3-phenylpropylamine derivative

Abstract

The purpose of the present invention is 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. The present invention relates to a 3-phenylpropylamine derivative compound represented by formula (1), etc., and a polyfunctional molecule comprising a moiety corresponding to the compound represented by formula (1), etc.

Description

3-phenylpropylamine derivatives

[0001] The present invention relates to novel compounds having SF-1 antagonist activity, polyfunctional molecules containing a moiety corresponding to said compounds, particularly SF-1 degradation inducers, and pharmaceutical compositions containing them.

[0002] Steroidogenic factor 1 (SF1) is a nuclear receptor expressed in the adrenal cortex, gonads, hypothalamus, and pituitary gland. It is an important molecule for the development of the adrenal glands and gonads (Non-Patent Document 1). Adrenal tumors have been reported in mice overexpressing SF-1 (Non-Patent Document 2), and SF-1 protein has been overexpressed in adrenocortical cancer tissue (Non-Patent Document 3). Therefore, SF-1 is thought to contribute to the development and progression of adrenal tumors. SF-1 has also been shown to regulate the expression of steroid hormone synthesis enzymes, such as CYP11A1 and CYP17A1, in the adrenal cortex and testis, thereby inducing the production of steroid hormones, such as androgens (Non-Patent Documents 4 and 5). Androgens are important for the development and growth of prostate cancer. Although hormonal therapy, such as castration, can suppress its progression in the early stages of treatment, prostate cancer can progress to castration-resistant prostate cancer, which is resistant to hormonal therapy. It is known that the growth of castration-resistant prostate cancer depends on androgens derived from the adrenal gland (Non-Patent Document 6).

[0003] Recently, the usefulness of heterobifunctional molecules, which combine a target protein-binding moiety with an endogenous effector molecule-recruiting moiety via a linker, has been reported. Heterobifunctional molecules bring the target protein and the endogenous effector molecule into physical proximity, thereby causing changes in the target protein and exerting the desired effect (Non-Patent Document 7).

[0004] Targeted protein degradation (TPD) is one such technique that utilizes heterobifunctional molecules. TPD induces degradation of target proteins. It uses heterobifunctional molecules, consisting of a binder moiety that binds to the target protein and a binder moiety that binds to E3 ligase via a linker, to induce intracellular complex formation between the target protein and E3 ligase, thereby inducing ubiquitination and degradation of the target protein, demonstrating potent physiological activity. Although over 600 E3 ligases have been identified, only a limited number of them have been used in TPD, particularly cereblon (CRBN) and von Hippel-Lindau (VHL) (Non-Patent Document 8). In particular, binder moieties that bind to CRBN (also known as "CRBN ligands") have been widely used in TPD, and their diverse structures and usefulness have been reported (Patent Documents 1-9, Non-Patent Document 9). While a variety of proteins have been reported as targets of TPD, no targeted protein degradation inducers targeting SF-1 have been reported to date.

[0005] International Publication No. 2017 / 197051 International Publication No. 2018 / 237026 International Publication No. 2019 / 060693 International Publication No. 2019 / 060742 International Publication No. 2019 / 099868 International Publication No. 2019 / 199816 International Publication No. 2020 / 210630 International Publication No. 2022 / 081927 International Publication No. 2022 / 081928

[0006] Parker KL, Schimmer BP, Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev., 1997; 18: 361-77.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.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.Relav L, Doghman-Bouguerra M, Ruggiero C, Muzzi JCD, Figueiredo BC, Lalli E, Steroidogenic Factor 1, a Goldilocks Transcription Factor from Adrenocortical Organogenesis to Malignancy. Int J Mol Sci., 2023; 24: 3585.Lin L, Achermann J, C: Steroidogenic Factor-1 (SF-1, Ad4BP, NR5A1) and Disorders of Testis Development. Sex Dev., 2008; 2: 200-209.Attard G, Sarker D, Reid A, Molife R, Parker C, de Bono JS, Improving the outcome of patients with castration-resistant prostate cancer through rational drug development.Br J Cancer., 2006 9; 95: 767-74.Liwen Hua, et al., Beyond Proteolysis-Targeting Chimeric Molecules: Designing Heterobifunctional Molecules Based on Functional Effectors. J. Med. Chem., 2022; 65: 8091-8112.Chaoguo Cao, et al. Chemistries of bifunctional PROTAC degraders. Chem. Soc. Rev., 2022: 51: 7066-7114.Alexander Kazantsev and Mikhail Krasavin, Ligands for cereblon: 2017-2021 patent overview. Expert Opinion on Therapeutic Patents. 2022; 32: 2: 171-190.

[0007] An object of the present invention is to provide novel compounds having SF-1 antagonist activity, polyfunctional molecules containing a moiety corresponding to the compounds, particularly SF-1 degradation inducers (SF-1 degraders). A further object of the present invention is to provide compositions for inhibiting SF-1, compositions for inducing SF-1 degradation, or pharmaceutical compositions containing the compounds or polyfunctional molecules. Another object of the present invention is to provide methods for treating diseases (particularly cancers such as castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, and breast cancer, Cushing's syndrome, or primary aldosteronism) comprising administering the compounds or polyfunctional molecules. Yet another object of the present invention is to provide intermediates that can be used in the production of the compounds or polyfunctional molecules.

[0008] As a result of extensive research, the present inventors have found that 3-phenylpropylamine derivative compounds represented by the following formula (1) or the like have SF-1 antagonist activity, and have also found that polyfunctional molecules containing a moiety corresponding to the compound represented by the formula (1) or the like can degrade SF-1 protein and inhibit the proliferation of tumor cells, thereby completing the present invention. That is, the present invention relates to the following. [1] A compound represented by the following formula (1):

[0009]

[0010] [Wherein, A is —O—, —S—, —NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxy, —CN, or 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, wherein said alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and said cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogens, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, wherein １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, —O—, —S—, —NH—, C １－３ Alkylene, C ２－３ alkenylene, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, or —OC(═O)—, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; and ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ５ is C １－６ alkyl, carboxy, hydroxy, or the following formula:

[0011]

[0012] wherein C is a group represented by １－６Alkyl is unsubstituted or includes carboxy, hydroxy and -O-C １－６ and n is an integer of 0 to 3, or a pharmaceutically acceptable salt thereof. [2] A is a compound represented by the formula (I) or (II), ｂ R ｃ [3] The compound according to [1], wherein n R １ each independently represents a halogen, —O—C １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 3- to 7-membered heterocycloalkyl, wherein the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms, or a pharmaceutically acceptable salt thereof according to [1] or [2]. [4] R ２ and R ３ are each independently hydrogen or C １－６ [5] The compound according to any one of [1] to [3], or a pharmaceutically acceptable salt thereof, wherein R is alkyl. ４ But C １－６ Alkyl, —C(═O)—R ｄ or a 6- to 12-membered heteroaryl, wherein R ｄ is C １－６ alkyl, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens or C ３－７ [6] The compound according to any one of [1] to [4], or a pharmaceutically acceptable salt thereof, wherein the ring Q is substituted with a cycloalkyl, and the heteroaryl has one or two nitrogen atoms as ring member atoms. １ But C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, or C ３－７[7] The compound according to any one of [1] to [5], wherein the aromatic heterocycle is a cycloalkene ring and has one or two nitrogen atoms as ring member atoms, or a pharmaceutically acceptable salt thereof. １ is a single bond, —O—, C １－３ [8] The compound according to any one of [1] to [6], wherein ring Q is alkylene, or —C(═O)—, or a pharmaceutically acceptable salt thereof. ２ But C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of C ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ [9] The compound according to any one of [1] to [7], wherein the heterocycloalkane ring or the spiroheterocycloalkane ring has one or two nitrogen atoms as ring member atoms, or a pharmaceutically acceptable salt thereof, represented by the following formula (1'):

[0013]

[0014] [Wherein, A is —O— or —CF ２ - and R １ is a halogen, —O—C optionally substituted with 1 to 3 halogens １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member, R ２ and R ３ are each independently hydrogen or C １－６ alkyl, R ４ is C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), and ring Q１ is halogen and C １－３ a benzene ring optionally having one or two groups selected from the group consisting of alkyl; 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 is a cycloalkene ring, １ represents a single bond, —O—, —CH ２ - or -C(=O)-, and ring Q ２ represents a benzene ring optionally substituted with one halogen atom, C ４－７ a cycloalkane ring, a C optionally substituted with one halogen atom; ４－７ a cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, and R ５ is carboxy, hydroxy and —O—C １－６ C optionally having 1 or 2 groups selected from the group consisting of alkyl １－６ alkyl, carboxy, hydroxy, or a group represented by the formula:

[0015]

[0016]

[10] A is -O-, and R ２ is methyl, R ３ is methyl, R ４ C optionally substituted with 1 to 3 halogen atoms １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), ring Q １ is halogen and C １－３ a benzene ring or a pyridine ring, each of which may have one group selected from the group consisting of alkyl; １ is a single bond, —O—, or —C(═O)—, and ring Q ２ is a benzene ring, C ４－７ Cycloalkane ring, or C４－７

[11] The compound according to [9], or a pharmaceutically acceptable salt thereof, wherein R is a cycloalkene ring. １ is methoxy, and R ４is 3,3,3-trifluoro-2,2-dimethylpropyl, or a pharmaceutically acceptable salt thereof.

[12] 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}pyridin-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 or a pharmaceutically acceptable salt thereof.

[13] A polyfunctional molecule comprising a moiety corresponding to the compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof.

[14] A polyfunctional molecule further comprising another functional moiety, wherein the moiety corresponding to the compound or a pharmaceutically acceptable salt thereof is R. 5

[15] The multifunctional molecule according to

[14] , wherein the other functional moiety 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.

[16] The multifunctional molecule according to

[14] , wherein the other functional moiety is an E3 ligase-binding moiety.

[17] The multifunctional molecule according to

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

[18] A multifunctional molecule according to the following formula (2):

[0017]

[0018] [Wherein, A is —O—, —S—, —NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxy, —CN, or 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 ３－７cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein said alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and said cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogens, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, wherein １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, —O—, —S—, —NH—, C １－３ Alkylene, C ２－３ alkenylene, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, or —OC(═O)—, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; and ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; B is -L ２ -L ３ -L ４ -R ６ and L ２ is a single bond, C １－６ Alkylene, —C(═O)—, —C(═O)NH—, —(CH ２ ) ｋ -C(=O)NH- (k is an integer of 1 to 3), or -NHC(=O)-, L ３ is a single bond, C １－６ Alkylene, C ３－６ cycloalkylene, piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl; L ４ represents a single bond, -NH-, -N(-R ７ )-(R ７ is C １－６ alkyl), -CH ２ - or -C(=O)-, and R ６ 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, and n is an integer of 0 to 3, or a pharmaceutically acceptable salt thereof.

[19] A compound represented by the formula (I) or (II) above is -O-, or -CR ｂ R ｃ

[20] The compound according to

[18] , wherein n R １ each independently represents a halogen, —O—C １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２or a 3- to 7-membered heterocycloalkyl, wherein the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms, or a pharmaceutically acceptable salt thereof according to

[18] or

[19] .

[21] R ２ and R ３ are each independently hydrogen or C １－６

[22] The compound according to any one of

[18] to

[20] , or a pharmaceutically acceptable salt thereof, wherein R is alkyl. ４ But C １－６ Alkyl, —C(═O)—R ｄ or a 6- to 12-membered heteroaryl, wherein R ｄ is C １－６ alkyl, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens or C ３－７ The compound according to any one of

[18] to

[21] , or a pharmaceutically acceptable salt thereof, wherein the ring Q is substituted with a cycloalkyl, and the heteroaryl has one or two nitrogen atoms as ring member atoms.

[23] Ring Q １ But C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, or C ３－７

[24] The compound according to any one of

[18] to

[22] , wherein the aromatic heterocycle is a cycloalkene ring and has one or two nitrogen atoms as ring member atoms, or a pharmaceutically acceptable salt thereof. １ is a single bond, —O—, C １－３

[25] The compound according to any one of

[18] to

[23] , wherein ring Q is alkylene, or —C(═O)—, or a pharmaceutically acceptable salt thereof. ２ But C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of C ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７

[26] The compound according to any one of

[18] to

[24] , wherein the heterocycloalkane ring or the spiroheterocycloalkane ring has one or two nitrogen atoms as ring member atoms, or a pharmaceutically acceptable salt thereof, represented by the following formula (2'):

[0019]

[0020] [Wherein, A is —O— or —CF ２ - and R １ is a halogen, —O—C optionally substituted with 1 to 3 halogens １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member, R ２ and R ３ are each independently hydrogen or C １－６ alkyl, R ４ is C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), and ring Q １ is halogen and C １－３ a benzene ring optionally having one or two groups selected from the group consisting of alkyl; 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 is a cycloalkene ring, １ represents a single bond, —O—, —CH ２ - or -C(=O)-, and ring Q ２ represents a benzene ring optionally substituted with one halogen atom, C ４－７a cycloalkane ring, a C optionally substituted with one halogen 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 is a single bond, C １－６ Alkylene, —C(═O)—, —C(═O)NH—, —(CH ２ ) ｋ -C(=O)NH- (k is an integer of 1 to 3), or -NHC(=O)-, L ３ is a single bond, C １－６ Alkylene, C ３－６ cycloalkylene, piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl; L ４ represents a single bond, -NH-, -N(-R ７ )-(R ７ is C １－６ alkyl), -CH ２ - or -C(=O)-, and R ６ 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.

[27] R ６

[28] The compound according to any one of

[18] to

[26] , or a pharmaceutically acceptable salt thereof, wherein R is an E3 ligase binding moiety.

[29] The compound according to

[27] , or a pharmaceutically acceptable salt thereof, wherein R is an E3 ligase binding moiety.

[30] The compound according to

[28] , or a pharmaceutically acceptable salt thereof, wherein R is an E3 ligase binding moiety.

[31] The compound according to

[27] , or a pharmaceutically acceptable salt thereof, wherein R is an E3 ligase binding moiety.

[32] The compound according to

[27] , or a pharmaceutically acceptable salt thereof, wherein R is an E3 ligase binding moiety.

[33] The compound according to

[27] , or a pharmaceutically acceptable salt thereof, wherein R is an E3 ligase binding moiety. ６ is expressed by the following formula:

[0021]

[0022] [wherein R ８ is hydrogen or C １－６alkyl; W, X, Y, and Z are each independently a nitrogen atom, a halogen atom, or C １－６ Alkyl and —O—C １－６ a carbon atom optionally having one group selected from the group consisting of alkyl; l, m, and n each independently represent an integer of 0 to 3; and the wavy line represents L. ４

[30] The compound according to any one of

[18] to

[28] , or a pharmaceutically acceptable salt thereof, wherein R is any group selected from the group consisting of ６ is expressed by the following formula:

[0023]

[0024] [In the formula, R ８ is hydrogen or C １－６ is alkyl, V is halogen, and the wavy line represents L ４

[31] The compound according to

[29] , or a pharmaceutically acceptable salt thereof, wherein R is any group selected from the group consisting of １ is —O—C optionally substituted with 1 to 3 halogens １－６ alkyl, R ４ C optionally substituted with 1 to 3 halogen atoms １－６ C optionally substituted with alkyl or one trifluoromethyl ３－６ cycloalkylmethyl, and ring Q １ is halogen and C １－６ a benzene ring optionally having one or two groups selected from the group consisting of alkyl; 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 is a cycloalkene ring, and L １

[32] The compound according to any one of

[18] to

[30] , wherein R is a single bond or —O—, or a pharmaceutically acceptable salt thereof. ２ is methyl, and R ３

[33] The compound according to any one of

[18] to

[31] , or a pharmaceutically acceptable salt thereof, wherein R is methyl.１ is methoxy, and R ４

[34] The compound according to any one of

[18] to

[32] , wherein ring Q is 3,3,3-trifluoro-2,2-dimethylpropyl, or a pharmaceutically acceptable salt thereof. １ is a benzene ring optionally having one halogen atom, and L １ is a single bond, and ring Q ２is a cyclohexene ring.

[35] The compound according to any one of

[18] to

[33] , or a pharmaceutically acceptable salt thereof, of 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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperazin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione, and [35-2] Any one compound selected from the following group: (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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione or a pharmaceutically acceptable salt thereof.(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-benzimidazol-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-benzimidazol-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-benzimidazol-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]quinolin-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]quinolin-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]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione, C (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]quinoxalin-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 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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl}piperidine-2,6-dione monobenzenesulfonate. [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]quinolin-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]quinolin-1(2H)-yl]piperidine-2,6-dione monobenzenesulfonate. [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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl}piperidine-2,6-dione A crystalline benzenesulfonate salt, which has 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 radiation (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]quinolin-1(2H)-yl]piperidine-2,6-dione A crystalline benzenesulfonate salt, which has 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 radiation (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}piperazin-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}piperazin-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]quinolin-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]quinolin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl}piperidine-2,6-dione A crystalline ethanesulfonate salt, which has 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 radiation (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]quinolin-1(2H)-yl]piperidine-2,6-dione A crystalline ethanesulfonate salt, which has 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 radiation (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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione 10-camphorsulfonate. [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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione 10-camphorsulfonate. [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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione 10-camphorsulfonate. [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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione 10-camphorsulfonate. [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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl}piperidine-2,6-dione A crystalline form of 10-camphorsulfonate, which has 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 radiation (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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione A crystalline form of 10-camphorsulfonate, which has 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 radiation (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}piperazin-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}piperazin-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]quinoxalin-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]quinoxalin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A crystalline ethanesulfonate salt, which has 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 radiation (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 ethanesulfonate A crystalline ethanesulfonate salt, which has 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 radiation (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}piperazin-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}piperazin-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]quinoxalin-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]quinoxalin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A crystalline salicylate salt, which has 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 radiation (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 crystalline salicylate salt 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 radiation (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}piperazin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione monobenzenesulfonate. [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]quinoxalin-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]quinoxalin-1(2H)-yl]piperidine-2,6-dione monobenzenesulfonate. [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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A crystalline benzenesulfonate salt, which has 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 radiation (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 crystalline benzenesulfonate salt, which has 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 radiation (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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione 10-camphorsulfonate. [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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione-10-camphorsulfonate. [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]quinoxalin-1(2H)-yl]piperidine-2,6-dione 10-camphorsulfonate salt. [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-camphorsulfonate. [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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione A crystalline form of 10-camphorsulfonate, which has 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 a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (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 [42-1] A compound or a pharmaceutically acceptable salt thereof according to any one of [1] to

[12] , a polyfunctional molecule according to any one of

[13] to

[17] , a compound or a pharmaceutically acceptable salt thereof according to any one of

[18] to [42-6], or a crystal thereof, for inhibiting steroidogenic factor 1.

[43] A composition for inhibiting steroidogenic factor 1, comprising the compound or a pharmaceutically acceptable salt thereof according to any one of [1] to

[12] , the polyfunctional molecule according to any one of

[13] to

[17] , or the compound or a pharmaceutically acceptable salt thereof according to any one of

[18] to [42-1], or a crystal thereof.

[44] A composition for inducing degradation of Steroidogenic Factor 1, comprising the polyfunctional molecule according to any one of

[13] to

[17] , or the compound according to any one of

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

[45] A pharmaceutical composition comprising the compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, the polyfunctional molecule according to any one of

[13] to

[17] , or the compound according to any one of

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

[46] The pharmaceutical composition according to

[45] , for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism. [46-2]

[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, comprising administering an effective amount of the compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, the polyfunctional molecule according to any one of

[13] to

[17] , or the compound according to any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or a crystal thereof, to a subject in need of treatment of 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, comprising administering an effective amount of the compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, the polyfunctional molecule according to any one of

[13] to

[17] , or the compound according to any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or a crystal thereof, to a subject in need of such treatment.

