3-Phenylpropylamine derivatives

Abstract

The present invention aims to provide a novel compound having SF-1 antagonist activity, a multifunctional molecule containing a moiety corresponding to the compound, particularly an SF-1 Degrader. The present invention relates to a 3-phenylpropylamine derivative compound represented by formula (1) etc., and a multifunctional molecule containing a moiety corresponding to the compound represented by formula (1) etc. JPEG0007688242000190.jpg40145

Description

Technical Field

[0001] The present invention relates to a novel compound having SF-1 antagonist activity, a multifunctional molecule containing a moiety corresponding to the compound, particularly an SF-1 degradation inducer, and a pharmaceutical composition containing the same.

Background Art

[0002] Steroidogenic factor 1 (also referred to as "SF1" or "SF-1") is a nuclear receptor expressed in the adrenal cortex, gonads, hypothalamus, and pituitary gland, and is an important molecule for the development of the adrenal gland and gonads (Non-Patent Document 1). The occurrence of adrenal tumors in mice overexpressing SF-1 (Non-Patent Document 2) and the reported example of overexpression of SF-1 protein in adrenal cortical cancer tissue (Non-Patent Document 3) suggest that SF-1 contributes to the occurrence and progression of adrenal tumors. On the other hand, it has been shown that SF-1 controls the expression of steroid hormone synthases such as CYP11A1 and CYP17A1 in the adrenal cortex and testis, and induces the production of steroid hormones such as androgen (Non-Patent Documents 4 and 5). Androgen is important for the occurrence and growth of prostate cancer. Although the progression is suppressed by hormonal therapy such as castration in the early stage of treatment, it progresses to castration-resistant prostate cancer that shows resistance to hormonal therapy. The growth of castration-resistant prostate cancer is known to depend on androgens derived from the adrenal gland (Non-Patent Document 6).

[0003] On the other hand, in recent years, the usefulness of a heterobifunctional molecule in which a moiety that binds to a target protein and a moiety that recruits an endogenous effector molecule are linked via a linker has been reported. By physically bringing the target protein and the endogenous effector molecule into close proximity, the heterobifunctional molecule causes a change in the target protein and exhibits the desired effect (Non-Patent Document 7).

[0004] As one of the technologies utilizing such hetero-bifunctional molecules, Targeted Protein Degradation (TPD) is known. TPD is a technology that induces the degradation of target proteins. By using a hetero-bifunctional molecule in which a binder moiety that binds to the target protein and a binder moiety that binds to the E3 ligase are linked by a linker, it induces the formation of a complex of the target protein and the E3 ligase in cells, and shows strong biological activity by inducing ubiquitination and degradation of the target protein. Although more than 600 types of E3 ligases have been identified, those used in TPD are limited. In particular, Cereblon (CRBN) and Von Hippel-Lindau (VHL) can be mentioned (Non-Patent Document 8). Especially, the binder moiety that binds to CRBN (also called "CRBN ligand") is widely used in TPD, and its various structures and usefulness have been reported (Patent Documents 1-9, Non-Patent Document 9). Although various proteins have been reported as the targets in TPD, a target protein degradation inducer targeting SF-1 has not been reported so far.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Patent Document 8

[0006] [Non-Patent Document 1] Parker KL, Schimmer BP, Steroidogenic factor 1: a key determinant of endocrine development and function. Endocr Rev., 1997; 18: 361-77. [Non-Patent Document 2] Doghman M, Karpova T, Rodrigues GA, et al., Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endocrinol., 2007; 21: 2968-87. [Non-Patent Document 3] Sbiera S, Schmull S, Assie G, et al., High Diagnostic and Prognostic Value of Steroidogenic Factor-1 Expression in Adrenal Tumors. J Clin Endocrinol Metab., 2010; 95: E161-71. [Non-Patent Document 4] 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. [Non-Patent Document 5] Lin L, Achermann J, C: Steroidogenic Factor-1 (SF-1, Ad4BP, NR5A1) and Disorders of Testis Development. Sex Dev., 2008; 2: 200-209.

