the aromatic heterocycle has one or two nitrogen atoms as ring member atoms.

19. L １ However, it has a single bond, -O-, C １－３ The compound according to claim 13, or a pharmaceutically acceptable salt thereof, which is alkylene or -C(=O)-.

20. Ring Q ２ However, C ６－１２ A monocyclic or bicyclic aromatic hydrocarbon ring, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ The compound according to claim 13 or a pharmaceutically acceptable salt thereof, wherein the compound is a cycloalkene ring or a 5- to 12-membered spiroheterocycloalkane ring, the heterocycloalkane ring and the spiroheterocycloalkane ring having one or two nitrogen atoms as ring member atoms.

21. The following formula (2'): 【Transformation 6】 [In the formula, A is -O- or -CF ２ - and R １ -O-C １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C) １－３ Alkyl) ２ Alternatively, a 4- to 6-membered heterocycloalkyl group having one nitrogen atom as a ring member atom, R ２ and R ３ These are, independently, hydrogen or C １－６ It is alkyl, R ４ C may be substituted with 1 to 3 halogens. １－６ Alkyl, may be substituted with 1 to 3 halogens -C(=O)-C １－６ C may be substituted with an alkyl group or one trifluoromethyl group. ３－６ A cycloalkylmethyl, or a six-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q １ is halogen and C １－３ A benzene ring which may have one or two groups selected from the group consisting of alkyl groups, a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C ４－７ Cycloalkane ring, or C ４－７ It is a cycloalkene ring, L １ This is a single bond, -O-, -CH ２ - or -C (=O)-, Ring Q ２ This is a benzene ring which may be substituted with one halogen, C ４－７ A cycloalkane ring, which may be substituted with one halogen, is a carbon atom. ４－７ It is a cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, B is -L ２ -L ３ -L ４ -R ６ And, L ２ C is a single bond. １－６ Alkylene, -C(=O)-, -C(=O)NH-, -(CH ２ ) ｋ -C(=O)NH- (where k is an integer from 1 to 3), or -NHC(=O)-, L ３ C is a single bond. １－６ Alkylene, C ３－６ The cycloalkylene is piperazinediyl, piperazine-2-ondiyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, L ４ This is a single bond, -NH-, -N(-R ７ ) - (R ７ is C １－６ (Indicating alkyl), -CH ２ -, or -C (=O)-, and R ６ [The compound represented by is an E3 ligase binding moiety, an autophagy-recruiting moiety, a lysosome-recruiting moiety, a kinase-recruiting moiety, a phosphatase-recruiting moiety, a glycosyltransferase-recruiting moiety, an acetyltransferase-recruiting moiety, or an ADC] or a pharmaceutically acceptable salt thereof. However, the compounds represented by formula (2') above belong to the following group: (3RS)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3R)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3S)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazole-1-yl]piperidine-2,6-dione, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3RS)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3S)-3-[7-({1-[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-carbonyl]piperidine-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl]piperidine-2,6-dione, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, and, (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione It is not any one of the compounds selected from or any pharmaceutically acceptable salt thereof.

22. R ６ The compound according to claim 13 or 21 or a pharmaceutically acceptable salt thereof, wherein the E3 ligase binding portion is the E3 ligase binding portion.

23. The compound according to claim 22, or a pharmaceutically acceptable salt thereof, wherein the E3 ligase binding site is a cereblon (CRBN) binding site.

24. R ６ However, the following formula: 【Transformation 7】 [In the above formula, R ８ is hydrogen, or C １－６ It is alkyl, W, X, Y, and Z are each independently a nitrogen atom, or a halogen, C １－６ Alkyl and -O-C １－６ A carbon atom which may have one group selected from the group consisting of alkyl groups, l, m, and n each independently represent integers from 0 to 3, and The wavy line is L ４ The compound according to claim 13 or 21 or a pharmaceutically acceptable salt thereof, wherein the substituent is selected from [showing the bonding position with].

25. R ６ However, the following formula: 【Transformation 8】 [In the above formula, R ８ is hydrogen, or C １－６ It is alkyl, V is a halogen, and The wavy line is L ４ The compound according to claim 24 or a pharmaceutically acceptable salt thereof, wherein the substituent is one of those selected from [showing the bonding position with].

26. R １ However, it may be substituted with 1 to 3 halogens -O-C １－６ It is alkyl, R ４ However, C may be substituted with 1 to 3 halogens. １－６ C may be substituted with an alkyl group or one trifluoromethyl group. ３－６ It is a cycloalkylmethyl, Ring Q １ However, a benzene ring which may have one or two groups selected from the group consisting of halogens and C1-3 alkyls, a 9 to 10-membered bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms, C ４－７ Cycloalkane ring, or C ４－７ It is a cycloalkene ring, and L １ However, it is a single bond, or -O- The compound according to claim 13 or 21, or a pharmaceutically acceptable salt thereof.