[48] ​​A compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, a polyfunctional molecule according to any one of

[13] to

[17] , or a compound according to any one of

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

[49] Use of the compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, the polyfunctional molecule according to any one of

[13] to

[17] , or the compound according to any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or a crystal thereof, in the manufacture of a medicament 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 the compound according to any one of [1] to

[12] or a pharmaceutically acceptable salt thereof, the polyfunctional molecule according to any one of

[13] to

[17] , or the compound according to any one of

[18] to [42-6] or a pharmaceutically acceptable salt thereof, or a crystal thereof, in the manufacture of a medicament for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, Cushing's syndrome, or primary aldosteronism.

[50] A compound represented by the following formula (10):

[0025]

[0026] [Wherein, A is —O—, —S—, —NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxy, —CN, or C １－６Alkyl, 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, wherein said alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and said cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogens, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, wherein １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, —O—, —S—, —NH—, C １－３ Alkylene, C ２－３ alkenylene, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, or —OC(═O)—, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; and ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R １０ is C １－６ alkyl, wherein said C １－６ a compound or a pharmaceutically acceptable salt thereof, wherein the alkyl is substituted with one or two 3- to 7-membered heterocycloalkyls, the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, the heterocycloalkyl is unsubstituted or substituted with an amino-protecting group, and n is an integer from 0 to 3. For example, when a range is indicated by a number such as "

[18] to [42-6]" above, and the range includes a branch number such as [36-3] or [42-4], the branch number is also included in the range.

[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. Furthermore, since the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity, it can be combined with other functional moieties and used as a partial structure in a larger molecule (e.g., a multifunctional molecule). 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. Furthermore, by combining a moiety corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof with another functional moiety, it can also be used as an SF-1 binding moiety in a larger molecule (e.g., a multifunctional molecule). Among these, a multifunctional molecule containing a moiety corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof and an E3 ligase binding moiety, particularly a compound represented by formula (2) of the present invention or a pharmaceutically acceptable salt thereof, or a crystal thereof, can degrade SF-1 protein and inhibit tumor cell proliferation. Therefore, it can be used as an SF-1 inhibitor and SF-1 degrader, as well as for the treatment of SF-1-related diseases such as adrenocortical carcinoma and castration-resistant prostate cancer.

[0028] Powder X-ray diffraction pattern of the crystal obtained in Example CI1. The vertical axis of the figure shows diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. Powder X-ray diffraction pattern of the crystal obtained in Example CJ1. The vertical axis of the figure shows diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. Powder X-ray diffraction pattern of the crystal obtained in Example CK1. The vertical axis of the figure shows diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. Powder X-ray diffraction pattern of the crystal obtained in Example CL1. The vertical axis of the figure shows diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. Powder X-ray diffraction pattern of the crystal obtained in Example CM1. The vertical axis of the figure shows diffraction intensity in counts / second (cps), and the horizontal axis shows the value of the diffraction angle 2θ. 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 diffraction angle 2θ. 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 diffraction angle 2θ.

[0029] 1. Definitions Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the art. In the event of a discrepancy between the meaning defined herein and the meaning commonly understood by those of ordinary skill in the art, the meaning defined herein shall prevail. Preferred methods and materials are described below; however, methods and materials similar or equivalent to those described herein can be used in practicing or testing the present invention. All references (including patent and non-patent literature) described herein are incorporated by reference in their entirety. The materials, methods, and examples disclosed herein are illustrative only and are not intended to be limiting.

[0030] As used herein, steroidogenic factor 1 refers to a protein encoded by the NR5A1 gene, and may be abbreviated or synonymously referred to as SF-1, hSF-1, SF1, Ad4BP, AD4BP, ELP, FTZ1, TZF1, POF7, SPGF8, SRXX4, or SRXY3.

[0031] As used herein, "antagonist" refers to a substance that reduces, interferes with, or neutralizes the action, activity, or effect of another substance. Accordingly, as used herein, "SF-1 antagonist" refers to a substance that reduces, interferes with, or neutralizes the action, activity, or effect of SF-1.

[0032] As used herein, "halogen" refers to a fluorine atom (F), a chlorine atom (Cl), a bromine atom (Br), and an iodine atom (I).

[0033] As used herein, "alkyl" means straight or branched chain alkyl. １－６ "Alkyl" means an alkyl having 1 to 6 carbon atoms, １－３ "Alkyl" means an alkyl having 1 to 3 carbon atoms. Examples of "alkyl" include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, n-pentyl, n-hexyl, and the like.

[0034] As used herein, "alkylene" means straight or branched chain alkylene. １－６ "Alkylene" means an alkylene having 1 to 6 carbon atoms, １－３ "Alkylene" means an alkylene having 1 to 3 carbon atoms. Examples of "alkylene" include, but are not limited to, methylene, ethylene, n-propylene, i-propylene, n-butylene, i-butylene, s-butylene, t-butylene, n-pentylene, n-hexylene, and the like.

[0035] As used herein, "alkenyl" refers to straight or branched chain alkenyl. ２－６ "Alkenyl" means an alkenyl having 2 to 6 carbon atoms, ２－５"Alkenyl" means an alkenyl having 2 to 5 carbon atoms. Examples of "alkenyl" include, but are not limited to, ethenyl (vinyl), 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, buta-2,3-dienyl, pentenyl, hexenyl, and the like.

[0036] As used herein, "alkenylene" refers to straight or branched chain alkenylene. ２－３ "Alkenylene" means an alkenylene having 2 to 3 carbon atoms. Examples of "alkenylene" include, but are not limited to, ethenylene (vinylene), 1-propenylene, 2-propenylene, 1-butenylene, 2-butenylene, 3-butenylene, buta-2,3-dienylene, pentenylene, hexenylene, and the like.

[0037] As used herein, "haloalkyl" means alkyl substituted with one or more halogens, and "C １－３ "Haloalkyl" refers to a C alkyl group substituted with one or more halogens. １－３ Examples of "haloalkyl" include, but are not limited to, trifluoromethyl, difluoromethyl, monofluoromethyl, pentafluoroethyl, tetrafluoroethyl, monofluoroethyl, trifluoroethyl, trichloromethyl, and the like.

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

[0039] As used herein, the term "aromatic heterocycle" refers to a monocyclic or polycyclic ring containing one or more heteroatoms other than carbon, such as nitrogen, oxygen, and sulfur, as ring atoms, and at least one of the rings being an aromatic ring. As used herein, the term "heteroaryl" refers to a group derived from an aromatic heterocycle. The term "6- to 12-membered heteroaryl" refers to a heteroaryl consisting of 6 to 12 ring atoms, and the term "6- to 12-membered monocyclic or bicyclic aromatic heterocycle" refers to a monocyclic or bicyclic aromatic heterocycle consisting of 6 to 12 ring atoms. Examples of "aromatic heterocycles" include, but are not limited to, thiophene, pyrrole, pyrazole, triazole, oxazole, oxadiazole, thiazole, pyridine, pyrimidine, pyridazine, pyrazine, quinoline, quinoxaline, benzothiophene, benzimidazole, benzotriazole, benzofuran, and the like. Examples of "heteroaryl" include, but are not limited to, thienyl, pyrrolyl, pyrazolyl, triazolyl, oxazolyl, oxadiazolyl, thiazolyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, quinolyl, quinoxalyl, benzothiophenyl, benzimidazolyl, benzotriazolyl, and benzofuranyl.

[0040] In the present specification, examples of the "6-membered heteroaryl having 1 or 2 nitrogen atoms as ring atoms" include pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, and the like.

[0041] In this specification, examples of the "6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms" include, but are not limited to, 6-membered rings such as pyridine, pyrazine, pyrimidine, and pyridazine; 7-membered rings such as azepine, 1,2-diazepine, 1,3-diazepine, and 1,4-diazepine; 8-membered rings such as azocine; 9-membered rings such as azonine; 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. In this specification, examples of the "9- to 10-membered bicyclic aromatic heterocycle having 1 or 2 nitrogen atoms as ring 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] As used herein, "cycloalkane ring" refers to a hydrocarbon ring that does not contain an unsaturated bond. As used herein, "cycloalkyl" refers to 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 connected by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. As used herein, "C ３－７ Cycloalkane ring" and "C ４－７ "Cycloalkane ring" means a cycloalkane ring having 3 to 7 and 4 to 7 carbon atoms, respectively, and "C ３－７ "Cycloalkyl" and "C ３－６ "Cycloalkyl" means cycloalkyl having 3 to 7 and 3 to 6 carbon atoms, respectively, and "C ５－１２The "spirocycloalkane ring" means a spirocycloalkane ring having 5 to 12 carbon atoms. Examples of the "cycloalkane ring" include cyclobutane, cyclopentane, cyclohexane, cycloheptane, and the like.

[0043] As used herein, "cycloalkylene" refers to a divalent group derived from a cycloalkane ring. ３－６ "Cycloalkylene" refers to a cycloalkylene having 3 to 6 carbon atoms. Examples of "cycloalkylene" include, but are not limited to, cyclobutylene, cyclopentylene, cyclohexylene, and the like.

[0044] As used herein, a "cycloalkene ring" refers to a hydrocarbon ring containing at least one carbon-carbon double bond. As used herein, a "cycloalkene ring" may be a monocyclic cycloalkene, a fused bicyclic cycloalkene, or a bridged cycloalkene in which two non-adjacent atoms of the ring are connected by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. ３－７ "Cycloalkene ring" means a cycloalkene ring having 3 to 7 carbon atoms, ４－７ The term "cycloalkene ring" refers to a cycloalkene ring having 4 to 7 carbon atoms. Examples of the "cycloalkene ring" 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] As used herein, a "heterocycloalkane ring" refers to a saturated ring containing, as a ring member, one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur. As used herein, a "heterocycloalkyl" refers to 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 connected by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. As used herein, a "3- to 7-membered heterocycloalkane ring" refers to a heterocycloalkane ring having a total of 3 to 7 carbon atoms and heteroatoms as ring member atoms, a "5- to 12-membered spiroheterocycloalkane ring" refers to a spiroheterocycloalkane ring having a total of 5 to 12 carbon atoms and heteroatoms as ring member atoms, and a "3- to 7-membered heterocycloalkyl" refers to a heterocycloalkyl having a total of 3 to 7 carbon atoms and heteroatoms as ring member atoms.Examples of "heterocycloalkyl" include oxiranyl, thiaarnyl, aziridinyl, oxetanyl, thiatanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, tetrahydropyranyl, pyranyl, tetrahydrothiopyranyl, thiopyranyl, piperidinyl, 1,4-dioxanyl, 1,4-oxathianyl, morpholinyl, thiomorpholinyl, 1,4-dithia nyl, piperazinyl, 1,4-azathianyl, oxepanyl, thiepanyl, azepanyl, 1,4-dioxepanyl, 1,4-oxathiepanyl, 1,4-oxazepanyl, 1,4-dithiepanyl, 1,4-thieazepanyl, 1,4-azaphosphinanyl, 1,4-diazepanyl, 1,2-tetrahydrothiazin-2-yl, 1,3-tetrahydrothiazin-3-yl, tetrahydrothiadiazinyl, 1, 2-tetrahydrodiazin-2-yl, 1,3-tetrahydrodiazin-1-yl, tetrahydroazepinyl, chromanyl, chromenyl, isoxazolidinyl, 1,3-oxazolidin-3-yl, isothiazolidinyl, 1,3-thiazolidin-3-yl, 1,2-pyrazolidin-2-yl, 1,3-pyrazolidin-1-yl, 7-oxa-1-aza-spiro[4,4]nonanyl, 3-azabicyclo[3 .1.0]hexanyl, indolinyl, dihydroindolinyl, octahydro-1H-indolyl, octahydro-2H-pyrido[1,2-a]pyrazinyl, 3-azabicyclo[4.1.0]heptanyl, 3,4-dihydro-2H-pyranyl, 1,2,3,4-tetrahydropyridinyl, 1,2,5,6-tetrahydropyridinyl, tetrahydro-1H-benzo[d]azepinyl, and the like.

[0046] As used herein, the term "heterocycloalkene ring" refers to a ring containing one or more heteroatoms other than carbon, such as nitrogen, oxygen, and sulfur, and containing at least one double bond. The term "heterocycloalkene ring" may be a monocyclic heterocycloalkene, a fused bicyclic heterocycloalkene, a spiro ring, or a bridged heterocycloalkene in which two non-adjacent atoms in the ring are connected by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. As used herein, the term "3- to 7-membered heterocycloalkene ring" refers to 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, and dihydropyrroline.

[0047] In this specification, unless otherwise specified, the symbols:

[0048]

[0049] means that it is bonded to the other side of the paper (α-configuration), and the symbol:

[0050]

[0051] means that the molecule is bonded to the front side of the paper (β-configuration). ＊ , S ＊ The symbols (e.g., ) indicate the relative configuration of the asymmetric center. The relative configuration is represented in the structure by the symbol:

[0052]

[0053] It is expressed as:

[0054] As used herein, "pharmaceutically acceptable" means that the salt has no significant toxicity and can be used in a pharmaceutical composition. Therefore, as used herein, a "pharmaceutically acceptable salt" means that the salt has no significant toxicity and can be used in 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-benzimidazol-1-yl]piperidine-2,6-dione" means "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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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-benzimidazol-1-yl]piperidine-2,6-dione" means "(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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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-benzimidazol-1-yl]piperidine-2,6-dione" is "(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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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]quinolin-1(2H)-yl]piperidine-2,6-dione" means "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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]quinolin-1(2H)-yl]piperidine-2,6-dione" means "(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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]quinolin-1(2H)-yl]piperidine-2,6-dione" is "(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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione" means "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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione" means "(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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione" is "(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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]quinoxalin-1(2H)-yl]piperidine-2,6-dione" means "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}piperazin-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]quinoxalin-1(2H)-yl]piperidine-2,6-dione" means "(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}piperazin-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]quinoxalin-1(2H)-yl]piperidine-2,6-dione" is "(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}piperazin-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, a compound represented by the following formula (1):

[0068]

[0069] [Wherein, A is —O—, —S—, —NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxy, —CN, or 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, wherein said alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and said cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogens, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, wherein １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, —O—, —S—, —NH—, C １－３ Alkylene, C ２－３ alkenylene, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, or —OC(═O)—, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; and ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ５ is C １－６ alkyl, carboxy, hydroxy, or the following formula:

[0070]

[0071] wherein C is a group represented by １－６ Alkyl is unsubstituted or includes carboxy, hydroxy and -O-C １－６ and n is an integer of 0 to 3; or a pharmaceutically acceptable salt thereof.

[0072] In one embodiment of the present invention, A in the above formula (1) is —O—, —S—, or —CR ｂ R ｃ -, preferably -O- or -CR ｂ R ｃ -, more preferably -O- or -CF ２ -, and particularly preferably -O-.

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

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

[0075] In one embodiment of the present invention, n R １ are each independently a halogen, —O—C １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C１－３ alkyl) ２ or a 3- to 7-membered heterocycloalkyl (wherein the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms), and in another embodiment of the present invention, n R １ each independently represents a halogen atom or —O—C optionally substituted with 1 to 3 halogen atoms; １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member atom, preferably —O—C optionally substituted with 1 to 3 halogen atoms. 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 —O—C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, and more preferably —O—C １－３ It is preferably alkyl, and most preferably methoxy.

[0076] In one embodiment of the present invention, R in the above formula (1) ２ is hydrogen or C １－６ 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 the above formula (1) ３ is hydrogen or C １－６ 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 the above formula (1) ４ is unsubstituted or C ３－７ C substituted with cycloalkyl １－６ Alkyl, —C(═O)—C １－６alkyl, or 6- to 12-membered heteroaryl (the heteroaryl has 1 or 2 nitrogen atoms as ring member atoms), and in another embodiment of the present invention, R ４ is C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), preferably a C １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, or a 6-membered heteroaryl having 1 or 2 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 optionally substituted with 1 to 3 halogens. １－６ It is preferably alkyl, and most preferably 3,3,3-trifluoro-2,2-dimethylpropyl.

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

[0080] In one embodiment of the present invention, L in the above formula (1) １ is preferably a single bond, —O—, C １－３ Alkylene- or -C(=O)-, more preferably a single bond, -O-, or -CH ２ It is — or —C(═O)—, 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 the above formula (1) ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of C ３－７ a cycloalkane ring, a 3- to 7-membered heterocycloalkane ring (the heterocycloalkane ring has one or two nitrogen atoms as ring member atoms), C ３－７ In another embodiment of the present invention, the ring Q in the above formula (1) is a cycloalkene ring or a 5- to 12-membered spiroheterocycloalkane ring (the spiroheterocycloalkane ring has one or two nitrogen atoms as ring member atoms). ２ represents a benzene ring optionally substituted with one halogen atom, C ４－７ a cycloalkane ring, a C optionally substituted with one halogen atom; ４－７ 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 A cycloalkene ring, more preferably C ４－７ It is a cycloalkene ring.

[0082] In one embodiment of the present invention, R in the above formula (1) ５is preferably carboxy, or carboxy, hydroxy and —O—C １－６ C optionally substituted with 1 to 2 groups selected from the group consisting of alkyl １－６ C optionally substituted with one group selected from the group consisting of alkyl, more preferably carboxy, or carboxy and hydroxy. １－６ C optionally substituted with one group selected from the group consisting of alkyl, more preferably carboxy and hydroxy １－６ It is alkyl.

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

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

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

[0086]

[0087] [Wherein, A is —O— or —CF ２ - and R １ is a halogen, —O—C optionally substituted with 1 to 3 halogens １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member, R ２ and R ３ are each independently hydrogen or C １－６ alkyl, R ４ is C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), ring Q １ is halogen and C １－３ a benzene ring optionally having one or two groups selected from the group consisting of alkyl; 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 is a cycloalkene ring, １ represents a single bond, —O—, —CH ２ - or -C(=O)-, and ring Q ２ represents a benzene ring optionally substituted with one halogen atom, C ４－７ a cycloalkane ring, a C optionally substituted with one halogen atom; ４－７a cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, and R ５ is carboxy, hydroxy and —O—C １－６ C optionally having 1 or 2 groups selected from the group consisting of alkyl １－６ alkyl, carboxy, hydroxy, or a group represented by the formula:

[0088]

[0089] or a pharmaceutically acceptable salt thereof.

[0090] Since formula (1') corresponds to a subordinate concept of formula (1), the definitions, explanations, preferred embodiments, etc. of each group in formula (1) above all apply to each group in formula (1'). Furthermore, in this specification, when "a compound represented by formula (1)" is mentioned without any particular reservation, this means a concept that also includes "a compound represented by formula (1')", in other words, "a compound represented by formula (1) and formula (1')".

[0091] In another embodiment of the present invention, in the above formula (1′), A is —O—, and R ２ is methyl, R ３ is methyl, R ４ C optionally substituted with 1 to 3 halogen atoms １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen atom), and ring Q １ is halogen and C １－３ a benzene ring or a pyridine ring, which may have one substituent selected from the group consisting of alkyl; １ is a single bond, —O—, or —C(═O)—, and ring Q ２ is a benzene ring, C ４－７ Cycloalkane ring, or C ４－７The compound or a pharmaceutically acceptable salt thereof is provided, wherein the ring is a cycloalkene ring.

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

[0093] In yet another embodiment of the present invention, a compound selected from the group consisting of 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}pyridin-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 or a pharmaceutically acceptable salt thereof.These compounds all correspond to the compounds represented by the above formula (1) and formula (1') or pharmaceutically acceptable salts thereof.

[0094] <3. Polyfunctional 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 therefore can be used as a partial structure in a larger molecule (e.g., a polyfunctional molecule) by combining with other functional moieties. In particular, the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof specifically binds to SF-1, and therefore can be used as an SF-1 binding moiety in a larger molecule (e.g., a polyfunctional molecule) by combining with other functional moieties.

[0095] Thus, in one aspect of the present invention, there is provided a polyfunctional molecule comprising a moiety corresponding to the compound represented by formula (1) above or a pharmaceutically acceptable salt thereof.