Non-Patent Document 6

Non-Patent Document 7

Non-Patent Document 8

Non-Patent Document 9

Summary of the Invention

Problems to be Solved by the Invention

[0007] An object of the present invention is to provide a novel compound having SF-1 antagonist activity, a multifunctional molecule containing a moiety corresponding to the compound, particularly an SF-1 degrader. A further object of the present invention is to provide a composition for inhibiting SF-1 containing the compound or multifunctional molecule, a composition for inducing the degradation of SF-1, or a pharmaceutical composition. Another object of the present invention is to provide a method for treating a disease (particularly, cancer such as castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, etc., Cushing's syndrome, or primary aldosteronism), which includes administering the compound or multifunctional molecule. Yet another object of the present invention is to provide an intermediate that can be used in the production of the compound or multifunctional molecule.

Means for Solving the Problems

[0008] As a result of intensive studies, the present inventors have found that a 3-phenylpropylamine derivative compound represented by the following formula (1) etc. has SF-1 antagonist activity, and also found that a multifunctional molecule containing a moiety corresponding to the compound represented by the formula (1) etc. can degrade SF-1 protein and can inhibit the growth of tumor cells, thereby completing the present invention. That is, the present invention relates to the following. [1] The following formula (1):

[0009]

Chemical formula

[0010] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -, and here, R a is hydrogen or C 1-3 alkyl, and R band R c is, independently of one another, hydrogen, halogen, or C 1-3 alkyl, and said alkyl is unsubstituted or substituted with 1 to 3 halogens, n R's 1 are, independently of one another, halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, wherein said alkyl and alkenyl are, independently of one another, unsubstituted or substituted with 1 to 3 halogens, said cycloalkyl and heterocycloalkyl are, independently of one another, unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3 are, independently of one another, hydrogen, halogen, C 1-6 alkyl, or C 2-6 alkenyl, wherein said alkyl and alkenyl are, independently of one another, unsubstituted or substituted with 1 to 3 halogens, R 4 is C 1-6 alkyl, -C(=O)-R d (R d is C 1-6 alkyl, C 2-5 alkenyl, C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl), C 6-12Aryl, or a 6- to 12-membered heteroaryl, wherein, said C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens, C 3-7 cycloalkyl, or a 3- to 7-membered heterocycloalkyl, said aryl, heteroaryl, cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, C 3-7 cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, wherein, said aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said aromatic heterocyclic ring, heterocycloalkane ring, and heterocycloalkene ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, L 1 is 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 a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a monocyclic or bicyclic aromatic heterocyclic ring of 6 to 12 members, a C 3-7 cycloalkane ring, a heterocycloalkane ring of 3 to 7 members, a C 3-7 cycloalkene ring, a heterocycloalkene ring of 3 to 7 members, a C 5-12 spirocycloalkane ring, or a spiroheterocycloalkane ring of 5 to 12 members, wherein the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 5 is C 1-6 alkyl, carboxy, hydroxy, or a group represented by the following formula:

[0011]

Chemical formula

[0012] and wherein the C 1-6 alkyl is unsubstituted or substituted with 1 to 2 groups selected from the group consisting of carboxy, hydroxy, and -O-C 1-6 alkyl, and n is an integer from 0 to 3], or a pharmaceutically acceptable salt thereof. [2] A is -O- or -CR b R c -, the compound according to [1] or a pharmaceutically acceptable salt thereof. [3] n R's 1 are each independently halogen, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , or 3- to 7-membered heterocycloalkyl, wherein the heterocycloalkyl has 1 or 2 nitrogen atoms as ring member atoms, the compound according to [1] or [2] or a pharmaceutically acceptable salt thereof. [4] R 2 and R 3 are each independently hydrogen or C 1-6 alkyl, the compound according to any one of [1] to [3] or a pharmaceutically acceptable salt thereof. [5] R 4 is C 1-6 alkyl, -C(=O)-R d , or 6- to 12-membered heteroaryl, wherein the R d is C 1-6 alkyl, the C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens or C 3-7 cycloalkyl, and the heteroaryl has 1 or 2 nitrogen atoms as ring member atoms, the compound according to any one of [1] to [4] or a pharmaceutically acceptable salt thereof. [6] Ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a monocyclic or bicyclic aromatic heterocyclic ring of 6 to 12 members, a C 3-7 cycloalkane ring, or a C 3-7The 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 pharma- ceutically acceptable salt thereof. [7] L 1 is a single bond, -O-, C 1-3 The compound according to any one of [1] to [6], which is alkylene, or -C(=O)-, or a pharma- ceutically acceptable salt thereof. [8] Ring Q 2 But, C 6-12 monocyclic or bicyclic aromatic hydrocarbon rings of C 3-7 Cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C 3-7 A cycloalkene ring, or a 5- to 12-membered spiroheterocycloalkane ring, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring have 1 or 2 nitrogen atoms as ring member atoms. The compound according to any one of [1] to [7], or a pharma- ceutical acceptable salt thereof. [9] The following formula (1'):