27. A is -O-, R ２ However, it is methyl, and R ３ However, it is methyl. The compound according to claim 13 or 21, or a pharmaceutically acceptable salt thereof.

28. R １ However, it is methoxy, and R ４ However, it is 3,3,3-trifluoro-2,2-dimethylpropyl. The compound according to claim 13 or 21, or a pharmaceutically acceptable salt thereof.

29. Ring Q １ However, it is a benzene ring that may have one halogen, L １ However, it is a single bond, and Ring Q ２ However, it is a cyclohexene ring. The compound according to claim 13 or 21, or a pharmaceutically acceptable salt thereof.

30. A composition for inhibiting Steroidogenic Factor 1, comprising a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, or a compound according to claim 13 or 21 or a pharmaceutically acceptable salt thereof.

31. A composition for inducing the degradation of Steroidogenic Factor 1, comprising the compound described in claim 13 or 21 or a pharmaceutically acceptable salt thereof.

32. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, or a compound according to claim 13 or 21 or a pharmaceutically acceptable salt thereof.

33. The pharmaceutical composition according to claim 32 for the treatment of castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

34. Use of a compound according to any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, or a compound according to claim 13 or 21 or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

35. Formula (10) below: 【Chemistry 9】 [In the formula, A is -O-, -S-, -NR ａ - or -CR ｂ R ｃ - and Here, R ａ is hydrogen or C １－３ It is alkyl, R ｂ and R ｃ These are, independently, hydrogen, halogen, or C １－３ It is alkyl, and The alkyl group is either unsubstituted or substituted with one to three halogens. n R １ These are, independently, halogen, hydroxyl, -CN, and C. １－６ Alkyl, C ２－６ Alkenyl, -O-C １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C) １－３ Alkyl) ２ , C ３－７ Cycloalkyl, or 3- to 7-membered heterocycloalkyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. The cycloalkyl and heterocycloalkyl elements are, independently, unsubstituted or halogenated, unsubstituted C. １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R ２ and R ３ These are, independently, hydrogen, halogen, and C. １－６ Alkyl or C ２－６ It is alkenyl, Here, The alkyl and alkenyl atoms are each independently unsubstituted or substituted with one to three halogens. R ４ C １－６ Alkyl, -C(=O)-R ｄ (R ｄ C １－６ Alkyl, C ２－５ Alkenil, C ３－７ (Representing cycloalkyl or 3- to 7-membered heterocycloalkyl), C ６－１２ It is an aryl, or a heteroaryl with 6 to 12 members. Here, Said C １－６ Alkyl is either unsubstituted or has 1 to 3 halogens, C ３－７ Substituted with cycloalkyl or 3- to 7-membered heterocycloalkyl groups, The aryl, heteroaryl, cycloalkyl, and heterocycloalkyl elements are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The heteroaryl and heterocycloalkyl compounds each have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. Ring Q １ C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ A cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, Here, The aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. L １ These are single bonds, -O-, -S-, -NH-, C １－３ Alkylene, C ２－３ Alkenylene, -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)- Here, The alkylene and alkenylene are each independently unsubstituted or substituted with one to three halogens. Ring Q ２ C ６－１２ Monocyclic or bicyclic aromatic hydrocarbon rings, 6- to 12-membered monocyclic or bicyclic aromatic heterocycles, C ３－７ Cycloalkane rings, 3- to 7-membered heterocycloalkane rings, C ３－７ Cycloalkene rings, 3- to 7-membered heterocycloalkene rings, C ５－１２ The spirocycloalkane ring, or a spiroheterocycloalkane ring with 5 to 12 members, Here, The aforementioned aromatic hydrocarbon rings, aromatic heterocycles, cycloalkane rings, heterocycloalkane rings, cycloalkene rings, heterocycloalkene rings, spirocycloalkane rings, and spiroheterocycloalkane rings are each independently unsubstituted or halogenated, unsubstituted C １－３ Alkyl and C １－３ It is substituted with 1 to 3 groups selected from the group consisting of haloalkyls, and The aforementioned aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms. R １０ C １－６ It is alkyl, Here, Said C １－６ The alkyl group is substituted with one or two 3- to 7-membered heterocycloalkyl groups. The heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, and The heterocycloalkyl group is either unsubstituted or substituted with an amino group protecting group, and A compound represented by [n is an integer from 0 to 3] or a pharmaceutically acceptable salt thereof.

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