[0096] Because the compound represented by formula (1) itself is structurally complete, when linking it to another partial structure, it is necessary to remove a specific atom or atomic group from any position in the compound. For example, when a carboxy group present at the terminal of the compound represented by formula (1) is linked to an amino group in another partial structure by dehydration condensation, the "portion corresponding to the compound represented by formula (1)" in the molecule after linking is structurally different from the compound represented by formula (1) in that the "-OH" moiety of the carboxy group has been removed. In this specification, the compound represented by formula (1) or a pharmaceutically acceptable salt thereof from which a specific atom or atomic group has been removed due to the linking reaction is referred to as the "portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof."

[0097] The linking point when linking the compound represented by formula (1) to other partial structures (for example, an E3 ligase binding moiety or a linker moiety for linking to the E3 ligase binding moiety) is not particularly limited as long as it can maintain the function of the compound represented by formula (1), in particular, the SF-1 inhibitory activity and the SF-1 binding activity. ５Therefore, in one embodiment of the present invention, the polyfunctional molecule of the present invention has a moiety corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof, which is R ５ R is directly linked to another functional moiety or linked via a linker at any point in ５ As an optional position in ５ Examples include the carboxy moiety or the amine moiety in the following formula:

[0098] In the present invention, a "multifunctional molecule" refers to a molecule containing a moiety having two or more specific functions (functionalities). As described above, the moiety corresponding to the compound of the present invention represented by formula (1) or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity or SF-1 binding activity. Therefore, the multifunctional molecule of the present invention also contains at least one other functional moiety having a specific function. When the other functional moiety is one, the multifunctional molecule of the present invention is a "bifunctional molecule." When the other functional moiety is two, three, or four, the multifunctional molecule of the present invention is a "trifunctional molecule," a "tetrafunctional molecule," or a "pentafunctional molecule," respectively. In one aspect of the present invention, the multifunctional 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 moiety may be a moiety having the same function as the moiety corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof, or may be a moiety having a different function. Thus, in one aspect of the present invention, the polyfunctional molecule is a homopolyfunctional molecule, and in another aspect, the polyfunctional molecule is a heteropolyfunctional molecule. In one aspect 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] The other functional moieties contained in the polyfunctional molecules of the present invention are not particularly limited, but are preferably those that can reasonably be expected to have beneficial effects, such as enhancing or complementing the activity of a moiety having SF-1 inhibitory / binding activity when linked to the moiety. 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, acetyltransferase-recruiting moieties, and ADCs. Furthermore, such other functional moieties may include, for example, substances useful solely for research purposes, such as specific molecular markers or radioactive labels, or functional substituents for converting the compound of Formula (1) into a prodrug.

[0100] As used herein, a "binding moiety" (e.g., an "E3 ligase-binding moiety") refers to a moiety that binds to a target (e.g., an E3 ligase), and a "recruitment moiety" (e.g., an "E3 ligase-recruitment moiety") refers to a moiety that enables recruitment of a target (e.g., an E3 ligase). Because a moiety that binds to a target can be used to recruit the target, in one aspect of the present invention, the terms "binding moiety" and "recruitment moiety" are used interchangeably.

[0101] 4. E3 Ligase Binding Moiety In the present invention, "E3 ligase" (or "E3 ubiquitin ligase") refers to a protein that recruits a ubiquitin-loaded E2 ubiquitin-conjugating enzyme, recognizes a protein substrate, and assists in or directly catalyzes the transfer of ubiquitin from the E2 protein to the substrate. A multifunctional molecule in which a moiety 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 moiety can induce the degradation of SF-1. Thus, in one aspect of the present invention, a multifunctional molecule is provided that includes a moiety corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof and another functional moiety, wherein the moiety corresponding to the compound or a pharmaceutically acceptable salt thereof is R 5In another aspect, a multifunctional molecule is provided, wherein the compound represented by formula (1) or a pharmaceutically acceptable salt thereof is linked to another functional moiety at any position in the formula (1) or ...

[0102] Targeted Protein Degradation (TPD) is a technology that uses heterobifunctional molecules, each consisting of a binder moiety that binds to a target protein (also called a "protein of interest" (POI)) and a binder moiety that binds to an E3 ligase, linked via an appropriate linker, to induce degradation of the target protein. Numerous reports have been published regarding the types of E3 ligases to be targeted in this technology, various E3 ligase-binding moieties suitable for recruiting the E3 ligase, linker structures suitable for connecting the POI and the E3 ligase-binding moiety, and technical theories for designing such linker structures (e.g., Patent Documents 1-9, Non-Patent Documents 7-9). This invention reports for the first time that such a TPD platform can actually target and induce degradation of SF-1, and in particular, presents a novel POI-binding moiety for such a TPD platform.

[0103] In the TPD platform, the POI-binding moiety and the E3 ligase-binding moiety each play a nearly independent and distinct role, and therefore, the combination of each block (part) whose respective functions have been demonstrated is likely to produce the desired effect. Therefore, the E3 ligase-binding moiety (or a combination of a ligase-binding moiety and a linker moiety) in the multifunctional molecule of the present invention can be the E3 ligase-binding moiety (or a combination of a ligase-binding moiety and a linker moiety) of any target protein degradation inducer that has been confirmed to be useful, such as the E3 ligase-binding moieties (or combinations of a ligase-binding moiety and a linker moiety) disclosed in Patent Documents 1-9 and Non-Patent Documents 7-9. Alternatively, the E3 ligase binding moiety (or a combination of a ligase binding moiety and a linker moiety) in 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 be subjected to clinical or preclinical trials, can also be used.In other words, the moiety corresponding to the compound of formula (1) of the present invention or a pharmaceutically acceptable salt thereof may be substituted with the E3 ligase binding moiety (or a combination of a ligase binding moiety and a linker moiety) of any target protein degradation inducer that has been confirmed to be useful, for example, the E3 ligase binding moieties (or a combination of a ligase binding moiety and a linker moiety) 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 moiety (or a combination of the ligase binding moiety and the linker moiety) 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 is reasonably expected that multifunctional molecules (particularly heterobifunctional molecules) with the desired SF-1 degradation activity can be obtained, although the degree of activity may vary.

[0104] Although more than 600 types of E3 ligases have been identified to date, only a limited number have been utilized in the TPD platform. The E3 ligase targeted by the multifunctional molecule of the present invention is not particularly limited. In one embodiment of the present invention, the E3 ligase targeted by the multifunctional molecule of the present invention includes 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. Examples of E3 ligase-binding moieties include CRBN, VHL, or cIAP, 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 moiety is a CRBN-binding moiety, VHL-binding moiety, cIAP-binding moiety, DCAF11-binding moiety, DCAF15-binding moiety, DCAF16-binding moiety, MDM2-binding moiety, KEAP1-binding moiety, RNF4-binding moiety, RNF114-binding moiety, AhR-binding moiety, or FEM1B-binding moiety, preferably a CRBN-binding moiety, VHL-binding moiety, or cIAP-binding moiety, more preferably a CRBN-binding moiety or VHL-binding moiety, and even more preferably a CRBN-binding moiety.

[0105] The "CRBN-binding moiety" of the present invention can be any compound moiety with any structure, as long as it exhibits the desired binding activity to CRBN. Examples of CRBN-binding moieties include those disclosed in Patent Documents 1-9 and Non-Patent Documents 7-9. For example, thalidomide and its derivatives, lenalidomide and pomalidomide, are known to exhibit binding activity to CRBN. Therefore, in one aspect of the present invention, the CRBN-binding moiety is selected from thalidomide, lenalidomide, pomalidomide, thalidomide derivatives, lenalidomide derivatives, and pomalidomide derivatives. In the present invention, the term "derivative" in the context of an E3 ligand-binding moiety refers to a moiety that has a structural difference from the parent molecule, the 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. Additionally, compounds designated as target protein degraders or proteolysis targeting chimeras (PROTACs) containing a CRBN-binding moiety, such as ARV-471, ARV-110, CFT8634, CFT7455, CFT1946, AR-LDD, NX-2127, KT-413, NX-5948, CG001419, and CFT8919, are undergoing clinical trials or preclinical trials. Thus, in one embodiment of the present invention, the CRBN-binding moiety may be the CRBN-binding moiety of these compounds.

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

[0107] In one embodiment of the present invention, the VHL-binding moiety may be 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 a derivative thereof.

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

[0109] In one aspect of the present invention, the DCAF11-binding moiety may include the ligands disclosed in S. Khan, X. et al., Nat. Med., 2019, 25, 1938-1947 or derivatives thereof.

[0110] In one aspect of the present invention, the DCAF15 binding moiety may include 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 include KB02 (G. Weng, et al., Nucleic Acids Res., 2021, 49, D1381-D1387) or a derivative thereof.

[0112] In one embodiment of the present invention, the MDM2-binding moiety may include Nutlin-3a (J.S. Lazo and E.R. 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 a derivative thereof.

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

[0114] In one embodiment of the present invention, the RNF4-binding moiety may include 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 may include 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 a derivative thereof.

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

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

[0118] In addition, the E3 ligase binding portion of the present invention is a compound represented by the formula (2) below, in which "R ６ " may also adopt any of the structures defined as "

[0119] 5. Linkers In the multifunctional molecules of the present invention, the moiety corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof may be directly linked to another functional moiety, as long as it exhibits the desired function (e.g., SF-1 inhibitory activity or SF-1 degrading activity), but is preferably linked via a linker. Thus, in one aspect of the present invention, a multifunctional molecule is provided in which the moiety corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof and another functional moiety (e.g., an E3 ligase binding moiety) are linked directly or via a linker, preferably via a linker. The linker used in the multifunctional molecules 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 degrading activity). Therefore, any linker with a structure that is reasonably expected not to impair the desired function (e.g., SF-1 inhibitory activity or SF-1 degrading activity) can be used.

[0120] As described above, in the TPD platform, it is known that the composition and length of the linker can affect the formation of the ternary complex of POI / heterobifunctional molecule / E3 ligase, the degradation-inducing activity of POI, and target selectivity. Numerous reports have been published on linker structures used in targeted protein degradation inducers, as well as technical theories for designing and optimizing them (e.g., Patent Documents 1-8, Non-Patent Documents 7-9). As described above, the present invention presents a novel POI-binding moiety that can be used in such a TPD platform. Therefore, when a linker with already proven effectiveness is used, the desired effect is likely to be achieved. Thus, in one embodiment of the present invention, the linker moiety in the multifunctional molecule of the present invention can be any linker moiety of a target protein degradation inducer that has been confirmed to be useful, such as the linker moieties disclosed in Patent Documents 1-8 and Non-Patent Documents 7-9, or the linker moieties 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, which have been reported to be subjected to clinical or preclinical trials. For example, in one embodiment of the present invention, the linker has the linker structure shown in Table 2 of Non-Patent Document 8, specifically, the linker has the following formula:

[0121]

[0122] (wherein n and m each independently represent an integer of 1 to 10). In general, it is known that when a linker that is too short is used, the efficiency of ternary complex (POI / heterobifunctional molecule / E3 ligase) formation decreases, and instead, the directivity of binary complex formation (POI / heterobifunctional molecule or heterobifunctional molecule / E3 ligase) tends to increase. On the other hand, it is known that when a linker that is too long is used, the spatial degree of freedom increases, the efficiency of ternary complex formation decreases, and the stability of the entire molecule also tends to decrease. Therefore, it is preferable to employ a linker of an appropriate length in the present invention. In view of the above, in one embodiment of the present invention, n and m in the above formula are each independently an integer of 1 to 5; in another embodiment of the present invention, n and m in the above formula are each independently an integer of 1 to 4; in yet another embodiment of the present invention, n and m in the above formula are each independently an integer of 1 to 3; and in yet another embodiment of the present invention, n and m in the above formula are each independently an integer of 1 or 2.

[0123] In the TPD platform, it is known that the binding position between the linker and the POI or the linker and the E3 ligase can also affect the ternary complex formation of the POI / heterobifunctional molecule / E3 ligase, the degradation-inducing activity of the POI, and the target selectivity. Regarding the binding position of the linker, it is generally considered important not to link the linker to the main active site of the POI binding moiety or the E3 ligase binding moiety, but to link the linker to a solvent-exposed site in the POI binding moiety or the E3 ligase binding moiety. From this perspective, in the multifunctional molecule of the present invention, the moiety corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof is preferably R ５ It is preferable that the linker is connected to any position in R ５ It is preferable that the linker is linked to the linker at the carboxyl or amine moiety in the above. Furthermore, it is preferable that the linking point between the linker and the E3 ligase binding moiety is appropriately selected from the above-mentioned viewpoints, with reference to known reports.

[0124] In one embodiment of the present invention, the linker of the present invention is "-L" defined in formula (2) below. ２ -L ３ -L ４ -" may also be used.

[0125] 6. SF-1 Degradation Inducer (SF-1 Degrader) In one embodiment of the present invention, a compound represented by the following formula (2):

[0126]

[0127] [Wherein, A is —O—, —S—, —NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxy, —CN, or 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, wherein the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogens, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, wherein １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, —O—, —S—, —NH—, C １－３ Alkylene, C ２－３ alkenylene, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, or —OC(═O)—, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; and ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; B is -L ２ -L ３ -L ４ -R ６ and L ２ is a single bond, C １－６ Alkylene, —C(═O)—, —C(═O)NH—, —(CH ２ ) ｋ-C(=O)NH- (k is an integer of 1 to 3), or -NHC(=O)-, L ３ is a single bond, C １－６ Alkylene, C ３－６ cycloalkylene, piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl; L ４ represents a single bond, -NH-, -N(-R ７ )-(R ７ is C １－６ alkyl), -CH ２ - or -C(=O)-, and R ６ 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; and n is an integer of 0 to 3, or a pharmaceutically acceptable salt thereof.

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

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

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

[0131] In one embodiment of the present invention, n R１ are each independently a halogen, —O—C １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 3- to 7-membered heterocycloalkyl (wherein the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms), and in another embodiment of the present invention, n R １ each independently represents a halogen atom or —O—C optionally substituted with 1 to 3 halogen atoms; １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member atom, preferably —O—C optionally substituted with 1 to 3 halogen atoms. 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 —O—C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, and more preferably —O—C １－３ It is preferably alkyl, and most preferably methoxy.

[0132] In one embodiment of the present invention, R in the above formula (2) ２ is hydrogen or C １－６ 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 the above formula (2) ３ is hydrogen or C １－６ 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 the above formula (2) ４ are each unsubstituted or C３－７ substituted with cycloalkyl, C １－６ Alkyl, —C(═O)—C １－６ alkyl, or 6- to 12-membered heteroaryl (the heteroaryl has 1 or 2 nitrogen atoms as ring member atoms), and in another embodiment of the present invention, R ４ is C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), preferably a C １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), more preferably 3,3,3-trifluoro-2,2-dimethylpropyl, or —C(═O)—C optionally substituted with 1 to 3 halogens. １－６ It is preferably alkyl, and most preferably 3,3,3-trifluoro-2,2-dimethylpropyl.

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

[0136] In one embodiment of the present invention, L in the above formula (2) １ is preferably a single bond, —O—, C １－３ Alkylene or —C(═O)—, more preferably a single bond, —O—, or —CH ２ It is — or —C(═O)—, 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 the above formula (2) ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of C ３－７ a cycloalkane ring, a 3- to 7-membered heterocycloalkane ring (the heterocycloalkane ring has one or two nitrogen atoms as ring member atoms), C ３－７ In another embodiment of the present invention, the ring Q in the above formula (1) is a cycloalkene ring or a 5- to 12-membered spiroheterocycloalkane ring (the spiroheterocycloalkane ring has one or two nitrogen atoms as ring member atoms). ２ represents a benzene ring optionally substituted with one halogen atom, C ４－７ a cycloalkane ring, a C optionally substituted with one halogen atom; ４－７ 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 A cycloalkene ring, more preferably C４－７ It is a cycloalkene ring.

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

[0139] In one embodiment of the present invention, L in the above formula (2) ３ is preferably piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl, more preferably piperazinediyl, piperazin-2-onediyl, 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 the above formula (2) ４ is preferably —NH—, —CH ２ - or -C(=O)-, more preferably -NH- or -C(=O)-, and even more preferably -C(=O)-.

[0141] In one embodiment of the present invention, "-L" in the above formula (2) ２ -L ３ -L ４ -" is represented by the following formula:

[0142]

[0143] (Wherein, the wavy line represents Q ２ and R ６ and the bonding position is indicated).

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

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

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

[0147]

[0148] [Wherein, A is —O— or —CF ２ - and R １ is a halogen, —O—C optionally substituted with 1 to 3 halogens １－６ Alkyl, —N(H)—C １－３ Alkyl, —N(C １－３ alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member, R ２ and R ３are each independently hydrogen or C １－６ alkyl, R ４ is C optionally substituted with 1 to 3 halogen atoms. １－６ alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens; １－６ alkyl, C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), ring Q １ is halogen and C １－３ a benzene ring optionally having one or two groups selected from the group consisting of alkyl; 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 is a cycloalkene ring, １ represents a single bond, —O—, —CH ２ - or -C(=O)-, and ring Q ２ represents a benzene ring optionally substituted with one halogen atom, C ４－７ a cycloalkane ring, a C optionally substituted with one halogen 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 is a single bond, C １－６ Alkylene, —C(═O)—, —C(═O)NH—, —(CH ２ ) ｋ -C(=O)NH- (k is an integer of 1 to 3), or -NHC(=O)-, L ３ is a single bond, C １－６ Alkylene, C ３－６ cycloalkylene, piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl; L ４represents a single bond, -NH-, -N(-R ７ )-(R ７ is C １－６ alkyl), -CH ２ - or -C(=O)-, and R ６ 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.

[0149] Since formula (2') corresponds to a subordinate concept of formula (2), the definitions, explanations, preferred embodiments, etc. of each group in formula (2) above all apply to each group in formula (2'). Furthermore, in this specification, when "a compound represented by formula (2)" is mentioned without any particular reservation, this also means a concept including "a compound represented by formula (2')", in other words, "a compound represented by formula (2) and formula (2')".

[0150] In one embodiment of the present invention, R in the above formula (2) and formula (2′) ６ is an E3 ligase binding moiety, and in another embodiment of the present invention, R ６ is the CRBN binding moiety. ６ With regard to the E3 ligase-binding portion or CRBN-binding portion that can be used as the E3 ligase-binding portion, the remarks in <3. E3 ligase-binding portion> above can be applied as they are.

[0151] In another embodiment of the present invention, R in the above formula (2) and formula (2′) ６ is the following formula:

[0152]

[0153] [In the formula, R ８ is hydrogen or C １－６ alkyl; W, X, Y, and Z are each independently a nitrogen atom, a halogen atom, or C １－６ Alkyl and —O—C １－６a carbon atom optionally bearing one group selected from the group consisting of alkyl; l, m, and n each independently represent an integer of 0 to 3; and the wavy line represents L. ４ and the bonding position is indicated.

[0154] In yet another embodiment of the present invention, R in the above formula (2) and formula (2′) ６ is the following formula:

[0155]

[0156] [In the formula, R ８ is hydrogen or C １－６ is alkyl, V is halogen, and the wavy line represents L ４ and the bonding position is indicated.

[0157] In one embodiment of the present invention, in the above formula (2) and formula (2′), R １ is —O—C optionally substituted with 1 to 3 halogens １－６ alkyl, R ４ C optionally substituted with 1 to 3 halogen atoms １－６ C optionally substituted with alkyl or one trifluoromethyl ３－６ cycloalkylmethyl, and ring Q １ is halogen and C １－６ a benzene ring optionally having one or two groups selected from the group consisting of alkyl; 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 is a cycloalkene ring, and L １ is a single bond, or —O—, or a pharmaceutically acceptable salt thereof.

[0158] In one embodiment of the present invention, in the above formula (2) and formula (2′), A is —O—, and R ２ is methyl, and R ３ is methyl, or a pharmaceutically acceptable salt thereof.

[0159] In one embodiment of the present invention, in the above formula (2) and formula (2′), R １ is methoxy, and R ４ is 3,3,3-trifluoro-2,2-dimethylpropyl, or a pharmaceutically acceptable salt thereof.