[0013] [ka]

[0014] [In the formula, A is -O- or -CF 2 - and R 1 is a halogen, -OC 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 halogens1-6 alkyl, -C(=O)-C optionally substituted with 1 to 3 halogens 1-6 alkyl, C optionally substituted with 1 trifluoromethyl 3-6 cycloalkylmethyl, or 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring members (the heteroaryl may be optionally substituted with 1 halogen), ring Q 1 is a benzene ring optionally having 1 or 2 groups selected from the group consisting of halogen and C 1-3 alkyl, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having 1 or 2 nitrogen atoms as ring members, C 4-7 cycloalkane ring, or C 4-7 cycloalkene ring, L 1 is a single bond, -O-, -CH 2 -, or -C(=O)-, ring Q 2 is a benzene ring optionally substituted with 1 halogen, C 4-7 cycloalkane ring, C optionally substituted with 1 halogen 4-7 cycloalkene ring, piperidine ring, or 7-azaspiro[3.5]nonane ring, and R 5 is C optionally having 1 or 2 groups selected from the group consisting of carboxy, hydroxy and -O-C 1-6 alkyl, carboxy, hydroxy, or a group represented by the following formula: 1-6 alkyl, carboxy, hydroxy, or a compound represented by:] or a pharmaceutically acceptable salt thereof.

[0015]

Chemical formula

[0016]

[10] A is -O-, R 2 is methyl, R 3 is methyl, R​4 is C which may be substituted with 1 to 3 halogens 1-6 alkyl, -C(=O)-C 1-6 alkyl which may be substituted with 1 to 3 halogens, or 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 a benzene ring which may have 1 group selected from the group consisting of halogen and C 1-3 alkyl, or a pyridine ring, L 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 cycloalkene ring, The compound according to [9] or a pharmaceutically acceptable salt thereof.

[11] R 1 is methoxy, and R 4 is 3,3,3-trifluoro-2,2-dimethylpropyl, The compound according to [9] or

[10] 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 any one compound selected therefrom 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] Further comprising other functional moieties, wherein the moiety corresponding to the compound or a pharmaceutically acceptable salt thereof is R 5The multifunctional molecule described in

[13] , which is directly connected to other functional parts or connected via a linker at any position.

[15] The multifunctional molecule described in

[14] , wherein the other functional part is an E3 ligase binding part, 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 described in

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

[17] The multifunctional molecule described in

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

[18] The following formula (2):

[0017]

Chemical formula

[0018] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c - and Here, R a is hydrogen or C 1-3 alkyl, and 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 halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3Alkyl, -N(C 1-3 alkyl) 2 、C 3-7 cycloalkyl, or a 3- to 7-membered heterocycloalkyl, where herein, the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3 are each independently hydrogen, halogen, C 1-6 alkyl, or C 2-6 alkenyl, where herein, 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 a 3- to 7-membered heterocycloalkyl), C 6-12 aryl, or a 6- to 12-membered heteroaryl, where herein, the C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens, C 3-7 cycloalkyl, or a 3- to 7-membered heterocycloalkyl, and the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with halogen, unsubstituted C 1-3 alkyl and C 1-3substituted with 1 to 3 groups selected from the group consisting of haloalkyl, and said heteroaryl and heterocycloalkyl each have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, a C 3-7 cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, a C 3-7 cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, wherein, said aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said aromatic heterocyclic ring, heterocycloalkane ring, and heterocycloalkene ring each have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, L 1 is 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, said alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens, ring Q 2 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, a C 3-7 cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, a C 3-7 cycloalkene ring, a 3- to 7-membered heterocycloalkene ring, a C 5-12a spirocycloalkane ring or a 5- to 12-membered spiroheterocycloalkane ring, and wherein the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring and spiroheterocycloalkane ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, B is -L 2 -L 3 -L 4 -R 6 wherein L 2 is a single bond, C 1-6 alkylene, -C(=O)-, -C(=O)NH-, -(CH 2 ) k -C(=O)NH- (k represents an integer from 1 to 3), or -NHC(=O)-, L 3 is a single bond, C 1-6 alkylene, C 3-6 cycloalkylene, piperazinediyl, piperazine-2-onediyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediy, L 4 is a single bond, -NH-, -N(-R 7 )- (R 7 represents C 1-6 alkyl), -CH 2 -, or -C(=O)-, and R 6is 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, a compound represented by n being an integer from 0 to 3 or a pharmaceutically acceptable salt thereof.

[19] A is -O- or -CR b R c -, the compound according to

[18] or a pharmaceutically acceptable salt thereof.

[20] n R's 1 are each independently halogen, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , or 3- to 7-membered heterocycloalkyl, where the heterocycloalkyl has 1 or 2 nitrogen atoms as ring members, the compound according to

[18] or

[19] or a pharmaceutically acceptable salt thereof.

[21] R 2 and R 3 are each independently hydrogen or C 1-6 alkyl, the compound according to any one of

[18] to

[20] or a pharmaceutically acceptable salt thereof.

[22] R 4 is C 1-6 alkyl, -C(=O)-R d , or 6- to 12-membered heteroaryl, where the R d is C 1-6 alkyl, the C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens or C 3-7 cycloalkyl, and The heteroaryl is a compound described in any one of

[18] to

[21] having 1 or 2 nitrogen atoms as ring member atoms or a pharmaceutically acceptable salt thereof.

[23] Ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a monocyclic or bicyclic aromatic heterocyclic ring of 6 to 12 members, a C 3-7 cycloalkane ring, or a C 3-7 cycloalkene ring, wherein the aromatic heterocyclic ring has 1 or 2 nitrogen atoms as ring member atoms, a compound described in any one of

[18] to

[22] or a pharmaceutically acceptable salt thereof.

[24] L 1 is a single bond, -O-, C 1-3 alkylene, or -C(=O)-, a compound described in any one of

[18] to

[23] or a pharmaceutically acceptable salt thereof.

[25] Ring Q 2 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a C 3-7 cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, a C 3-7 cycloalkene ring, or a 5- to 12-membered spiroheterocycloalkane ring, wherein the heterocycloalkane ring and the spiroheterocycloalkane ring have 1 or 2 nitrogen atoms as ring member atoms, a compound described in any one of

[18] to

[24] or a pharmaceutically acceptable salt thereof.

[26] The following formula (2’):

[0019]

Chemical formula

[0020] [wherein, A is -O- or -CF 2 -, and R 1 is halogen, -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, -N(H)-C 1-3Alkyl, -N(C 1-3 alkyl) 2 , or a 4- to 6-membered heterocycloalkyl having one nitrogen atom as a ring member atom, R 2 and R 3 are each independently hydrogen or C 1-6 alkyl, R 4 is C 1-6 alkyl which may be substituted with 1 to 3 halogens, -C(=O)-C 1-6 alkyl which may be substituted with 1 to 3 halogens, C 3-6 cycloalkylmethyl which may be substituted with one trifluoromethyl, or 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), Ring Q 1 is a benzene ring which may have 1 or 2 groups selected from the group consisting of halogen and C 1-3 alkyl, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having 1 or 2 nitrogen atoms as ring member atoms, C 4-7 cycloalkane ring, or C 4-7 cycloalkene ring, L 1 is a single bond, -O-, -CH 2 -, or -C(=O)-, Ring Q 2 is a benzene ring which may be substituted with one halogen, C 4-7 cycloalkane ring, C 4-7 cycloalkene ring which may be substituted with one halogen, piperidine ring, or 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- (where k represents an integer from 1 to 3), or -NHC(=O)-, L 3 is a single bond, C 1-6 alkylene, C 3-6 cycloalkylene, piperazinediyl, piperazine - 2 - one diyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3 - oxa - 9 - azabicyclo[3.3.1]nonane diyl, L 4 is a single bond, -NH-, -N(-R 7 )-(R 7 represents 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] a compound represented by or a pharmaceutically acceptable salt thereof.