[0160] In one embodiment of the present invention, in the above formula (2) and formula (2′), ring Q １ is a benzene ring optionally having one halogen atom, and L １ is a single bond, and ring Q ２ is a cyclohexene ring, or a pharmaceutically acceptable salt thereof.

[0161] In another embodiment of the present invention, a compound of 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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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}piperazin-1-yl)carbonyl]-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-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}piperazin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinoline-1(2H)-yl}piperidine-2,6-dione2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperidin-4-yl)amino]-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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}piperazin-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}piperazin-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}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl}piperidine-2,6-dione or a pharmaceutically acceptable salt thereof. These compounds 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 in the form of a crystal. Accordingly, in one embodiment of the present invention, a crystal of the compound represented by formula (2) or a pharmaceutically acceptable salt thereof is provided. The crystal can be produced by a method known per se, or a method described in the Examples below, or a method analogous thereto.

[0163] Powder X-ray diffraction measurement of crystals may be performed by methods typically used in the art, for example, by the method described in the Examples below. Generally, the diffraction angle (2θ) in powder X-ray diffraction may vary within a range of approximately ±0.2° 2θ. For example, the lattice constant of hydrates and dehydrates may change due to the attachment and detachment of water of crystallization, which may result in a change in the diffraction angle (2θ) in powder X-ray diffraction. The intensity of the diffraction peak may also vary 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, in addition to crystals whose diffraction angles and X-ray diffraction patterns of the peaks in powder X-ray diffraction coincide, hydrates and dehydrates obtained therefrom are also included within the scope of the present invention.

[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]quinolin-1(2H)-yl]piperidine-2,6-dione The crystals are benzenesulfonate salts, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystals 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]quinolin-1(2H)-yl]piperidine-2,6-dione The crystals are ethanesulfonate salts, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystals 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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione The crystals are 10-camphorsulfonate crystals, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystals 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]quinoxalin-1(2H)-yl]piperidine-2,6-dione ethanesulfonate The crystals are ethanesulfonate salts, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystals have 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.

[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]quinoxalin-1(2H)-yl]piperidine-2,6-dione The crystals are salicylate salts, which 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 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms).

[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]quinoxalin-1(2H)-yl]piperidine-2,6-dione The crystals are crystalline benzenesulfonate salts, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystals 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]quinoxalin-1(2H)-yl]piperidine-2,6-dione The crystals are 10-camphorsulfonate crystals, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystals 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, a "pharmaceutically acceptable salt" refers to a salt that can be used as a medicine. When the compound or polyfunctional molecule of the present invention has an acidic group, it can form a basic salt (also referred to as a "base addition salt") by reacting it with a base, and when it has a basic group, it can form an acidic salt (also referred to as an "acid addition salt") by reacting it with an acid. Therefore, in one aspect of the present invention, a pharmaceutically acceptable salt of a compound represented by formula (1) or formula (2) is a basic salt, and in another aspect of the present invention, a pharmaceutically acceptable salt of a compound represented by formula (1) or formula (2) is an acidic salt.

[0172] Suitable examples of the "basic salt" in the present invention include alkali metal salts such as sodium salt, potassium salt, and lithium salt; alkaline earth metal salts such as magnesium salt and calcium salt; 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; and amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamic acid salt, and aspartic acid salt.

[0173] Suitable examples of the "acid salt" in the present invention include inorganic acid salts such as hydrohalides (e.g., hydrofluoride, hydrochloride, hydrobromide, hydroiodide), nitrates, perchlorates, sulfates, phosphates, etc.; lower alkanesulfonates (e.g., methanesulfonate, trifluoromethanesulfonate, ethanesulfonate), arylsulfonates (e.g., benzenesulfonate, p-toluenesulfonate), organic acid salts (e.g., acetate, malate, fumarate, succinate, citrate, ascorbate, tartrate, oxalate, maleate), etc.; and amino acid salts (e.g., glycine salt, lysine salt, arginine salt, ornithine salt, glutamate, aspartate).

[0174] The compound of the present invention or a pharmaceutically acceptable salt thereof may take up water molecules and become a hydrate when left in the air or recrystallized, and such hydrates are also included in the present invention. Furthermore, the compound of the present invention or a pharmaceutically acceptable salt thereof may absorb a certain solvent when left in a solvent or recrystallized, and become a solvate, and such solvates are also included in the present invention. Furthermore, the compound of the present invention or a pharmaceutically acceptable salt thereof may exist as an amorphous or crystalline form.

[0175] In addition, the compound of the present invention or a pharmaceutically acceptable salt thereof may be labeled with one or more pharmaceutically acceptable radioactive or non-radioactive isotopes. Examples of isotopes that can be incorporated into the compound of the present invention or a pharmaceutically acceptable salt thereof include isotopes of hydrogen, carbon, nitrogen, oxygen, and fluorine, for example, ２ H. ３ H. １１ C. １３ C. １４ C. １３ N. １５ N. １５ O. １７ O. １８ O, and １８ Examples of isotopically labeled compounds include, but are not limited to, F. Radioactive or non-radioactive labeled compounds may be useful to help determine or measure the effectiveness of compounds of the invention, for example, by characterizing their site or mode of action, or binding affinity to a pharmacologically important site of action. Such isotopically 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 solvates thereof may exist in various isomers, such as geometric isomers such as cis- and trans-isomers, tautomers, rotational isomers, and optical isomers (including enantiomers and diastereomers) such as d- and l-isomers, depending on the types and combinations of substituents. Unless otherwise specified, the compounds of the present invention include all such isomers and stereoisomers, as well as mixtures of these isomers and stereoisomers in any ratio. Mixtures of these isomers can be separated by known resolution methods.

[0177] The present invention also encompasses prodrugs of the compounds represented by formula (1) or (2). A prodrug is a compound having a group that can be converted into an amino group, a hydroxy group, a carboxy group, or the like of the compound 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 specific examples of the prodrug include: (1) when the compound has an amino group, the amino group is acylated, alkylated or phosphorylated (for example, a compound in which the amino group is eicosanoylated, alanylated, pentylaminocarbonylated, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxycarbonylated, tetrahydrofuranylated, pyrrolidylmethylated, pivaloyloxymethylated or tert-butylated), and (2) when the compound has a hydroxyl group, the hydroxyl group is acylated, alkylated, phosphorylated or borated (for example, a compound in which the hydroxyl group is acetylated, palmitoylated, propanoylated, pivaloylated, succinylated, fumarylated, alanylated or dimethylaminomethylcarbonylated), and (3) When the compound has a carboxy group, examples thereof include compounds in which the carboxy group is esterified or amidated (for example, compounds in which the carboxy group is ethyl-esterified, phenyl-esterified, carboxymethyl-esterified, dimethylaminomethyl-esterified, pivaloyloxymethyl-esterified, ethoxycarbonyloxyethyl-esterified, amidated, or methylamidated).

[0178] 8. Compositions and Pharmaceutical Uses In one aspect of the present invention, there is provided a composition for inhibiting SF-1, a composition for inducing the degradation of SF-1, or a pharmaceutical composition containing the compound represented by the above formula (1) or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a moiety corresponding to the compound or a pharmaceutically acceptable salt thereof, or a compound represented by the above formula (2) or a pharmaceutically acceptable salt thereof, or a crystal thereof. In another aspect of the present invention, there is provided a method for treating a disease, comprising administering to a subject in need of such treatment an effective amount of the compound represented by the above formula (1) or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a moiety corresponding to the compound or a pharmaceutically acceptable salt thereof, or the compound represented by the above formula (2) or a pharmaceutically acceptable salt thereof, or a crystal thereof. In yet another aspect of the present invention, there is provided a compound represented by the above formula (1) or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a moiety corresponding to the compound or a pharmaceutically acceptable salt thereof, or the compound represented by the above formula (2) or a pharmaceutically acceptable salt thereof, or a crystal thereof, for use in the treatment of a disease. Additionally, in yet another aspect of the present invention, there is provided a compound represented by the above formula (1) or a pharmaceutically acceptable salt thereof, a polyfunctional molecule containing a moiety corresponding to the compound or a pharmaceutically acceptable salt thereof, or a compound represented by the above formula (2) or a pharmaceutically acceptable salt thereof, or a crystal thereof, for use in the manufacture of a medicament for treating a disease.

[0179] In the present invention, the term "composition for inhibiting SF-1" refers to a composition intended to inhibit SF-1. Inhibition of SF-1 typically refers to inhibiting the physiological activity of SF-1, particularly blocking or attenuating the expression of genes transcriptionally controlled by SF-1. Examples of SF-1 inhibition include direct binding to SF-1 to block or attenuate the transcription-inducing activity of downstream genes by SF-1. Other examples include compositions that act on upstream proteins of SF-1 without directly binding to SF-1, thereby blocking or attenuating the physiological activity of SF-1. "Compositions for inhibiting SF-1" include not only compositions intended solely to inhibit SF-1, but also those that include SF-1 inhibition as one of their purposes. "Compositions for inhibiting SF-1" typically include compositions that list SF-1 inhibition as one of their intended uses in the accompanying leaflet, packaging, promotional materials, etc., but also include compositions that essentially include SF-1 inhibition as one of their intended uses, even if such a use is not explicitly stated.

[0180] In the present invention, "a composition for inducing the degradation of SF-1" means a composition intended to induce the degradation of SF-1. "A composition for inducing the degradation of SF-1" includes not only compositions intended solely to induce the degradation of SF-1, but also those that include the induction of SF-1 degradation as one of their purposes. "A composition for inducing the degradation of SF-1" typically includes those for which the induction of SF-1 degradation is listed as one of the uses in the attached instructions, packaging, promotional materials, etc. of the composition, but also includes those that essentially include the induction of SF-1 degradation as one of their uses, even if there is no such explicit indication.

[0181] In the present invention, the term "pharmaceutical composition" refers to 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 compositions for the treatment and / or prevention of diseases in which SF-1 is involved in the development or progression of the disease. Examples of such diseases include, but are not limited to, castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, cancers such as breast cancer, Cushing's syndrome, and primary aldosteronism. Thus, in one aspect of the present invention, the pharmaceutical composition of the present invention is for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, cancers such as breast cancer, Cushing's syndrome, or primary aldosteronism. In a further aspect of the present invention, the pharmaceutical composition of the present invention is for treating castration-resistant prostate cancer or adrenocortical carcinoma. In another aspect of the present invention, the pharmaceutical composition of the present invention is for treating castration-resistant prostate cancer. In yet another aspect of the present invention, the pharmaceutical composition of the present invention is for treating adrenocortical carcinoma.

[0182] The route of administration of such a composition to humans or other animals may be any of oral administration using tablets, pills, capsules, granules, powders, liquids, etc., or parenteral administration using intra-articular, intravenous, intramuscular, etc. injections, suppositories, eye drops, eye ointments, transdermal liquids, ointments, transdermal patches, transmucosal liquids, transmucosal patches, inhalants, etc. However, considering that the molecular weight of the compound or polyfunctional molecule 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, granules, 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, polyvinylpyrrolidone, magnesium aluminometasilicate, etc. Such solid compositions may 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 be coated with a sugar coating or a film of a gastric or enteric substance, if necessary.

[0184] Liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, etc. A commonly used inert diluent, such as purified water or ethanol, can be added to such liquid compositions. In addition to the inert diluent, such liquid compositions may contain auxiliary agents such as solubilizers and wetting agents, sweeteners, flavors, fragrances, preservatives, etc.

[0185] Injectable preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, emulsions, etc. Aqueous solvents include, for example, distilled water for injection and physiological saline. Non-aqueous solvents include, for example, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, and polysorbate 80. Such injectable compositions may further contain an isotonicity agent, a preservative, a wetting agent, an emulsifier, a dispersant, a stabilizer, a solubilizing agent, etc. These injectable compositions can be sterilized, for example, by filtration through a bacteria-retaining filter, addition of a sterilizing agent, or irradiation. Alternatively, these injectable compositions can be prepared as sterile solid compositions, which can be dissolved or suspended in sterile water or a sterile injectable solvent prior to use.

[0186] Examples of topical preparations include ointments, plasters, creams, jellies, poultices, sprays, lotions, eye drops, and eye ointments. These topical preparations may contain commonly used ointment bases, lotion bases, aqueous or non-aqueous liquids, suspensions, emulsions, and the like. Examples of ointment or lotion bases include polyethylene glycol, propylene glycol, white petrolatum, white beeswax, polyoxyethylene hydrogenated castor oil, glycerin monostearate, stearyl alcohol, cetyl alcohol, lauromacrogol, and sorbitan sesquioleate.

[0187] Transmucosal preparations, such as inhalants and nasal preparations, may be solid, liquid, or semisolid and may be prepared according to conventional methods. For example, known excipients, as well as pH adjusters, preservatives, surfactants, lubricants, stabilizers, thickeners, etc., may be added as appropriate. These transmucosal preparations can be administered using a suitable inhalation or insufflation device. For example, known devices such as metered-dose inhalers or nebulizers can be used to administer the compound or polyfunctional molecule alone or as a powder of a formulated mixture, or as a solution or suspension in combination with a pharmaceutically acceptable carrier. Dry powder inhalers and the like may be for single or multiple administrations, and can use dry powder or powder-containing capsules. Alternatively, a suitable propellant can be used. For example, the preparation may be in the form of a pressurized aerosol spray using a suitable gas, such as a chlorofluoroalkane, a 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. Such combinations may be administered simultaneously, or separately, consecutively, or at a desired time interval. Simultaneous administration preparations may be formulated as a combined preparation or separately.

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

[0190] In the present invention, "effective amount" or "therapeutically effective amount" means an amount effective for treating, preventing the progression of, or alleviating existing symptoms of a subject being treated. The effective amount can be appropriately determined according to conventional methods, taking into account the desired therapeutic effects and side effects.

[0191] 9. Combination Use The compound of the present invention or a pharmaceutically acceptable salt thereof, polyfunctional molecule, composition for inhibiting SF-1, composition for inducing degradation of SF-1, or pharmaceutical composition 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 the alkylating agent include alkylating agents such as nitrogen mustard, nitrogen mustard-N-oxide, and chlorambucil; aziridine alkylating agents such as carboquone and thiotepa; epoxide alkylating agents such as dibromomannitol and dibromodalcitol; nitrosourea alkylating agents such as carmustine, lomustine, semustine, nimustine hydrochloride, streptozocin, chlorozotocin, and ranimustine; busulfan; improsulfan tosylate; and dacarbazine.

[0193] Examples of the various antimetabolites include purine antimetabolites such as 6-mercaptopurine, 6-thioguanine, and thioinosine; pyrimidine antimetabolites such as fluorouracil, tegafur, tegafur-uracil, carmofur, doxifluridine, broxuridine, cytarabine, enocitabine, and capecitabine; folate antimetabolites such as methotrexate, trimetrexate, and pemetrexed; and active folate agents such as levofolinate.

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

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

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

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

[0198] Examples of hormone agents include hydrocortisone, cortisone acetate, fludrocortisone, fludrocortisone acetate, dexamethasone, methylprednisolone, prednisolone, prasterone, betamethasone, triamcinolone, oxymetholone, nandrolone, methenolone, fosfestrol, ethinyl estradiol, chlormadinone, glucocorticoids, medroxyprogesterone, bicalutamide, enzalutamide, apalutamide, grollutamide, flutamide, anastrozole, exemestane, letrozole, abiraterone, goserelin, leuprorelin, toremifene, degarerx, mitotane, and tamoxifen.

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

[0200] Examples of anti-tumor antibodies and molecularly targeted drugs include anti-tumor antibodies (including modified forms thereof) such as trastuzumab, rituximab, cetuximab, pertuzumab, nimotuzumab, pembrolizumab, camrelizumab, denosumab, bevacizumab, infliximab, and ramucirumab; kinase inhibitors such as imatinib, gefitinib, erlotinib, sunitinib, lapatinib, eganelisib, 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, aceglatone, sizofiran, picibanil, procarbazine, pipobroman, neocarzinostatin, hydroxyurea, ubenimex, and krestin.

[0202] Furthermore, 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 used in combination with antibody-drug conjugates (ADCs) containing the above-mentioned other antitumor agents as payloads, or targeted protein degradation inducers having the above-mentioned other antitumor agents as POI ligands.

[0203] The compound of the present invention or a pharmaceutically acceptable salt thereof, a polyfunctional molecule, a composition for inhibiting SF-1, a composition for inducing the degradation of SF-1, or a pharmaceutical composition may be administered simultaneously with or separately from the above-mentioned concomitant drug, and may be formulated as a combined drug or kit.

[0204] In the treatment of adrenocortical carcinoma, antitumor agents that can be suitably used in combination with the compound of the present invention or a pharmaceutically acceptable salt thereof, polyfunctional molecule, composition for inhibiting SF-1, composition for inducing the degradation of SF-1, or pharmaceutical composition include one or more selected from 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 eganelisib, apatinib, cabozantinib, and OR-449; mitotane; and etoposide.

[0205] In the treatment of castration-resistant prostate cancer, antitumor agents that can be suitably used in combination with the compound of the present invention or a pharmaceutically acceptable salt thereof, polyfunctional molecule, composition for inhibiting SF-1, composition for inducing the degradation of SF-1, or pharmaceutical composition include one or more selected from hormonal agents such as abiraterone, enzalutamide, grollutamide, apalutamide, etc.; microtubule inhibitors such as docetaxel, cabazitaxel, etc.; PARP inhibitors such as olaparib, rucaparib, etc.; androgen receptor degradation inducers such as ARV-110, ARV-766, CC-94676, etc.; CYP11A1 enzyme inhibitors such as ODM-208; and antitumor antibodies such as nivolumab, pembrolizumab, camrelizumab, etc.

[0206] <10. Novel Intermediate> In one embodiment of the present invention, a novel intermediate is prepared by reacting a compound represented by the following formula (10):

[0207]

[0208] [Wherein, A is —O—, —S—, —NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxy, —CN, or C １－６Alkyl, 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, wherein said alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and said cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogens, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, wherein １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, —O—, —S—, —NH—, C １－３ Alkylene, C ２－３ alkenylene, —C(═O)—, —C(═O)NH—, —NHC(═O)—, —C(═O)O—, or —OC(═O)—, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; and ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R １０ is C １－６ alkyl, wherein said C １－６ wherein the alkyl is substituted with one or two 3- to 7-membered heterocycloalkyls, the heterocycloalkyl has one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, and the heterocycloalkyl is unsubstituted or substituted with an amino-protecting group, and n is an integer of 0 to 3, or a pharmaceutically acceptable salt thereof.