[27] R 6 is an E3 ligase binding moiety, the compound according to any one of

[18] to

[26] or a pharmaceutically acceptable salt thereof.

[28] The E3 ligase binding moiety is a cereblon (CRBN) binding moiety, the compound according to

[27] or a pharmaceutically acceptable salt thereof.

[29] R 6 is the following formula:

[0021]

Chemical formula

[0022] [In the above formula, R 8 is hydrogen, or C 1-6 alkyl, W, X, Y, and Z are each independently a nitrogen atom, or a halogen, C 1-6Alkyl and -O-C 1-6 a carbon atom which may have one group selected from the group consisting of alkyl, l, m, and n each independently represent an integer from 0 to 3, and the wavy line represents any group selected from the bonds with L 4 a compound according to any one of

[18] to

[28] or a pharmaceutically acceptable salt thereof, which is any group selected from the bonds with L

[30] R 6 is the following formula:

[0023]

Chemical formula

[0024] [wherein, R 8 is hydrogen or C 1-6 alkyl, V is halogen, and the wavy line represents any group selected from the bonds with L 4 a compound according to

[29] or a pharmaceutically acceptable salt thereof, which is any group selected from the bonds with L

[31] R 1 is -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, R 4 is C 1-6 alkyl which may be substituted with 1 to 3 halogens, or C 3-6 cycloalkylmethyl which may be substituted with one trifluoromethyl group, ring Q 1 is a benzene ring which may have one or two groups selected from the group consisting of halogen and C 1-6 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 cycloalkene ring, and L 1 is a single bond or -O-, The compound according to any one of

[18] to

[30] or a pharmaceutically acceptable salt thereof.

[32] A is -O-, R 2 is methyl, and R 3 is methyl, The compound according to any one of

[18] to

[31] or a pharmaceutically acceptable salt thereof.

[33] R 1 is methoxy, and R 4 is 3,3,3-trifluoro-2,2-dimethylpropyl, The compound according to any one of

[18] to

[32] or a pharmaceutically acceptable salt thereof.

[34] Ring Q 1 is a benzene ring which may have one halogen, L 1 is a single bond, and Ring Q 2 is a cyclohexene ring, The compound according to any one of

[18] to

[33] or a pharmaceutically acceptable salt thereof.

[35] 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]quinoxalin-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]quinoxalin-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]quinoxalin-1(2H)-yl}piperidine-2,6-dione any one compound selected therefrom or a pharmaceutically acceptable salt thereof. [35-2] 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, 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]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]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]quinoxalin-1(2H)-yl]piperidine-2,6-dione Any one compound selected therefrom 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 mono-benzenesulfonate. [36-3] (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxane-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazin-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] A crystal of 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, 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 rays (λ = 1.54 Å). [36-6] The crystal of (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, 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å).

[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]quinolin-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]quinolin-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] A crystal of 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 ethanesulfonate, 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å). [37-6] The crystal of (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, 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα line (λ = 1.54 Å).

[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]quinolin-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]quinolin-1(2H)-yl}piperidine-2,6-dione monohydrate 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 monohydrate 10-camphorsulfonate. [38-5] A crystal of 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 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 rays (λ = 1.54 Å). [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 10-camphorsulfonate crystal, 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å).

[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]quinoxalin-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]quinoxalin-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] A crystal of 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]quinoxalin-1(2H)-yl}piperidine-2,6-dione ethanesulfonate, 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 rays (λ = 1.54 Å). [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]quinoxalin-1(2H)-yl]piperidine-2,6-dione ethanesulfonate, which is a crystal of ethanesulfonate and 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ = 1.54 Å).

[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]quinoxalin-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]quinoxalin-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] A crystal of 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]quinoxalin-1(2H)-yl}piperidine-2,6-dione salicylate, 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 rays (λ = 1.54 Å). [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]quinoxalin-1(2H)-yl]piperidine-2,6-dione salicylate crystals, 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 rays (λ = 1.54 Å).

[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]quinoxalin-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]quinoxalin-1(2H)-yl}piperidine-2,6-dione mono-benzenesulfonate. [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 mono-benzenesulfonate. [41-5] Crystals of 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]quinoxalin-1(2H)-yl}piperidine-2,6-dione benzenesulfonate, which 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 in a powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ = 1.54 Å). [41-6] The crystal of (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, 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å).