[0209] The compound of formula (10) of the present invention can be used as a production intermediate for the compound of formula (2) or formula (2') of the present invention, or is useful as a production intermediate, as will be described in detail in the following general production method and examples. The compound of formula (10) of the present invention is １０ The compound is the same as the compound of formula (1) except that the definition of each group in formula (1) is different from that of the compound of formula (1). Therefore, the definition, explanation, preferred embodiment, etc. of each group in formula (1) are the same as those in formula (1). ５ All of the above also apply to each group in formula (10), except for the one regarding

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

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

[0212] <11. General Production Methods> Representative production methods for the compounds of the present invention or pharmaceutically acceptable salts thereof are described below. The compounds of the present invention can be produced by various production methods. The production methods described below, as well as the Reference Examples and Examples described below, are merely examples, and the present invention should not be construed as being limited thereto. Each raw material compound may form a salt as long as it does not inhibit the reaction. Examples of such salts include the same salts as the pharmaceutically acceptable salts of the compounds described above. Unless a specific production method is described, the raw material compounds may be readily available commercially or may be produced by known methods or methods equivalent thereto. In addition, the production intermediates produced in the following production methods may be isolated and purified by methods such as column chromatography (including normal and reverse phase) using silica gel, alumina, etc., recrystallization, reprecipitation, distillation, etc., or may be used directly in the next reaction without isolation and purification. The contents of all patent documents, non-patent documents, and reference documents explicitly cited herein are incorporated herein by reference. The compounds, their pharmaceutically acceptable salts, and their production intermediates can be produced by applying various known production methods, utilizing characteristics based on their basic skeletons or the types of substituents. Known methods include those described in, for example, "ORGANIC FUNCTIONAL GROUP PREPARATIONS," 2nd ed., ACADEMIC PRESS, INC., 1989, and "Comprehensive Organic Transformations," 2nd ed., VCH Publishers Inc., 1999. Depending on the type of functional group present in the compound, it may be effective in terms of production technology to protect the functional group with an appropriate protecting group at the raw material or intermediate stage, or to replace the functional group with a group that can be easily converted to the functional group. Examples of such functional groups include amino groups, hydroxy groups, formyl groups, carbonyl groups, and carboxy groups. Protecting groups for these groups include, for example, those described in P.G. Wuts, "Protective Groups in Organic Synthesis," 5th ed., Wiley, 2014.The protecting group or the group that can be easily converted into the functional group can be appropriately selected and used depending on the reaction conditions of the manufacturing method for producing the compound. According to such a method, the desired compound can be obtained by introducing the group and performing a reaction, and then removing the protecting group or converting it into the desired group as necessary. A prodrug of a compound can be produced by introducing a specific group into a raw material or intermediate, or by performing a reaction using the resulting compound, similar to the above-mentioned protecting groups. The reaction for producing a prodrug can be carried out by applying a method known to those skilled in the art, such as ordinary esterification, amidation, dehydration, or hydrogenation. Furthermore, functional group conversion or the use of a protecting group in a manufacturing intermediate used in each step of the following method can be carried out by a known method or a method similar thereto, or a method described in the Examples below or a method similar thereto. In the description of the general manufacturing method below, symbols used in the formulae without a definition have the same meaning as above.

[0213] A general method for producing the compound of formula (1) of the present invention will be described below. In the following description, the following abbreviations may be used: 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 registration number: 1445085-77-7); BrettPhos Pd G3: [(2-dicyclohexylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)]palladium(II) methanesulfonate (CAS Registry Number: 1470372-59-8) Tf: Trifluoromethanesulfonyl group SEM: 2-(trimethylsilyl)ethoxymethyl group XantPhos: 4,5-bis(diphenylphosphino)-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 C optionally substituted with 1 to 3 halogen atoms １－６ C optionally substituted with an alkyl group or one trifluoromethyl group ３－６ Compound a12, R ４ C optionally substituted with 1 to 3 halogen atoms １－６ Compound a11, which is an alkylcarbonyl group, and R ４Compound a14, in which R is a 6-membered heteroaryl group having one or two nitrogen atoms as ring atoms (the heteroaryl group may be substituted with one halogen atom), can be produced by the following method. Although general production methods for each reaction site are shown in order, the respective steps do not necessarily have to be carried out in the order shown below as long as they do not affect the reaction substrates and reaction products.

[0215]

[0216] [In the formula, Pg １ is a protecting group for a carboxy group (e.g., a methyl group, an ethyl group, a benzyl group, or a tert-butyl group), M is a metal or a metal halide (e.g., a magnesium halide, a lithium halide, or a zinc halide), R ａ１ is C optionally substituted with 1 to 3 halogen atoms １－６ C optionally substituted with an alkyl group or one trifluoromethyl group ３－６ is a cycloalkyl group, R ａ２ is the following formula:

[0217]

[0218] R is a substituent represented by Ｘ is R ５ , or R ５ R is a group that can be converted into ａ３ is a 6-membered heteroaryl group having one or two nitrogen atoms as ring atoms (the heteroaryl group may be substituted with one halogen atom).

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

[0220] The second step is a step of 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 with compound a4 in a solvent such as THF in the presence of a copper reagent such as copper(II) bromide. The reaction temperature is preferably from -78°C to room temperature.

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

[0222] The fourth step is a step of reducing the cyano group of compound a6 to obtain compound a7. 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 under heating in a solvent such as THF.

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

[0224] The sixth step is a step of condensing 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 be carried out by reacting compound a10 with oxalyl chloride or the like in a solvent such as dichloromethane to obtain an acid chloride, which is then reacted with compound a9 in a solvent such as dichloromethane in the presence of a base such as DIPEA.

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

[0226] Step eight is a step of obtaining compound a14 from compound a9 and compound a13 by Buchwald amination or aromatic nucleophilic substitution. The Buchwald amination in this step can be carried out, for example, 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 in this step can be carried out, for example, 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 is expressed by the following formula:

[0228]

[0229] In the case of a group represented by ５ The site can be introduced according to known methods, including, but not limited to, WO 2013088315 A1 and WO 2020192588 A1.

[0230] R ５is expressed by the following formula:

[0231]

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

[0233] R ５ is expressed by the following formula:

[0234]

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

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

[0237]

[0238] [In the formula, R ｂ１ is a single bond or a hydroxy group, C １－６ C optionally having a group selected from the group consisting of an alkoxy group, a piperazinyl group, and a 1-tert-butoxycarbonylpiperazinyl group １－６ is an alkylene group, and Pg １ is a protecting group for a carboxy group.

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

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

[0241]

[0242] [In the formula, R ｃ１ represents a single bond, or a carboxy group, a hydroxy group, and C １－６ C optionally having a substituent selected from the group consisting of alkoxy groups １－６ is an alkylene group, and Pg １ is a protecting group for a carboxy group, and Pg ２ is a protecting group for an amino group, and X ｃ is a leaving group.

[0243] The first step is a step of reducing the ester of compound c1 to obtain compound c2. 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 is a step of converting the hydroxy group of compound c2 into a leaving group to obtain compound c3. Examples of the leaving group in this step include a methanesulfonyloxy group and a p-toluenesulfonyloxy group, and the leaving group can be converted by a commonly used method (reagents, solvents, reaction conditions, etc.).

[0245] The third step is a step of obtaining compound c5 from compound c3 and compound c4 by 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 remove the protecting group Pg of the amino group of compound c5. ２The deprotection reaction in this step can be carried out by a method commonly used for deprotecting an amino group. For example, Pg ２ In the case of a tert-butoxycarbonyl group, the conversion can be carried out by reacting Compound c5 with hydrogen chloride, an acid such as trifluoroacetic acid, etc. in a solvent such as dichloromethane.

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

[0248]

[0249] [In the formula, Pg ３ is a protecting group for a hydroxy group (e.g., a methyl group, a benzyl group, a methoxymethyl group, etc.), Lg is a leaving group, R ｄ１ is the following formula:

[0250]

[0251] or a group convertible into said group, ｄ２ is 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, ｄ３ is C optionally substituted with 1 to 3 halogen atoms １－６ is an alkyl group.

[0252] The first step is to form a protecting group Pg ３ The deprotection reaction in this step can be carried out by a method commonly used for deprotecting a hydroxyl group. 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 a step of obtaining compound d3 from compound d2 by triflation of the hydroxy group. The triflation reaction in this step can be carried out, for example, by reacting compound d2 with a triflating agent such as trifluoromethanesulfonic anhydride in a solvent such as dichloromethane in the presence of a base such as pyridine.

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

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

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

[0257]

[0258] wherein R is a group represented by the following formula:

[0259]

[0260] M is a dihydroxyboryl group, a pinacolatoboryl group, or the like; R Ｘ is R ５ Or, R ５ is a group that can be converted to

[0261] The first step is a step of converting carboxylic acid e1 to acid chloride e2. The chlorination reaction in this step 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 is a coupling reaction between compound e2 and compound e3 to obtain compound e4. The coupling reaction in this step can be carried out, for example, by reacting compound e2 with 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(0). Literature examples of the coupling reaction in this step include Catalysts, 2019, 9(1), 53.

[0263] Next, equation (3):

[0264]

[0265] [In the formula, R Ｘ is R ５ , or R ５ The method for producing a starting compound represented by the formula:

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

[0267]

[0268] [In the formula, R ｆ１ａ , R ｆ１ｂ , R ｆ１ｃ , and R ｆ１ｄ are each independently a hydrogen atom, a halogen atom, or C １－６ is an alkyl group, R ｆ２ is OH or a leaving group, where R ｆ２ In the case of OH, R ｆ３ is OH or a leaving group, or Rｆ２ is a leaving group, R ｆ３ is OH, and Y １ is a halogen atom, a trifluoromethanesulfonyloxy group, a pinacolatoboryl group, or a dihydroxyboryl group, １ is a halogen atom or a trifluoromethanesulfonyloxy group, Y ２ is a pinacolatoboryl group or a dihydroxyboryl group, or Y １ is a pinacolatoboryl group or a dihydroxyboryl group, Y ２ is a halogen atom or a trifluoromethanesulfonyloxy group, Pg １ is a protecting group for a carboxy group, and R Ｘ is R ５ , or R ５ is a group that can be converted to

[0269] The first step is a step of obtaining compound f3 from compound f1 and compound f2. ｆ２ is OH and R ｆ３ When R is OH, this reaction can be carried out by 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 azodicarboxylate such as diisopropyl azodicarboxylate in a solvent such as THF. ｆ２ or R ｆ３ In the case where the nucleophilic substitution reaction is a leaving group, the 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 Compounds f1 and 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 a step of obtaining 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 in the presence of 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 a step of obtaining compounds f9 and f10 by the Mitsunobu reaction of compounds f7 and 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 in a solvent such as toluene under heating.

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

[0273] The fifth step is a step of obtaining compound f12 from compound f11 by oxidation. 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-benziodoxol-3-(1H)-one or manganese(IV) oxide in a solvent such as dichloromethane.

[0274] Compound f13 can also be obtained from compound f10 through the same steps as in the fourth and fifth steps of this method.

[0275] A general method for producing the compound of formula (2) of the present invention will be described below.

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

[0277]

[0278] [In the formula, R ６’ is the following formula:

[0279]

[0280] R is any group selected from the groups represented by ６’’ is a protecting group for imide (e.g., (2-trimethylsilylethoxy)methyl group, tert-butoxycarbonyl group, benzyloxymethyl group, etc.), and Q ３ is the following formula:

[0281]

[0282] Pg １ is a protecting group for a carboxy group (e.g., a methyl group, an ethyl group, a tert-butyl group, etc.).

[0283] R ６’ is expressed by the following formula:

[0284]

[0285] In the case where the protecting group is a group represented by the formula:

[0286] The deprotection reaction in this step can be carried out by a method commonly used for deprotecting a protecting group for a nitrogen atom of an imide. For example, when 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 the resulting compound with a base such as N,N'-dimethylethylenediamine in a solvent such as ethyl acetate.

[0287] R ６’ is expressed by the following formula:

[0288]

[0289] When the group is any group selected from the following, this step can be carried out by a cyclization reaction.

[0290] The cyclization reaction in this step is carried out by Pg １ When Pg is a tert-butyl group, the cyclization 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. １When is a methyl group or an ethyl group, the reaction can be carried out, for example, by reacting compound (4) with a base such as potassium tert-butoxide in a solvent such as THF.

[0291] R ６’ is expressed by the following formula:

[0292]

[0293] In the case where the group is represented by the formula:

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

[0295] Next, equation (4):

[0296]

[0297] The method for producing the starting compound represented by the formula:

[0298] (Method H) Among the raw material compounds (4), L ４ Compound h4, in which is —C(═O)—, can be prepared according to the following method.

[0299]

[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 has the same meaning as above, and L ３ is a piperazinediyl group, a piperazin-2-onediyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediyl group, and X ｈ is a halogen atom.

[0301] The first step is a step of converting compound h1 to 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 Registry 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 with 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 raw material compounds (4), L ４ Ga-CH ２ Compound i4, which is -, can be prepared according to the following method.

[0304]

[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 has the same meaning as above, and L ３ is a piperazinediyl group, a piperazin-2-onediyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediyl group, and X ｉ is a halogen atom.

[0306] The first step is a formylation reaction to convert compound i1 to compound i2. 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. The addition of saccharin to this reaction may be preferable.

[0307] The second step is a step of obtaining compound i4 from compound i2 and compound i3 by reductive amination. The reductive amination 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. Alternatively, the reductive amination in this step can be carried out, for example, by using a Dean-Stark apparatus to react compound i3 with compound i2 under heating in a solvent such as toluene, to obtain an imine, and then reacting the resulting imine with a reducing agent such as sodium borohydride in a solvent such as methanol.

[0308] (Method J) Among the raw material compounds (4), L ２ Compound j3, in which C=O, can be prepared according to the following method.

[0309]

[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 has the same meaning as above, and L ３ is a piperazinediyl group, a piperazin-2-onediyl 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 is a step of condensing compound j1 and compound j2 to obtain compound j3. The condensation reaction in this step 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, the condensation reaction in this step can 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 to obtain an acid chloride, and then reacting the resulting acid chloride with compound j2 in a solvent such as dichloromethane in the presence of a base such as DIPEA.

[0312] L ２ is CONH, or (CH ２ ) ｎ A compound CONH (n is an integer of 1 to 3) can be obtained under similar conditions by changing compound j1 and compound j2 to the corresponding carboxylic acid and amine, respectively.

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

[0314] (Method K) Among the raw material compounds (4), L ２ But -CH ２ Compound k3, which is -, can be prepared according to the following method.

[0315]

[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 has the same meaning as above, and L ３ is a piperazinediyl group, a piperazin-2-onediyl 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 is a step of obtaining compound k3 from compound k1 and compound k2 by reductive amination. The reductive amination in this step can be carried out under the same conditions as in the second step of Method I.

[0318] L ２ But C ２－６ A compound having an alkylene group can also be obtained under similar conditions by changing compound k1 to the corresponding aldehyde.

[0319] (Method L) Among the raw material compounds (4), Q ２ is a benzene ring optionally substituted with one halogen atom, and L ２ Compound 16, in which is —NHCO—, can be prepared according to the following method.

[0320]

[0321] [In the formula, X ｌ is a halogen atom, Pg ２ is a protecting group for an amino group, R ｌ１ is the following formula:

[0322]

[0323] R is a group represented by ｌ２ａ , R ｌ２ｂ , R ｌ２ｃ , and R ｌ２ｄ are each independently a hydrogen atom or a halogen atom, and R ｌ３ is the following formula:

[0324]

[0325] or a group that can be converted into said group.]

[0326] The first step is a step of obtaining compound l3 by Buchwald amination from compound l1 and compound l2. The amination reaction in this step can be carried out by reacting compound l1 with compound l2 under heating in a solvent such as tert-butyl alcohol or DMSO in the presence of a ligand such as 1,2,3,4,5-pentaphenyl-1'-(di-tert-butylphosphino)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]dec-5-ene.

[0327] The second step is to add the protecting group Pg ２ This is a step of converting compound 13 into compound 14 by a deprotection reaction of the formula (I). The deprotection reaction in this step can be carried out by a method commonly used for deprotecting an amino group. For example, Pg ２ When is a tert-butoxycarbonyl group, the reaction can be carried out by reacting compound 13 with an acid such as hydrochloric acid in a solvent such as dichloromethane.

[0328] The third step is a step of condensing compound 14 with compound 15 to obtain compound 16. The condensation reaction in this step can be carried out under the same conditions as in the first step of Method J.

[0329] The fourth step is a step of obtaining compound 16 from compound 14 and compound 17 by a urea reaction. The urea reaction in this step can be carried out by reacting compound 14 with triphosgene in a solvent such as dichloromethane in the presence of a base such as triethylamine or pyridine to obtain a carbamoyl chloride, and then reacting the resulting carbamoyl chloride with compound 17 in a solvent such as dichloromethane in the presence of a base such as triethylamine.

[0330] Next, equation (5):

[0331]

[0332] [In the formula, R Ｘ is the following formula:

[0333]

[0334] The present invention also shows a method for producing a starting compound represented by the following formula:

[0335] Among the raw material compounds (5), L ２ is C=O, CONH, (CH ２ ) ｎ The compound CONH (n is an integer of 1 to 3) or NHCO can be produced by the same method as in Method J. ２ But C １－６ Compounds having an alkylene group can be produced by a method similar to Method K.

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

[0337]

[0338] [In the formula, L ３ is a piperazinediyl group, a piperazin-2-onediyl 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 (e.g., a bromine atom, an iodine atom, a chlorine atom, a methanesulfonyloxy group, a paratoluenesulfonyloxy group, a trifluoromethanesulfonyloxy group, etc.), R ｍ１ is the following formula:

[0339]

[0340] (wherein n is an integer of 0 to 5), １ is a protecting group for a carboxy group, R Ｘ is the following formula:

[0341]

[0342] is a group that can be converted into a group represented by the following formula:

[0343] The first step is a step of reducing the ester group of compound m1 to obtain compound m2. 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 a step of converting the hydroxy group of compound m2 into a leaving group to obtain compound m3. Examples of the leaving group in this step include a bromine atom, an iodine atom, a chlorine atom, a methanesulfonyloxy group, a paratoluenesulfonyloxy group, and a trifluoromethanesulfonyloxy group. The conversion into a leaving group can be carried out by a commonly used method (reagent, solvent, reaction conditions, etc.).

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

[0346] Next, equation (6):

[0347]

[0348] [In the formula, R ｙ is the following formula:

[0349]

[0350] The present invention also provides a method for producing a starting compound represented by the following formula:

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

[0352] Methods N to P are described below as examples of methods for producing the starting compound (6), but the synthesis method for the starting compound (6) is not limited to these.

[0353] (Method N) Among the raw material compounds (6), Q ３ is expressed by the following formula:

[0354]

[0355] Compound n8, which is any group selected from the following, can be produced according to the following method.

[0356]

[0357] [In the formula, Y １ is a halogen atom, and Y ２ is a halogen atom, a dihydroxyboryl group, a pinacolatoboryl group, or the like, and R ｎ１ａ and R ｎ１ｂ are each independently a hydrogen atom or a halogen atom, ２ is a protecting group for an amino group, and n is an integer of 1 or 2.

[0358] The first step is a reaction to convert compound n1 to 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, or N-iodosuccinimide in a solvent such as DMF.

[0359] The second step is a step of urea-forming compound n2 using compound n3 to obtain compound n4. The urea-forming 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 of obtaining compound n5 by cyclization of compound n4. The cyclization 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 80°C to 160°C.

[0361] The fourth step is a step of obtaining 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 or cesium carbonate. ２ is a pinacolatoboryl group or the like, this step can be carried out by a Chang-Lam-Evans coupling reaction. The Chang-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 to prepare a protecting group Pg ２ This is a process for converting compound n7 to compound n8 by the deprotection reaction of the formula (1). The deprotection reaction in this process can be carried out by a method commonly used for deprotecting an amino-protecting group.

[0363] (Method O) Among the raw material compounds (6), Q ３ is expressed by the following formula:

[0364]

[0365] Compound o4, which is any group selected from the following, can be produced according to the following method.

[0366]

[0367] [In the formula, A １ , A ２ , and A ３ are each independently a carbon atom or a nitrogen atom, ｏ is a halogen atom, a pinacolatoboryl group, or the like; Y １ is a nitro group or a halogen atom, R ｏ１ is R ８ , or R ６’ and R ｏ４ is R ８ , or R ６’ and A １ is a nitrogen atom, R ｏ２ does not exist, A １ is a carbon atom, R ｏ２ is a hydrogen atom or a halogen atom, or ｏ１ and R ｏ２ are bonded to each other to form the following formula:

[0368]

[0369] (wherein the lower end of the partial structure is R ｏ２ and the upper end of the partial structure is R ｏ１ A may form any partial structure selected from the group represented by ２ is a nitrogen atom, R ｏ３ does not exist, A ２ is a carbon atom, R ｏ３ is a hydrogen atom or a halogen atom, ３ is a nitrogen atom, R ｏ４ does not exist, A ３ is a carbon atom, R ｏ４ is a hydrogen atom or a halogen atom.

[0370] Compound o1 and compound o2 are known, or can be produced by appropriately combining known methods or methods similar thereto using known compounds as starting materials. Examples of the 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 is a step of nitrating or halogenating compound o1 to obtain compound o2. 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 acid solvent such as trifluoroacetic acid. The halogenation reaction in this step can be carried out under the same conditions as in the first step of Method N.