[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]quinoxalin-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]quinoxalin-1(2H)-yl}piperidine-2,6-dione mono-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. [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]quinoxalin-1(2H)-yl]piperidine-2,6-dione monohydrate 10-camphorsulfonate. [42-5] Crystals of 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]quinoxalin-1(2H)-yl}piperidine-2,6-dione 10-camphorsulfonate, which 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 in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ = 1.54 Å). [42-6] The crystal of (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxetan-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, 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 the powder X-ray diffraction pattern obtained by irradiation with copper Kα line (λ = 1.54 Å).

[43] A composition for inhibiting Steroidogenic Factor 1, containing 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 crystals thereof.

[44] A composition for inducing the degradation of Steroidogenic Factor 1, containing 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 crystals thereof.

[45] A pharmaceutical composition, containing 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 crystals thereof.

[46] The pharmaceutical composition according to

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

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

[47] A method for treating castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism, which comprises administering to a subject in need of treatment for castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism, an effective amount of 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] , or a compound or a pharmaceutically acceptable salt thereof according to any one of

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

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

[48] For use in the treatment of castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism, 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. [48-2] For use in the treatment of castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism, 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.

[49] Use of 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, in the manufacture of a medicament for the treatment of castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism. [49-2] Use of 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, in the manufacture of a medicament for the treatment of castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

[50] The following formula (10):

[0025]

Chemical formula

[0026] [wherein, A is -O-, -S-, -NR a -, or -CR b R c -, and here, R a is hydrogen or C 1-3 alkyl, and 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, n R 1 are each independently halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, here, the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3 are each independently hydrogen, halogen, C 1-6 alkyl, or C 2-6 alkenyl, here, 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, the C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens, C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C 3-7 cycloalkene ring, or 3- to 7-membered heterocycloalkene ring, wherein, the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and The aromatic heterocyclic ring, heterocycloalkane ring, and heterocycloalkene ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, L 1 is 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 one to three halogens, ring Q 2 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a monocyclic or bicyclic aromatic heterocyclic ring of 6 to 12 members, C 3-7 cycloalkane ring, a heterocycloalkane ring of 3 to 7 members, C 3-7 cycloalkene ring, a heterocycloalkene ring of 3 to 7 members, C 5-12 spirocycloalkane ring of, or a spiroheterocycloalkane ring of 5 to 12 members, wherein, the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with one to three groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have one or two heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 10 is C 1-6 alkyl, wherein, the C 1-6 alkyl is substituted with one to two 3- to 7-membered heterocycloalkyls, 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 a protecting group for an amino group, and n is an integer from 0 to 3], a compound represented thereby or a pharmaceutically acceptable salt thereof. For example, when the item numbers are indicated in a range as in the above “

[18] to [42-6]”, if there are items including branch numbers such as [36-3] and [42-4] within the range, the items including the branch numbers are also included in the range.

Advantages of the Invention

[0027] 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 used as an SF-1 antagonist or an SF-1 inhibitor. Further, since SF-1 is known to be involved in the occurrence and progression of various diseases such as adrenocortical cancer 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. Further, 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 used as a partial structure in a larger molecule (for example, a polyfunctional molecule) by combining it with other functional moieties. In addition, since the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof specifically binds to SF-1, it can also be used as an SF-1 binder. Further, by combining a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof with other functional portions, it can also be used as an SF-1 binding moiety in a larger molecule (for example, a polyfunctional molecule). Among them, a polyfunctional molecule containing a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof and an E3 ligase binding portion, particularly, the compound represented by formula (2) of the present invention or a pharmaceutically acceptable salt thereof, or a crystal thereof, can degrade the SF-1 protein and inhibit the growth of tumor cells, and thus can be used as an SF-1 inhibitor and an SF-1 degrader, and can also be used for the treatment of SF-1 related diseases such as adrenocortical cancer and castration-resistant prostate cancer.

Brief Description of Drawings

[0028]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Mode for Carrying Out the Invention

[0029] <1. Definition> Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. In case of conflict between the meaning defined in this specification and the commonly understood meaning by one of ordinary skill in the art for a certain term, the meaning defined in this specification shall prevail. Preferred methods and materials are described below, but methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All references (including patent documents and non-patent documents) cited in this specification are hereby incorporated by reference in their entirety. The materials, methods, and examples disclosed in this specification are illustrative only and not intended to be limiting.