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

[0373] (Method P) Among the raw material compounds (6), Q ３ is expressed by the following formula:

[0374]

[0375] Compound p5, which is any group selected from the following, can be produced according to the following method.

[0376]

[0377] [In the formula, A １ is CH or a nitrogen atom, ２ is CH ２ or NH, ｐ is a halogen atom, Rｐ１ , R ｐ２ , and R ｐ３ are each independently 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 ester under heating in a solvent such as dichloroethane in the presence of an acid such as boronic acid or paratoluenesulfonic acid.

[0379] The second step is a step of obtaining compound p4 by urea formation from compound p2 and compound p3. The urea formation reaction in this step can be carried out under the same conditions as in the fourth step of Method L.

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

[0381] Next, equation (7):

[0382]

[0383] [In the formula, R ｘ’ is the following formula:

[0384]

[0385] The method for producing a starting compound represented by the formula (I) is shown below.

[0386] (Method Q) Among the raw material compounds (7), R ４ C optionally substituted with 1 to 3 halogen atoms １－６ C optionally substituted with an alkyl group or one trifluoromethyl group ３－６ Compound q12, which is a cycloalkylmethyl group, R ４ C optionally substituted with 1 to 3 halogen atoms １－６ Compound q11, which is an alkylcarbonyl group, and R ４Compound q14, in which R is a 6-membered heteroaryl group having one or two nitrogen atoms as ring atoms (the heteroaryl group may be substituted with one halogen atom), can be produced according to the following method. Although general production methods for each reaction site are shown in order, the respective steps do not necessarily have to be carried out in the order shown below as long as they do not affect the reaction substrates and reaction products.

[0387]

[0388] [In the formula, Pg １ is a protecting group for a carboxy group, M is a metal or a metal halide (e.g., magnesium halide, lithium halide, zinc halide, etc.), R ｑ１ is a hydrogen atom, C optionally substituted with 1 to 3 halogen atoms １－５ C optionally substituted with an alkyl group or one trifluoromethyl group ３－６ is a cycloalkyl group, R ｑ２ is the following formula:

[0389]

[0390] R is a group represented by ｑ３ is a 6-membered heteroaryl group having one or two nitrogen atoms as ring atoms (the heteroaryl group may be substituted with one halogen atom).

[0391] The first step is a step of obtaining compound q3 by aldol condensation reaction of compound q1 with compound q2. The aldol condensation reaction in this step can be carried out by reacting compound q1 with compound q2 using, for example, acetic acid and piperidine as catalysts.

[0392] The second step is a step of 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 with compound q4 in a solvent such as THF in the presence of a copper reagent such as copper(II) bromide. The reaction temperature is preferably from -78°C to room temperature.

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

[0394] The fourth step is a step of reducing the cyano group of compound q6 to obtain compound q7. 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 under heating in a solvent such as THF.

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

[0396] In the sixth step, compound q9 is condensed with compound q10 to give compound q11. The condensation reaction in this step can be carried out under the same conditions as in the first step of Method J.

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

[0398] The eighth step is a step of obtaining compound q14 from compound q9 and compound q13 by Buchwald amination or aromatic nucleophilic substitution. The Buchwald amination in this step can be carried out, for example, 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 in this step can be carried out, for example, 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] (Method R) Among the compounds represented by formula (7), L １ Compound r4, in which is —C(═O)—, can be prepared according to the following method.

[0400]

[0401] wherein R is a group represented by the following formula:

[0402]

[0403] and M is a dihydroxyboryl group, a pinacolatoboryl group, or the like.

[0404] The first step is a step of converting carboxylic acid r1 to 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 is a coupling reaction between compound r2 and compound r3 to obtain compound r4. The coupling reaction in this step can be carried out, for example, by reacting compound r2 with compound r3 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(0). An example of a literature description of this step is Catalysts 2019, 9(1), 53.

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

[0407]

[0408] [In the formula, Pg ３ is a protecting group for a hydroxy group (e.g., a methyl group, a benzyl group, a methoxymethyl group, etc.), Lg is a leaving group, R ａ is the following formula:

[0409]

[0410] or a group that can be converted into a group represented by the formula, ｂ is 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, ｃ is C optionally substituted with 1 to 3 halogen atoms １－６ is an alkyl group.

[0411] The first step is to form a protecting group Pg ３ The deprotection reaction in this step can be carried out by a method commonly used for deprotecting a hydroxyl group. For example, Pg ３ When s1 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 a step of triflating the hydroxy group of compound s2 to obtain compound s3. The triflating 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 in the presence of a base such as pyridine.

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

[0414] The fourth step is a step of obtaining compound s7 from compound s2 by alkylation 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 alkyl halide in a solvent such as DMF in the presence of a base such as potassium carbonate under heating. The reaction temperature is preferably from room temperature to 150°C.

[0415] Next, equation (8):

[0416]

[0417] [In the formula, R ｙ’ is the following formula:

[0418]

[0419] is a group that can be converted into a group represented by the following formula (1):

[0420] Among the raw material compounds (8), the compound of the following formula:

[0421]

[0422] As expressed by ４ However, compounds in which the formula is —C(═O)— can be prepared by a method similar to that of Method H.

[0423] Among the raw material compounds (8), the compound of the following formula:

[0424]

[0425] As expressed by ４ But CH ２ The compound represented by the formula: can be prepared by a method similar to Method I.

[0426] (Method T) Among the raw material compounds (8), L ４ Compound t6, wherein L is NH; ４ But N-R ９ (R ９ is C １－６ Compound t8, which is an alkyl group, can be prepared according to the following method.

[0427]

[0428] [In the formula, X ｔ is a halogen atom, and Pg ２ is a protecting group for an amino group.

[0429] The first step is a step of obtaining compound t2 from compound t1 by reduction 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 on carbon in a solvent such as ethanol or THF under a hydrogen atmosphere.

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

[0431] The third step is to convert the amino group of compound t4 into a protecting group Pg ２ The deprotection reaction in this step can be carried out by a method commonly used for deprotecting an amino group. For example, Pg ２ When is a tert-butoxycarbonyl group, the reaction 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 a reductive amination reaction to obtain compound t6 from compound t2 and compound t5. The reductive amination reaction in this step can be carried out under the same conditions as in the second step of Method I. Alternatively, the reductive amination reaction in this step can be carried out by reacting compound t2 and compound t5 with a reducing agent such as borane-THF complex in a solvent such as THF.

[0433] The fifth step is a step of obtaining compound t8 from compound t6 and compound t7 by 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]

[0436] The method for producing the starting compound represented by the formula:

[0437] (Method U) Among the raw material compounds (9), L １ Compound u3, L １ Compound u6, in which Q is a single bond; １ However, compounds u12 and u13, which are 7-azaspiro[3.5]nonane rings, can be prepared according to the following methods.

[0438]

[0439] [In the formula, R ｕ１ａ , R ｕ１ｂ , R ｕ１ｃ , and R ｕ１ｄ are each independently a hydrogen atom, a halogen atom, or C １－６ is an alkyl group, R ｕ２ is a hydroxy group or a leaving group, where R ｕ２ is a hydroxy group, R ｕ３ is a hydroxy group or a leaving group, or R ｕ２ is a leaving group, R ｕ３ is a hydroxy group), Y １ is a halogen atom, a trifluoromethanesulfonyloxy group, a pinacolatoboryl group, or a dihydroxyboryl group, １ is a halogen atom or a trifluoromethanesulfonyloxy group, ２ is a pinacolatoboryl group or a dihydroxyboryl group, or Y １ is a pinacolatoboryl group or a dihydroxyboryl group, Y ２ is a halogen atom or a trifluoromethanesulfonyloxy group), Rｘ’ is the following formula:

[0440]

[0441] and Pg １ is a protecting group for a carboxy group.

[0442] The first step is a step of obtaining compound u3 from compound u1 and compound u2. ｕ２ is a hydroxy group, and R ｕ３ When R is a hydroxy 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 azodicarboxylate such as diisopropyl azodicarboxylate in a solvent such as tetrahydrofuran. ｕ２ , or R ｕ３ When 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 under heating in a solvent such as DMF or DMA.

[0443] The second step is a step of obtaining 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 in the presence of 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 a step of obtaining compounds u9 and u10 from compounds u7 and u8 by 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 is a step of reducing compound u9 to give compound u11. The reduction reaction in this step can be carried out under the same conditions as in the first step of Method M.

[0446] The fifth step is a step of obtaining compound u12 by oxidation 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-benziodoxol-3-(1H)-one or manganese(IV) oxide in a solvent such as dichloromethane.

[0447] Compound u13 can also be obtained by subjecting compound u10 to the same steps as in the fourth and fifth steps of this method.

[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 with a molecule (e.g., DAX1 peptide) known to specifically bind to SF-1 (particularly the SF-1 ligand binding domain (LBD)), and SF-1 (particularly the SF-1-LBD), and quantifying the reduction in the binding rate to SF-1 by the molecule known to specifically bind to SF-1 (e.g., IC 50 Generally, in such test systems, the IC 50 A test substance with an IC value of 100 μM or less is considered to specifically bind to SF-1. Thus, in one aspect of the present invention, a compound or multifunctional molecule according to the present invention has an IC value of 100 μM or less with respect to reducing the rate of binding to SF-1 by a molecule known to specifically bind to SF-1 (e.g., DAX1 peptide). 50 value, preferably 10 μM or less 50 particularly preferably has an IC value of 1 μM or less 50In another aspect of the present invention, the compound or polyfunctional molecule according to the present invention has an IC value of 100 μM or less with respect to reducing the binding rate of the DAX1 peptide to SF-1-LBD in the test system and under the test conditions disclosed in Test Example 1 of the present specification. 50 value, preferably 10 μM or less 50 particularly preferably has an IC value of 1 μM or less 50 It has a value.

[0449] In one embodiment 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 the cells for a certain period of time, and then quantifying the decrease in the expression level of SF-1 target genes (e.g., CYP11A1, CYP17A1, CYP21A2, STAR, etc.) (e.g., IC 50 Generally, in such a test system, the IC value of SF-1 against the target gene can be measured. 50 A test substance with an IC value of 100 μM or less is considered to have antagonist activity against SF-1. Thus, in one aspect of the present invention, a compound or multifunctional molecule according to the present invention has an IC value of 100 μM or less against a target gene of SF-1 (e.g., CYP11A1, CYP17A1, CYP21A2 and / or STAR). 50 value, preferably 10 μM or less 50 particularly preferably has an IC value of 1 μM or less 50 In another aspect of the present invention, the compound or polyfunctional molecule according to the present invention has an IC value of 100 μM or less against CYP11A1, CYP17A1, CYP21A2 and / or STAR in the test system and under the test conditions disclosed in Test Example 2 of the present specification. 50 value, preferably 10 μM or less 50 particularly preferably has an IC value of 1 μM or less 50 It has a value.

[0450] In one embodiment 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 a 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) at the endogenous SF-1 gene locus in SF-1-expressing cells, adding a 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, the concentration that induces 50% degradation of SF-1 (DC 50 A test substance having a DC value of 100 μM or less is considered to have SF-1 degradation-inducing activity. Therefore, in one aspect of the present invention, the compound or polyfunctional molecule according to the present invention has a DC value of 100 μM or less against SF-1. 50 value, preferably a DC of 10 μM or less 50 particularly preferably a DC value of 1 μM or less 50 In another aspect of the present invention, the compound or polyfunctional molecule according to the present invention has a DC value of 100 μM or less against SF-1 in the test system and under the test conditions disclosed in Test Example 3 of the present specification. 50 value, preferably a DC of 10 μM or less 50 particularly preferably a DC value 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 of tumors. In another embodiment of the present invention, the compound or polyfunctional molecule according to the present invention has growth inhibitory activity against adrenocortical carcinoma. 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, an adrenocortical carcinoma cell line. The growth inhibitory activity against tumor cells can be measured using any known method, and typically can be measured by adding a 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, the concentration that inhibits tumor cell growth by 50% (GI 50 A test substance having a GI of 100 μM or less is considered to have growth inhibitory activity. Thus, in one embodiment of the present invention, the compound or multifunctional molecule according to the present invention has a GI of 100 μM or less against tumor cells (e.g., NCI-H295R cells). 50 value, preferably a GI of 10 μM or less 50 particularly preferably a GI of 1 μM or less 50 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 under the test conditions disclosed in Test Example 4 of the present specification. 50 value, preferably a GI of 10 μM or less 50 particularly preferably a GI of 1 μM or less 50 It has a value.

[0452] In one embodiment of the present invention, the compounds or multifunctional molecules of the present invention have antitumor activity against tumor cells in which SF-1 is involved in the development and progression of tumors, such as NCI-H295R cells, an adrenocortical carcinoma cell line, VCaP cells, or tumors derived from prostate cancer patients, in animal models (e.g., mice) subcutaneously transplanted. Antitumor activity in transplant models can be measured using any known method, for example, using protocols such as those described in Test Examples 5 and 6 of the present specification. Furthermore, the therapeutic effect of the compounds or multifunctional molecules of the present invention on breast cancer can be measured using, for example, a protocol such as that described in Test Example 7 of the present specification.

[0453] The present invention will be explained in detail by the following examples, but these are merely examples and do not limit the present invention, and may be changed within the scope of the present invention. In the following examples, "%" indicates mol / mol% for yield, vol% for solvents used in chromatography, and wt% for other matters. Nuclear magnetic resonance spectroscopy (hereinafter 1For H-NMR (resonance frequency 400 MHz or 500 MHz), chemical shift values ​​are reported as δ values ​​(ppm) using tetramethylsilane as the standard substance or the chemical shift value of the deuterated solvent used as the reference value. 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: deuterated 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) methanesulfonate methanesulfonate (S)-(-)-Tol-BINAP: (S)-(-)-2,2'-bis(di-p-tolylphosphino)-1,1'-binaphthyl XantPhos: 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (CAS registration number: 161265-03-8) IPA: isopropyl alcohol DCM: dichloromethane DMSO: dimethyl sulfoxide TLC: thin layer chromatography

[0454] In the following examples, compounds of the formula:

[0455]

[0456] The structure represented by the following formula indicates that the asymmetric carbon in the structure is a mixture of α- and β-configuration.

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

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

[0459] <Example A2> Ethyl [4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl](cyano)acetate The title compound was obtained in the same manner as in <Example C3> using the compound obtained in <Example A1> and 4-chlorophenylmagnesium bromide (CAS registration number: 873-77-8).

[0460] <Example A3> 2-[4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine The title compound was obtained by using the compound obtained in <Example A2> and performing the same operations as in <Example C4> and <Example C5> in this order.

[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) was added 1,1'-(azodicarbonyl)dipiperidine (24.8 g, 98.3 mmol) portionwise at room temperature, followed by stirring 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 successively with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The precipitated solid was filtered off and washed with a mixed solvent of hexane / ethyl acetate (1 / 1). The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (5.94 g, 21.5 mmol, yield 26%).

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

[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 Using the compound obtained in <Example A5>, the title compound was obtained by carrying out the same operations as in <Example D2> and <Example S4> in this order.

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

[0465] <Example B2> 2-{2,2-dimethyl-4-[4-(trifluoromethoxy)phenyl]tetrahydro-2H-pyran-4-yl}ethanamine The title compound was obtained by using the compound obtained in <Example B1> and performing the same operations as in <Example C4> and <Example C5> in this order.

[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 title compound was obtained in the same manner as in <Example D1> using the compounds obtained in <Example A4> and <Example B2>.

[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 title compound was obtained in the same manner as in <Example D2> using the compound obtained in <Example B3>.

[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 The title compound was obtained in the same manner as in <Example S4> using the compound obtained in <Example B4>.

[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) was added sulfuric acid (0.086 mL, 1.60 mmol), and the mixture was heated to reflux for 7 hours. The reaction mixture was returned to room temperature and concentrated under reduced pressure. The residue was diluted with ethyl acetate and washed successively with saturated aqueous sodium bicarbonate and saturated brine. The organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure to obtain the title compound (2.66 g, 14.3 mmol, 89% yield).

[0470] Example C2 Ethyl [trans-4-(2-chloro-4-formylphenoxy)cyclohexyl]acetate The title compound was obtained in the same manner as in Example A4 using the compound obtained in Example C1 and 3-chloro-4-hydroxybenzaldehyde (CAS registration number: 2420-16-8).

[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) bromide dimethyl sulfide complex (0.805 g, 3.92 mmol) was added at -78°C and 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 at the same temperature over 20 minutes. The reaction mixture was stirred for 1.5 hours while warming to room temperature, and then left at room temperature overnight. Copper(I) bromide dimethyl sulfide complex (0.805 g, 3.92 mmol) was added to the reaction mixture at -78 °C and stirred at the same temperature for 5 minutes. 4-Methoxyphenylmagnesium bromide (0.50 mol / L THF solution, 47 mL, 23.5 mmol) was then added dropwise over 5 minutes at the same temperature, and the mixture was stirred for 6 hours while warming 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 give the title compound (6.72 g, 20.3 mmol, 51% yield).

[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) was added sodium hydroxide (3.26 g, 81.5 mmol) at room temperature, and the mixture was stirred at 150°C for 7 hours and then left at room temperature overnight. To the reaction mixture, ice, water, and 1 mol / L hydrochloric acid were added under ice cooling, and the pH was adjusted to 1-2. The mixture was then extracted with DCM. The resulting organic layer was washed successively 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 give the title compound (5.91 g, 22.8 mmol, 70% yield).

[0473] Example C5 2-[4-(4-Methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine 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 warming to room temperature, 4 hours at 35° C., and 2 hours at 50° C. After cooling, water (3.2 mL) was added to the reaction solution under ice cooling, followed by addition of a 1 mol / L aqueous sodium hydroxide solution (3.2 mL) and water (9.0 mL). The resulting 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 title 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 title compound was obtained in the same manner as in Example D1 using the compounds obtained in Example C2 and Example C5.

[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 The title compound was obtained in the same manner as in <Example D2> using the compound obtained in <Example C6>.

[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 title compound was obtained in the same manner 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 Ethyl trans-4-(4-formylphenoxy)cyclohexanecarboxylate (4.00 g, 14.5 mmol) was added to a solution of 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine (3.89 g, 14.8 mmol) in toluene (72.4 mL) at room temperature, and the mixture was heated to reflux under a Dean-Stark apparatus. The mixture was stirred for 7 hours while the solvent was gradually removed, and then allowed to stand at room temperature overnight. The reaction mixture was heated to reflux under a Dean-Stark apparatus. The mixture was stirred for 1 hour while the solvent was gradually removed, and then allowed to cool, and the organic solvent was evaporated under reduced pressure. The resulting residue was dissolved in methanol (145 mL), and sodium borohydride (0.714 g, 17.4 mmol) was added under ice cooling. The mixture was stirred at the same temperature for 5 minutes and then warmed to room temperature for 1.5 hours. Saturated aqueous ammonium chloride and water were added to the reaction mixture under ice cooling, and the mixture was left overnight. The reaction mixture was extracted with DCM, and the resulting organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (DCM / methanol) to give the title compound (5.13 g, 9.79 mmol, 68% yield).

[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) were added triethylamine (0.588 mL, 4.24 mmol) and pivaloyl chloride (421 mg, 3.49 mmol) under ice cooling, and the mixture was stirred at room temperature for 2.5 hours. Water was added to the reaction solution under ice cooling, and the mixture was extracted with DCM. The resulting organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (1.19 g, 1.96 mmol, yield 92%).

[0479] Example D3 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-{[(2,2-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) was added 1 mol / L aqueous sodium hydroxide solution (9.71 mL, 9.71 mmol) at room temperature, followed by stirring at the same temperature for 30 minutes and allowing to stand overnight. The reaction solution was neutralized with the addition of 1 mol / L hydrochloric acid (9.71 mL, 9.71 mmol) under ice-cooling, and the organic solvent was then evaporated under reduced pressure. The resulting 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 give the title 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 Racemic ethyl trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylate was subjected to optical resolution by chiral HPLC [column: CHIRALPAK IC (registered trademark, Daicel Corporation), mobile phase: hexane / ethanol=50 / 50 (V / V)] to obtain the title compound 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 The title compound was obtained in the same manner as in <Example S4> using the compound obtained in <Example E1>.