[0030] In this specification, Steroidogenic factor 1 means the protein encoded by the NR5A1 gene, and may be denoted by the abbreviations or synonyms SF-1, hSF-1, SF1, Ad4BP, AD4BP, ELP, FTZ1, TZF1, POF7, SPGF8, SRXX4, or SRXY3.

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

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

[0033] As used herein, "alkyl" means a linear or branched alkyl. As used herein, "C 1-6 alkyl" means an alkyl having 1 to 6 carbon atoms, and "C 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 a linear or branched alkylene. As used herein, "C 1-6 alkylene" means an alkylene having 1 to 6 carbon atoms, and "C 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" means a linear or branched alkenyl. As used herein, "C 2-6 alkenyl" means an alkenyl having 2 to 6 carbon atoms, and "C 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" means a linear or branched alkenylene. As used herein, "C2-3 "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, etc.

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

[0038] In this specification, "aromatic hydrocarbon ring" means a monocyclic or polycyclic hydrocarbon ring in which at least one of the rings is an aromatic ring. In this specification, "aryl" means a group derived from an aromatic hydrocarbon ring. "C 6-12 aryl" means an aryl containing 6 to 12 carbon atoms as ring member atoms, and "C 6-12 monocyclic or bicyclic aromatic hydrocarbon ring of" 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, "aromatic heterocyclic ring" means a monocyclic or polycyclic ring in which at least one of the rings is an aromatic ring and contains, as ring member atoms, one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur. As used herein, "heteroaryl" means a group derived from an aromatic heterocyclic ring. "6- to 12-membered heteroaryl" means a heteroaryl consisting of 6 to 12 ring member atoms, and "6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring" means a monocyclic or bicyclic aromatic heterocyclic ring consisting of 6 to 12 ring member atoms. Examples of the "aromatic heterocyclic ring" include, but are not limited to, thiophene, pyrrole, pyrazole, triazole, oxazole, oxadiazole, thiazole, pyridine, pyrimidine, pyridazine, pyrazine, quinoline, quinoxaline, benzothiophene, benzimidazole, benzotriazole, benzofuran, etc. Examples of the "heteroaryl" include, but are not limited to, thienyl, pyrrolyl, pyrazolyl, triazolyl, oxazolyl, oxadiazolyl, thiazolyl, pyridyl, pyrimidyl, pyridazyl, pyrazinyl, quinolyl, quinoxalyl, benzothiophenyl, benzimidazolyl, benzotriazolyl, benzofuranyl, etc.

[0040] As used herein, examples of the "6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms" include pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, etc.

[0041] As used herein, examples of the "6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having 1 or 2 nitrogen atoms as ring member atoms" include pyridine, pyrazine, pyrimidine, Six-membered rings such as pyridazine; seven-membered rings such as azepine, 1,2-diazepine, 1,3-diazepine, 1,4-diazepine; eight-membered rings such as azocine; nine-membered rings such as azonine; six / five-membered fused rings such as indole, isoindole, indazole, benzimidazole, imidazopyridine (including imidazo[1,2-a]pyridine); and six / six-membered fused rings such as quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline can be mentioned, but are not limited thereto. In the present specification, examples of the "nine- to ten-membered bicyclic aromatic heterocyclic ring having one or two nitrogen atoms as ring member atoms" include, but are not limited to, six / five-membered fused rings such as indole, isoindole, indazole, benzimidazole, imidazopyridine (including imidazo[1,2-a]pyridine); and six / six-membered fused rings such as quinoline, isoquinoline, quinazoline, quinoxaline, cinnoline.

[0042] In the present specification, the "cycloalkane ring" means a hydrocarbon ring that does not contain an unsaturated bond. In the present specification, the "cycloalkyl" means a monovalent group derived from a cycloalkane ring. The "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. In the present specification, "C 3-7 cycloalkane ring" and "C 4-7 cycloalkane ring" each mean a cycloalkane ring having 3 to 7 and 4 to 7 carbon atoms, respectively, and "C 3-7 cycloalkyl" and "C 3-6 cycloalkyl" each mean a cycloalkyl having 3 to 7 and 3 to 6 carbon atoms, respectively, and "C 5-12 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" means a divalent group derived from a cycloalkane ring. As used herein, "C 3-6 cycloalkylene" means a cycloalkylene having 3 to 6 carbon atoms. Examples of "cycloalkylene" include, but are not limited to, cyclobutylene, cyclopentylene, cyclohexylene, etc.