[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) was added sodium thiomethoxide (0.484 g, 6.90 mmol) at room temperature, followed by stirring at 100°C for 8 hours and then allowing to stand at room temperature overnight. A saturated aqueous ammonium chloride solution and water were added to the reaction solution at room temperature, followed by extraction with ethyl acetate and DCM. The resulting organic layer was dried over anhydrous sodium sulfate and then filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (DCM / methanol) to obtain the title 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 DIPEA (2.05 mL, 11.8 mmol) and iodoethane (0.940 mL, 11.8 mmol) were added 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) at room temperature, followed by stirring at room temperature for 1 hour and then standing at room temperature overnight. DIPEA (0.819 mL, 4.70 mmol) and iodoethane (0.376 mL, 4.70 mmol) were added to the reaction mixture at room temperature, and the mixture was stirred at the same temperature for 10 hours and then allowed to stand at room temperature for 2 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 successively 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 give the title 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 Potassium carbonate (146 mg, 1.06 mmol) and 2-bromopropane (0.0991 mL, 1.06 mmol) were added 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) at room temperature, followed by stirring at 130° C. for 4.5 hours and then standing at room temperature for 4 days. Water was added to the reaction mixture at room temperature, followed by extraction 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 give the title 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 Using the compound obtained in <Example F3>, the title compound was obtained in the same manner as in <Example S4>.

[0486] Example G1 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 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) was added pyridine (1.32 mL, 16.3 mmol) under ice cooling, and then trifluoromethanesulfonic anhydride (0.333 mL, 1.98 mmol) was added portionwise, and the mixture was stirred at the same temperature for 30 minutes and then 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 washed successively 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 give the title compound (915 mg, 1.26 mmol, yield 96%).

[0487] Example G2 Ethyl trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(pyrrolidin-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 (50.0 mg, 0.0689 mmol) in 1,4-dioxane (1.38 mL) was added at room temperature to a solution of tris(dibenzylideneacetone)dipalladium(0) (6.3 mg, 0.0069 mmol), 2-(di-tert-butylphosphino)biphenyl (4.1 mg, To the mixture were added 1,2-dimethyl-2,4-trimethyl-1,2-trimethyl ...

[0488] <Example G3> trans-4-(4-{[(2,2-dimethylpropanoyl)(2-{2,2-dimethyl-4-[4-(pyrrolidin-1-yl)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example G2>, the title compound was obtained in a manner similar to that 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 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 registration number: 25952-53-8) (56 mg, 0.29 mmol), and 4-dimethylaminopyridine (54 mg, 0.44 mmol) were dissolved in DCM (2 To a solution of 1 mL of methylcellulose, N,N-dimethylsulfamide (CAS reg. no.: 3984-14-3) (36 mg, 0.29 mmol) was added at room temperature, and the mixture was stirred at room temperature for 1 day. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with ethyl acetate and washed successively with 1 mol / L hydrochloric acid, water, and saturated brine. The organic layer was dried over anhydrous sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (DCM / methanol) to give the title 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}(pyridin-2-yl)amino]methyl}phenoxy)cyclohexanecarboxylate 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) was added with 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). The reaction mixture was stirred at 100°C for 2 hours. Potassium phosphate 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, followed by stirring at 100°C for 8 hours. RuPhos Pd G3 (4 mg, 0.005 mmol) was then added to the reaction mixture, followed by stirring 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, followed by stirring at 100°C for 4 hours. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The resulting organic layers were combined, 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 title 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}(pyridin-2-yl)amino]methyl}phenoxy)cyclohexanecarboxylic acid The title compound was obtained in the same manner as in <Example S4> using the compound obtained in <Example I1>.

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

[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]ethanamine (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 thereto, and the mixture was stirred at room temperature for 20 hours. Water and saturated aqueous sodium bicarbonate were added to the reaction mixture, followed by extraction with DCM. The organic layer was dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate / methanol) to give the title 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), HATU (205 mg, 0.538 mmol) and DIPEA (0.187 mL, 1.08 mmol) were added, and the mixture was stirred under a nitrogen atmosphere at room temperature for 3 days. Water was added to the reaction mixture, which was 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 give the title 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 Using the compound obtained in <Example J3>, the title compound was obtained in the same manner as in <Example S4>.

[0496] Example K1: Benzyl (cis-4-hydroxycyclohexyl)acetate. To a solution of 4-hydroxyphenylacetic acid (CAS Registry Number: 156-38-7) (10.0 g, 65.7 mmol) in ethanol (200 mL), rhodium-alumina (10.0 g) was added and the mixture was stirred at 50°C under a hydrogen atmosphere for 8 hours. The insoluble matter was filtered off through Celite and washed with ethanol. The resulting solution was concentrated to approximately 200 mL, and rhodium-alumina (10.0 g) was added. The mixture was stirred at 50°C under a hydrogen atmosphere for 4 hours. The 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 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 at room temperature overnight. The reaction mixture was diluted with diethyl ether, washed successively with water, 1 mol / L hydrochloric acid, and saturated brine, 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 give the title compound (7.65 g, 30.8 mmol, yield 47%).

[0497] Example K2 Benzyl [trans-4-(4-formylphenoxy)cyclohexyl]acetate The title compound was obtained in the same manner as in Example A4 using the compound obtained in Example K1 and 4-hydroxybenzaldehyde (CAS Registry Number: 123-08-0).

[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 title compound was obtained in the same manner as in Example D1 using the compounds obtained in Example K2 and Example C5.

[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 Using the compound obtained in Example K3 and 3,3,3-trifluoropropionaldehyde (CAS Registry Number: 460-40-2), the title compound was obtained 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 Using the compound obtained in <Example K4>, the title compound was obtained in the same manner 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 title compound was obtained in the same manner as in Example G2 using the compound obtained in Example G1 and methylamine (2.0 mol / L THF solution).

[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 Using the compound obtained in <Example L1>, the title compound was obtained in the same manner as in <Example S4>.

[0503] Example M1: 2-[(4R)-4-(4-Methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine Racemic 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine was subjected to optical resolution by chiral HPLC [column: CHIRALCEL OZ-H (registered trademark, Daicel Corporation), mobile phase: hexane / IPA = 60 / 40 (V / V)] to obtain the title compound as the component eluted later. Analysis 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 minutes, S-isomer 6.7 minutes

[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 registration number: 889940-13-0) (18.0 g, 115 mmol) in DMF (150 mL) was added to HATU (43.8 g, 115 mmol), and the mixture was stirred at room temperature for 20 minutes. The reaction mixture was cooled to 0°C and stirred for 5 minutes. A solution of 2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine (25.2 g, 95.7 mmol) in DMF (150 mL) and DIPEA (50 mL, 287 mmol) were added dropwise to the reaction mixture, followed by stirring at room temperature for 24 hours. The reaction mixture was diluted with ethyl acetate, washed sequentially with aqueous sodium bicarbonate, water, and saturated brine, 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 give the title 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-dimethylpropan-1-amine. To a solution of 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) in THF (60 mL) was added borane-THF complex (0.89 mol / L THF solution, 240 mL, 210 mmol) and stirred under reflux for 9 hours. After cooling to room temperature, methanol (60 mL) was added and the mixture was stirred under reflux for 3 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was added with ethyl acetate, washed successively with water and saturated brine, 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) and dried under reduced pressure to give the title 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 title compound was obtained in the same manner as in Example T1 using the compounds obtained in Example M3 and Example A4.

[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 title compound was obtained in a manner similar to that in <Example S4> using the compound obtained in <Example M4>.

[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 title compound was obtained by using the compound obtained in <Example C5> and 4-(4-bromophenoxy)benzaldehyde (Bioorg. Med. Chem. Lett., 2004, 14, 4179-4183.) and performing the same operations as in <Example D1> and <Example D2> in this order.

[0509] Example N2: N-{4-[(4-{[dimethyl(oxide)-λ 6N-[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) was added 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). (S)-(-)-Tol-BINAP (27 mg, 0.040 mmol) and palladium(II) acetate (8 mg, 0.04 mmol) were added to the reaction mixture, and the mixture was stirred under reflux under a nitrogen atmosphere for 9 hours. To the reaction mixture, 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, and the mixture was stirred under reflux under a nitrogen atmosphere for 8 hours. To the reaction mixture, (S)-(-)-Tol-BINAP (27 mg, 0.040 mmol) and palladium(II) acetate (8 mg, 0.04 mmol) were further added, and the mixture was stirred under reflux under a nitrogen atmosphere for 4 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM / methanol) to give the title compound (7 mg, 0.01 mmol, 4% yield).

[0510] Example O1 Ethyl trans-4-(4-{[(5-fluoropyrimidin-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 registration 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 2-chloro-5-fluoropyrimidine (CAS registration number: 62802-42-0) (0.030 mL, 0.24 mmol) were added. To the reaction mixture were added cesium fluoride (1 mg, 0.007 mmol), and the mixture was stirred at 150°C for 1.5 hours under microwave irradiation. Water and saturated brine were added to the reaction mixture, followed by extraction with ethyl acetate. The resulting organic layers were combined, 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 give the title compound (47.4 mg, 0.0765 mmol, yield 61%).

[0511] <Example O2> trans-4-(4-{[(5-fluoropyrimidin-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 title compound was obtained in a manner similar to that in <Example S4>.

[0512] Example P1: Methyl 2-[4-(4-formylphenoxy)phenyl]propanoate 4-Fluorobenzaldehyde (CAS Registry Number: 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, then returned to room temperature and left overnight. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title 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 title compound was obtained in the same manner as in Example T1 using Example M3 and the compound obtained in Example P1.

[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 title compound was obtained in the same manner 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 title compound was obtained in the same manner as in Example J2 using the compound obtained in Example C5 and methyl 4-formyl-2-methylbenzoate (CAS Registry Number: 74733-23-6).

[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 registration 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 thereto, 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 aqueous sodium bicarbonate were added to the reaction mixture, and the mixture was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title 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 Using the compound obtained in <Example Q2>, the title compound was obtained 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 to the mixture, which was stirred at room temperature for 1.5 hours. The solvent was then evaporated to give the corresponding acid chloride (1.06 g, 1.87 mmol, 97% yield). To the resulting 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. The reaction mixture was cooled 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, and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate). The resulting crude product was dissolved in ethanol (4.0 mL), and 1 mol / L aqueous sodium hydroxide solution (0.754 mL, 0.754 mmol) was added. 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 and 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 give the title compound (15.0 mg, 0.0220 mmol, 15% yield).

[0519] Example R1 Ethyl (2S)-2-ethoxy-3-[4-(4-formylphenoxy)phenyl]propanoate Using 4-fluorobenzaldehyde (CAS Registry Number: 459-57-4) and ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate (CAS Registry Number: 222555-06-8), the title compound was obtained in the same manner 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 title compound was obtained in the same manner as in Example T1 using the compound obtained in Example M3 and Example R1.

[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 Using the compound obtained in <Example R2>, the title compound was obtained in a manner similar to that 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 to a solution of ethyl 2-(4-oxocyclohexyl)acetate (CAS Registry Number: 58012-34-3) (7.75 g, 42.1 mmol) in THF (170 mL) at −78° C. After the dropwise addition, the mixture was stirred at −78° C. for 2 hours. A saturated aqueous solution of ammonium chloride and water were added to the reaction solution, and the mixture was returned to room temperature. The THF was distilled off under reduced pressure, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, 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 title compound (6.13 g, 32.9 mmol, yield 78%).

[0523] Example S2 Ethyl {trans-4-[(5-formylpyridin-2-yl)oxy]cyclohexyl}acetate The title compound was obtained in the same manner as in Example A4 using the compound obtained in Example S1 and 6-hydroxynicotinaldehyde (CAS registration number: 106984-91-2).

[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}pyridin-2-yl)oxy]cyclohexyl}acetate The title compound was obtained in the same manner as in Example T1 using the compounds obtained in Example S2 and Example M3.

[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}pyridin-2-yl)oxy]cyclohexyl}acetate 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}pyridin-2-yl)oxy]cyclohexyl}acetate (390 mg, 0.588 mmol) in methanol (11.8 mL) was added to a solution of 1 mol / L sodium hydroxide aqueous solution (2.94 mL, 2.94 mmol) at room temperature. After stirring at 50°C for 30 minutes, the mixture was left standing at room temperature overnight. 1 mol / L hydrochloric acid (2.94 mL, 2.94 mmol) was added to the reaction mixture at room temperature, followed by extraction with DCM. 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 (hexane / ethyl acetate) to give the title compound (265 mg, 0.418 mmol, 71% yield).

[0526] Example T1 Benzyl [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]acetate Benzyl [trans-4-(4-formylphenoxy)cyclohexyl]acetate (450 mg, 1.28 mmol) and acetic acid (0.199 mL, 3.48 mmol) were added to a solution of 3,3,3-trifluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropan-1-amine (450 mg, 1.16 mmol) in methanol (11.6 mL) at room temperature, and the mixture was stirred at 50°C for 1 hour. After cooling, sodium cyanoborohydride (137 mg, 2.18 mmol) was added to the reaction mixture under ice cooling, and the mixture was stirred at room temperature for 3 hours and then allowed to stand for 2 days. The reaction mixture was stirred at 50°C for 1.5 hours. After cooling, ice, water, and sodium bicarbonate were added to the reaction mixture under ice cooling, and the mixture was extracted with DCM. The resulting organic layer was washed with saturated brine, 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 title compound (569 mg, 0.785 mmol, yield 68%).

[0527] <Example T2> [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 Using the compound obtained in <Example T1>, the title compound was obtained in the same manner as in <Example S4>.

[0528] Example U1 N-[4-(benzyloxy)benzyl]-2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine The title compound was obtained in the same manner as in Example D1 using the compound obtained in Example M1 and 4-benzyloxybenzaldehyde (CAS Registry Number: 4397-53-9).

[0529] Example U2 N-[4-(benzyloxy)benzyl]-3,3-difluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide The title compound was obtained in the same manner as in Example Q2 using the compound obtained in Example U1 and 3,3-difluoro-2,2-dimethylpropanoic acid (CAS registration number: 1022154-50-2).

[0530] Example U3: 3,3-difluoro-N-(4-hydroxybenzyl)-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide N-[4-(benzyloxy)benzyl]-3,3-difluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide (920 mg, 1.59 mmol) in ethanol (30 mL) was added 10% palladium carbon (400 mg), and the mixture was stirred under a hydrogen atmosphere at room temperature for 4 hours. The reaction mixture was diluted with ethyl acetate, and the insoluble matter was filtered off through Celite. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (DCM / methanol) to obtain the title compound (714 mg, 1.46 mmol, yield 92%).

[0531] Example U4 (cis-4-{[tert-butyl(diphenyl)silyl]oxy}cyclohexyl)methyl 4-methylbenzenesulfonate To a solution of (cis-4-{[tert-butyl(diphenyl)silyl]oxy}cyclohexyl)methanol (WO2007126041 A1) (8.20 g, 22.2 mmol) in DCM (200 mL) were added triethylamine (4.63 mL, 33.4 mmol) and p-toluenesulfonyl chloride (4.67 g, 24.5 mmol), and the mixture was stirred under reflux for 7 hours. After the reaction mixture was cooled to room temperature, ethanol (2 mL) was added, and the mixture was stirred at room temperature for 10 hours. Water and saturated brine were added, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (8.89 g, 17.0 mmol, yield 76%).

[0532] Example U5 tert-Butyl({cis-4-[(methylsulfanyl)methyl]cyclohexyl}oxy)diphenylsilane Sodium thiomethoxide (9.54 g, 136 mmol) was added to a solution of (cis-4-{[tert-butyl(diphenyl)silyl]oxy}cyclohexyl)methyl 4-methylbenzenesulfonate (8.89 g, 17.0 mmol) in THF (400 mL), and the mixture was stirred under reflux for 10 hours. The reaction mixture was cooled to room temperature, and water and saturated brine were added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine, 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 title compound (6.28 g, 15.8 mmol, yield 93%).

[0533] Example U6 tert-Butyl({cis-4-[(methylsulfinyl)methyl]cyclohexyl}oxy)diphenylsilane Sodium periodate (4.04 g, 18.9 mmol) was added to a solution of tert-butyl({cis-4-[(methylsulfanyl)methyl]cyclohexyl}oxy)diphenylsilane (6.28 g, 15.8 mmol) in methanol (100 mL) and water (25 mL), and the mixture was stirred at room temperature for 15 hours. Saturated brine and water were added to the reaction solution, and the mixture was extracted with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (DCM / methanol) to obtain the title compound (6.41 g, 15.5 mmol, yield 98%).

[0534] Example U7: Benzyl {[(cis-4-{[tert-butyl(diphenyl)silyl]oxy}cyclohexyl)methyl](methyl)oxide-λ 6 To a solution of tert-butyl({cis-4-[(methylsulfinyl)methyl]cyclohexyl}oxy)diphenylsilane (6.41 g, 15.5 mmol) and benzyl carbamate (CAS RN: 621-84-1) (7.01 g, 46.4 mmol) in DCM (250 mL) was added magnesium oxide (4.98 g, 124 mmol), iodobenzene diacetate (14.9 g, 46.4 mmol), and rhodium(II) acetate dimer (1.37 g, 3.09 mmol) under a nitrogen atmosphere. The mixture was heated under reflux and stirred for 7 hours. After filtering off insoluble material, the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (3.97 g, 7.04 mmol, 46% yield).

[0535] Example U8: Benzyl {[(cis-4-hydroxycyclohexyl)methyl](methyl)oxide-λ 6 -sulfanylidene}carbamate benzyl {[(cis-4-{[tert-butyl(diphenyl)silyl]oxy}cyclohexyl)methyl](methyl)oxide-λ6 To a solution of {-sulfanylidene}carbamate (3.97 g, 7.04 mmol) in THF (30 mL), tetrabutylammonium fluoride (1.0 mol / L THF solution, 30 mL, 30 mmol) was added and stirred at 65°C for 2 hours. The reaction mixture was cooled to room temperature, and water and saturated brine were added, followed by extraction with ethyl acetate. The combined organic layer was washed with saturated brine, 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 title compound (1.70 g, 5.22 mmol, 74% yield).

[0536] Example U9: Benzyl {(R) or (S)-[(cis-4-hydroxycyclohexyl)methyl](methyl)oxide-λ 6 -sulfanylidene}carbamate racemic benzyl {[(cis-4-hydroxycyclohexyl)methyl](methyl)oxide-λ 6 The {-sulfanylidene}carbamate was subjected to optical resolution by chiral HPLC [column: CHIRALPAK IC (registered trademark, Daicel Corporation), mobile phase: hexane / ethanol = 40 / 60 (V / V)] to obtain the title compound as the component eluting first.

[0537] Example U10: Benzyl [(R) or (S)-{[trans-4-(4-{[(3,3-difluoro-2,2-dimethylpropanoyl){2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexyl]methyl}(methyl)oxide-λ 6 -sulfanylidene]carbamate Using the compounds obtained in Example U9 and Example U3, the title compound was obtained in the same manner as in Example A4.

[0538] Example U11 3,3-Difluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethyl-N-{4-[(trans-4-{[(R) or (S)-S-methylsulfonimidoyl]methyl}cyclohexyl)oxy]benzyl}propanamide The title compound was obtained in the same manner as in Example U3 using the compound obtained in Example U10.

[0539] Example V1: tert-Butyl 2'-fluoro-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate 4-bromo-3-fluorobenzaldehyde (CAS registration number: 133059-43-5) (4.00 g, 19.7 mmol), tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-cyclohexene-1-carboxylate (CAS registration number: 1562375-30-7) (6.38 g, 20.7 mmol), [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride DCM adduct (0.804 g, 0.985 mmol), and sodium carbonate (6.27 g, 59.2 mmol) were dissolved in 1,4-dioxane (45 The residue was dissolved in a mixed solvent of 1 mL of hexane and water (5 mL) and stirred under nitrogen atmosphere at 85°C for 4 hours. After the reaction mixture was returned to room temperature, saturated aqueous sodium bicarbonate was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over 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 title compound (6.03 g, 19.8 mmol, yield: quantitative).

[0540] Example V2: tert-butyl (4R)-2'-fluoro-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate Example V3: tert-butyl (4S)-2'-fluoro-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate The racemic tert-butyl 2'-fluoro-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate was purified by chiral HPLC [column: CHIRALPAK IG (registered trademark, Daicel Corporation), mobile phase: acetonitrile] to give the R-form (Example V2) as the component that eluted first and the S-form (Example V3) as the component that eluted later. Analysis conditions: Column: CHIRALPAK IG (registered trademark, Daicel Corporation), size: 0.46 cm x 25 cm, flow rate: 1.0 mL / min, temperature: 40°C, mobile phase: acetonitrile, retention time: R-isomer (Example V2) 4.8 minutes, S-isomer (Example V3) 5.6 minutes

[0541] Example V4: (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-carboxylate tert-Butyl (4R)-2'-fluoro-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate (0.115 g, 0.378 mmol) and 3,3,3-trifluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropan-1-amine (0.147 g, 0.379 mmol) were dissolved in DCM (4 The resulting mixture was dissolved in 1 mL of HCl, and sodium triacetoxyborohydride (0.157 g, 0.741 mmol) was added, followed by stirring at room temperature for 20 hours. Saturated aqueous sodium bicarbonate was added to the reaction mixture, followed by extraction with DCM. The organic layer was dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (0.196 g, 0.290 mmol, 77% yield).

[0542] Example V5 (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 monohydrochloride (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 tert-butyl ester (0.196 g, 0.290 mmol) was dissolved in DCM (2 mL) and diluted with 4 mol / L hydrogen chloride / 1,4-dioxane solution (1.2 mL, The reaction mixture was concentrated under reduced pressure to give the title compound (0.237 g, 0.361 mmol, yield: quantitative).

[0543] Example W1 tert-Butyl 4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate tert-Butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-cyclohexene-1-carboxylate (CAS Registry Number: 1562375-30-7) (WO2017051355) (1.14 g, 3.70 mmol), 4-bromobenzaldehyde (CAS Registry Number: 1122-91-4) (694 mg, 3.75 mmol), [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium (II) DCM adduct (306 mg, 0.375 mmol), and potassium carbonate (2.0 mol / L aqueous solution, 3.5 mL, 7.0 A suspension of 1,4-dioxane (7.5 mL) of 1,4-dioxane (2.9 mmol) was stirred at 90°C for 2 hours under a nitrogen atmosphere. The reaction mixture was cooled to room temperature, and ethyl acetate and water were added. Insoluble matter was filtered off through Celite to separate the two layers. The organic layer was dried over sodium sulfate and then filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (836 mg, 2.92 mmol, 79% yield).

[0544] Example W2 tert-Butyl (4R)-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate Example W3 tert-Butyl (4S)-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate Racemic tert-butyl 4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate was purified by chiral SFC [column: CHIRALPAK IG (registered trademark, Daicel Corporation), mobile phase: sCO2 / acetonitrile=60 / 40 (V / V)] to give the R-isomer (Example W2) as the component eluting first and the S-isomer (Example W3) as the component eluting later. Analysis conditions Column: CHIRALPAK IG-3 (registered trademark, Daicel Corporation), size: 0.46 cm × 5 cm, flow rate: 3.0 mL / min, temperature: 35°C, mobile phase: sCO2 / acetonitrile (0.05% diethylamine) = 60 / 40 (V / V), retention time: R-isomer (Example W2) 0.9 min, S-isomer (Example W3) 1.4 min

[0545] Example W4 tert-Butyl (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-carboxylate A solution of 3,3,3-trifluoro-N-{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropan-1-amine (16.7 g, 43.1 mmol) and tert-butyl (4R)-4'-formyl-2,3,4,5-tetrahydro[biphenyl]-4-carboxylate (12.8 g, 44.7 mmol) in DCM ...

Claims

1. The following formula (1): [In the formula, A is -O-, -S-, -NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ is alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxyl, -CN, 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, wherein the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, an unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, -O-, -S-, -NH-, C １－３ Alkylene, C ２－３ alkenylene, -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; Ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur as ring members; R ５ is C １－６ Alkyl, carboxy, hydroxy, or the following formula: wherein C is a group represented by the formula: １－６ Alkyl is unsubstituted or includes carboxy, hydroxy and -O-C １－６ and n is an integer of 0 to 3, or a pharma- ceutically acceptable salt thereof.

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

3. n R's １ each independently represents a halogen, —O—C １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C １－３ Alkyl) ２ or a 3- to 7-membered heterocycloalkyl, wherein the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms, or a pharma- ceutically acceptable salt thereof.

4. R ２ and R ３ are each independently hydrogen or C １－６ 4. The compound according to claim 1, or a pharma- ceutically acceptable salt thereof, wherein R is an alkyl group.

5. R ４ But, C １－６ Alkyl, -C(=O)-R ｄ or 6- to 12-membered heteroaryl, wherein R ｄ is C １－６ alkyl, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens or C ３－７ 5. The compound according to claim 1, wherein said heteroaryl is substituted with cycloalkyl, and said heteroaryl has 1 or 2 nitrogen atoms as ring member atoms, or a pharma- ceutically acceptable salt thereof.

6. Ring Q １ But, C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, or C ３－７ 6. The compound according to claim 1, wherein the aromatic heterocycle is a cycloalkene ring and has one or two nitrogen atoms as ring member atoms, or a pharma- ceutically acceptable salt thereof.

7. L １ is a single bond, -O-, C １－３ The compound according to any one of claims 1 to 6, which is alkylene, or -C(=O)-, or a pharma- ceutically acceptable salt thereof.

8. Ring Q ２ But, C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ 8. The compound according to claim 1 , or a pharma- ceutically acceptable salt thereof, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring have one or two nitrogen atoms as ring member atoms.

9. The following formula (1'): [In the formula, A is -O- or -CF ２ - and R １ is a halogen, —O—C which may be substituted with 1 to 3 halogens １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C １－３ Alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member, R ２ and R ３ are each independently hydrogen or C １－６ is alkyl, R ４ C optionally substituted with 1 to 3 halogens １－６ Alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens １－６ C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring atoms (the heteroaryl may be substituted with 1 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; a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring atoms; ４－７ Cycloalkane ring, or C ４－７ is a cycloalkene ring; L １ is a single bond, -O-, -CH ２ - or -C(=O)-, and Ring Q ２ represents a benzene ring optionally substituted with one halogen atom; ４－７ Cycloalkane ring, C optionally substituted with one halogen ４－７ a cycloalkene ring, a piperidine ring, or a 7-azaspiro[3.5]nonane ring, and R ５ is carboxy, hydroxy and -O-C １－６ C which may have 1 or 2 groups selected from the group consisting of alkyl １－６ Alkyl, carboxy, hydroxy, or the following formula: or a pharma- ceutically acceptable salt thereof.

10. A is -O- and R ２ is methyl; R ３ is methyl; R ４ C optionally substituted with 1 to 3 halogens １－６ Alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens １－６ alkyl or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring atoms (the heteroaryl may be substituted with 1 halogen); Ring Q １ is halogen and C １－３ a benzene ring or a pyridine ring, each of which may have one group selected from the group consisting of alkyl; １ is a single bond, —O—, or —C(═O)—, and ring Q ２ is a benzene ring, C ４－７ Cycloalkane ring, or C ４－７ The compound according to claim 9 , or a pharma- ceutically acceptable salt thereof, wherein: R is a cycloalkene ring.

11. R １ is methoxy, and R ４ The compound according to claim 9 or 10, wherein is 3,3,3-trifluoro-2,2-dimethylpropyl, or a pharma- ceutically acceptable salt thereof.

12. 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}pyridin-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 or a pharma- ceutical acceptable salt thereof.

13. A polyfunctional molecule comprising a moiety corresponding to a compound according to any one of claims 1 to 12, or a pharma- ceutically acceptable salt thereof.

14. The compound or a pharma- ceutically acceptable salt thereof further comprises other functional moieties, and the moiety corresponds to R 5 The polyfunctional molecule of claim 13 , wherein the functional moiety is linked directly or via a linker at any point in the formula (I).

15. The multifunctional molecule of claim 14, wherein the other functional moiety 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.

16. The multifunctional molecule of claim 14, wherein the other functional moiety is an E3 ligase binding moiety.

17. The multifunctional molecule of claim 16, wherein the E3 ligase binding moiety is a cereblon (CRBN) binding moiety.

18. The following formula (2): [In the formula, A is -O-, -S-, -NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ is alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxyl, -CN, 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, wherein the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl, or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, an unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, -O-, -S-, -NH-, C １－３ Alkylene, C ２－３ alkenylene, -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; Ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen and sulfur as ring members; B is -L ２ -L ３ -L ４ -R ６ And L ２ is a single bond, C １－６ Alkylene, -C(=O)-, -C(=O)NH-, -(CH ２ ) ｋ -C(=O)NH- (k is an integer of 1 to 3), or -NHC(=O)-; L ３ is a single bond, C １－６ Alkylene, C ３－６ cycloalkylene, piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl; L ４ is a single bond, -NH-, -N(-R ７ ) - (R ７ is C １－６ alkyl), -CH ２ - or -C(=O)-, and R ６ 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; and n is an integer from 0 to 3, or a pharma- ceutically acceptable salt thereof.

19. A is -O- or -CR ｂ R ｃ The compound according to claim 18, wherein R is - or a pharma- ceutically acceptable salt thereof.

20. n R's １ each independently represents a halogen, —O—C １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C １－３ Alkyl) ２ or a 3- to 7-membered heterocycloalkyl, wherein said heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms, or a pharma- ceutically acceptable salt thereof.

21. R ２ and R ３ are each independently hydrogen or C １－６ 21. The compound of any one of claims 18 to 20, or a pharma- ceutically acceptable salt thereof, wherein: R is an alkyl group; 22. R ４ But, C １－６ Alkyl, -C(=O)-R ｄ or 6- to 12-membered heteroaryl, wherein R ｄ is C １－６ alkyl, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens or C ３－７ 22. The compound according to any one of claims 18 to 21, or a pharma- ceutically acceptable salt thereof, wherein said heteroaryl has one or two nitrogen atoms as ring member atoms.

23. Ring Q １ But, C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, or C ３－７ 23. The compound according to any one of claims 18 to 22, wherein the aromatic heterocycle is a cycloalkene ring and has 1 or 2 nitrogen atoms as ring member atoms, or a pharma- ceutically acceptable salt thereof.

24. L １ is a single bond, -O-, C １－３ The compound according to any one of claims 18 to 23, wherein the aryl group is alkylene, or -C(=O)-, or a pharma- ceutically acceptable salt thereof.

25. Ring Q ２ But, C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ 25. The compound according to any one of claims 18 to 24, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring have 1 or 2 nitrogen atoms as ring member atoms, or a pharma- ceutically acceptable salt thereof.

26. The following formula (2'): [In the formula, A is -O- or -CF ２ - and R １ is a halogen, —O—C which may be substituted with 1 to 3 halogens １－６ Alkyl, -N(H)-C １－３ Alkyl, -N(C １－３ Alkyl) ２ or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member, R ２ and R ３ are each independently hydrogen or C １－６ is alkyl, R ４ C optionally substituted with 1 to 3 halogens １－６ Alkyl, —C(═O)—C optionally substituted with 1 to 3 halogens １－６ C optionally substituted with one trifluoromethyl ３－６ cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring atoms (the heteroaryl may be substituted with 1 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; a 6- to 12-membered monocyclic or bicyclic aromatic heterocycle having one or two nitrogen atoms as ring atoms; ４－７ Cycloalkane ring, or C ４－７ is a cycloalkene ring; L １ is a single bond, -O-, -CH ２ - or -C(=O)-, and Ring Q ２ represents a benzene ring optionally substituted with one halogen atom; ４－７ Cycloalkane ring, C optionally substituted with one halogen ４－７ A 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 is a single bond, C １－６ Alkylene, -C(=O)-, -C(=O)NH-, -(CH ２ ) ｋ -C(=O)NH- (k is an integer of 1 to 3) or -NHC(=O)-, L ３ is a single bond, C １－６ Alkylene, C ３－６ cycloalkylene, piperazinediyl, piperazin-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediyl; L ４ is a single bond, -NH-, -N(-R ７ ) - (R ７ is C １－６ alkyl), -CH ２ - or -C(=O)-, and R ６ 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 pharma- ceutically acceptable salt thereof.

27. R ６ or a pharma- ceutically acceptable salt thereof.

28. The compound of claim 27, or a pharma- ceutically acceptable salt thereof, wherein the E3 ligase binding moiety is a cereblon (CRBN) binding moiety.

29. R ６ is expressed by the following formula: [In the above formula, R ８ is hydrogen or C １－６ alkyl; W, X, Y, and Z are each independently a nitrogen atom, a halogen atom, １－６ Alkyl and -O-C １－６ each of l, m, and n is an integer of 0 to 3; and the wavy line represents L. ４ 29. The compound according to claim 18, or a pharma- ceutically acceptable salt thereof, wherein the substituent is any one selected from the group consisting of:

30. R ６ is expressed by the following formula: [In the above formula, R ８ is hydrogen or C １－６ V is halogen, and the wavy line represents L ４ and wherein the substituent is any one of the substituents selected from the group consisting of:

31. R １ is —O—C, which may be substituted with 1 to 3 halogens; １－６ is alkyl, R ４ C optionally substituted with 1 to 3 halogens １－６ C optionally substituted with alkyl or one trifluoromethyl ３－６ cycloalkylmethyl, Ring Q １ is halogen and C １－６ a benzene ring which may have one or two groups selected from the group consisting of alkyl; a 9- to 10-membered bicyclic aromatic heterocycle having one or two nitrogen atoms as ring member atoms; ４－７ Cycloalkane ring, or C ４－７ is a cycloalkene ring, and L １ The compound according to any one of claims 18 to 30, or a pharma- ceutically acceptable salt thereof, wherein: is a single bond or -O-.

32. A is -O- and R ２ is methyl, and R ３ 32. The compound according to any one of claims 18 to 31, or a pharma- ceutically acceptable salt thereof, wherein: is methyl.

33. R １ is methoxy, and R ４ 33. The compound according to any one of claims 18 to 32, or a pharma- ceutically acceptable salt thereof, wherein: R is 3,3,3-trifluoro-2,2-dimethylpropyl.

34. Ring Q １ is a benzene ring optionally having one halogen atom, L １ is a single bond, and ring Q ２ is a cyclohexene ring, or a pharma- ceutically acceptable salt thereof.

35. 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-benzimidazol-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-benzimidazol-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-benzimidazol-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]quinolin-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]quinolin-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]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-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]quinoxalin-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 Any one of the compounds selected from (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 or a pharma- ceutical acceptable salt thereof.

36. (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]quinolin-1(2H)-yl]piperidine-2,6-dione monobenzenesulfonate.

37. (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]quinolin-1(2H)-yl]piperidine-2,6-dione monoethanesulfonate.

38. (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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione mono-10-camphorsulfonate.

39. (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]quinoxalin-1(2H)-yl]piperidine-2,6-dione monoethanesulfonate.

40. (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]quinoxalin-1(2H)-yl]piperidine-2,6-dione monosalicylate.

41. (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]quinoxalin-1(2H)-yl]piperidine-2,6-dione monobenzenesulfonate.

42. (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 mono-10-camphorsulfonate.

43. (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]quinolin-1(2H)-yl]piperidine-2,6-dione A crystal of benzenesulfonate salt, which has 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 radiation (λ=1.54 angstroms).

44. (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]quinolin-1(2H)-yl]piperidine-2,6-dione A crystal of ethanesulfonate salt, which has 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 radiation (λ=1.54 angstroms).

45. (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]piperidin-4-yl}amino)-2-oxo-5,6-dihydro-4H-imidazo[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione A crystal of 10-camphorsulfonate, which has 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 radiation (λ=1.54 angstroms).

46. ​​(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 A crystal of ethanesulfonate salt, which has 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 radiation (λ=1.54 angstroms).

47. (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 crystalline salicylate salt, which has 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 radiation (λ=1.54 angstroms).

48. (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 crystal of benzenesulfonate salt, which has 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 radiation (λ=1.54 angstroms).

49. (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 crystal of 10-camphorsulfonate, which has 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 a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms).

50. A composition for inhibiting Steroidogenic Factor 1, comprising a compound according to any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof, a polyfunctional molecule according to any one of claims 13 to 17, or a compound according to any one of claims 18 to 49 or a pharma- ceutically acceptable salt thereof, or a crystal thereof.

51. A composition for inducing the degradation of Steroidogenic Factor 1, comprising a polyfunctional molecule according to any one of claims 13 to 17, or a compound according to any one of claims 18 to 49, or a pharma- ceutically acceptable salt thereof, or a crystal thereof.

52. A pharmaceutical composition comprising a compound according to any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof, a polyfunctional molecule according to any one of claims 13 to 17, or a compound according to any one of claims 18 to 49 or a pharma- ceutically acceptable salt thereof, or a crystal thereof.

53. The pharmaceutical composition of claim 52 for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

54. A method for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism, comprising administering to a subject in need of such treatment an effective amount of a compound described in any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof, a polyfunctional molecule described in any one of claims 13 to 17, or a compound described in any one of claims 18 to 49 or a pharma-ceutically acceptable salt thereof, or a crystal thereof.

55. A compound according to any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof, a polyfunctional molecule according to any one of claims 13 to 17, or a compound according to any one of claims 18 to 49 or a pharma- ceutically acceptable salt thereof, or a crystal 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.

56. Use of a compound according to any one of claims 1 to 12 or a pharma- ceutically acceptable salt thereof, a polyfunctional molecule according to any one of claims 13 to 17, or a compound according to any one of claims 18 to 49 or a pharma-ceutically acceptable salt thereof, or a crystal thereof, in the manufacture of a medicament for the treatment of castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

57. The following formula (10): [In the formula, A is -O-, -S-, -NR ａ - or -CR ｂ R ｃ -, where R ａ is hydrogen or C １－３ is alkyl, R ｂ and R ｃ are each independently hydrogen, halogen, or C １－３ alkyl, and the alkyl is unsubstituted or substituted with 1 to 3 halogens, and n R １ are each independently a halogen, a hydroxyl, -CN, 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, wherein the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, and the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R ２ and R ３ are each independently hydrogen, halogen, or C １－６ Alkyl or C ２－６ alkenyl, wherein the alkyl and alkenyl are each independently 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, １－６ Alkyl is unsubstituted or contains 1 to 3 halogens, C ３－７ cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; Ring Q １ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ a cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with a halogen, an unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; L １ represents a single bond, -O-, -S-, -NH-, C １－３ Alkylene, C ２－３ alkenylene, -C(=O)-, -C(=O)NH-, -NHC(=O)-, -C(=O)O-, or -OC(=O)-, wherein the alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens; Ring Q ２ is C ６－１２ a monocyclic or bicyclic aromatic hydrocarbon ring of the formula: ３－７ Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C ３－７ Cycloalkene ring, 3- to 7-membered heterocycloalkene ring, C ５－１２ or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocycle, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with a halogen, unsubstituted C １－３ Alkyl and C １－３ haloalkyl; and the aromatic heterocycle, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring members; R １０ is C １－６ alkyl, wherein １－６ wherein alkyl is substituted with 1 to 2 3- to 7-membered heterocycloalkyl, the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, and the heterocycloalkyl is unsubstituted or substituted with an amino-protecting group, and n is an integer of 0 to 3, or a pharma- ceutically acceptable salt thereof.

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