[0044] As used herein, "cycloalkene ring" means a hydrocarbon ring containing at least one carbon-carbon double bond. As used herein, "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. As used herein, "C 3-7 cycloalkene ring" means a cycloalkene ring having 3 to 7 carbon atoms, and "C 4-7 cycloalkene ring" means a cycloalkene ring having 4 to 7 carbon atoms. Examples of "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, cycloheptatriene, etc.

[0045] As used herein, "heterocycloalkane ring" means a saturated ring containing, as ring atoms, one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur. As used herein, "heterocycloalkyl" means a monovalent group derived from a heterocycloalkane ring. The "heterocycloalkane ring" may be a monocyclic heterocycloalkane, a fused bicyclic heterocycloalkane, a spiro ring, or a bridged heterocycloalkane in which two non-adjacent atoms of the ring are linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms. As used herein, "3- to 7-membered heterocycloalkane ring" means a heterocycloalkane ring having a total of 3 to 7 carbon atoms and heteroatoms as ring atoms, "5- to 12-membered spiroheterocycloalkane ring" means a spiroheterocycloalkane ring having a total of 5 to 12 carbon atoms and heteroatoms as ring atoms, and "3- to 7-membered heterocycloalkyl" means a heterocycloalkyl having a total of 3 to 7 carbon atoms and heteroatoms as ring atoms.Examples of "heterocycloalkyl" include oxiranyl, thiaranyl, aziridinyl, oxetanyl, thietanyl, azetidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl, tetrahydropyranyl, pyranyl, tetrahydrothiopyranyl, thiopyranyl, piperidinyl, 1,4-dioxanyl, 1,4-oxathianyl, morpholinyl, thiomorpholinyl, 1,4-dithianyl, piperazinyl, 1,4-azathianyl, oxepanyl, thiepanyl, azepanyl, 1,4-dioxepanyl, 1,4-oxathiepanyl, 1,4-oxaazepanyl, 1,4-dithiepanyl, 1,4-thiaazepanyl, 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-benz[d]azepinyl, and the like.

[0046] As used herein, the term "heterocycloalkene ring" means a ring containing one or more heteroatoms selected from atoms other than carbon, such as nitrogen, oxygen, and sulfur, and containing at least one double bond. The "heterocycloalkene ring" may be a monocyclic heterocycloalkene, a fused bicyclic heterocycloalkene, a spiro ring, or a bridged heterocycloalkene 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, the "heterocycloalkene ring having 3 to 7 members" means a heterocycloalkene ring having 3 to 7 ring member atoms including carbon atoms and heteroatoms in total. Examples of the "heterocycloalkene ring" include, but are not limited to, imidazoline, tetrahydropyridine, dihydropyridine, pyran, thiopyran, dihydropyran, dihydrofuran, dihydropyrazine, octahydroquinoline, octahydroisoquinoline, dihydrothiophene, dihydropyrroline, and the like.

[0047] Unless otherwise specified herein, as will be apparent to those skilled in the art, the symbol:

[0048]

Chem.

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

[0050]

Chem.

[0051] means that it is bonded to the near side (β-configuration) of the paper plane. Also, the stereochemical symbols marked with * (e.g., R * , S * etc.) indicate the relative stereoconfiguration of the chiral center. The relative stereoconfiguration is structurally the symbol:

[0052]

Chem.

[0053] is represented by

[0054] In the present specification, "pharmaceutically acceptable" means having no significant toxicity and being usable as a pharmaceutical composition. Thus, in the present specification, "pharmaceutically acceptable salt" means a salt having no significant toxicity and being usable as a pharmaceutical composition.

[0055] In the present invention, "(3RS)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]piperidine-2,6-dione" means the same compound as "3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}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 the same compound as “(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” means the same compound as “(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-dimethyloxane-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 the same compound as “3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}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-dimethyloxane-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 the same compound as “(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” means the same compound as “(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 the same compound as “3-{7-[(1-{[(4R)-2'-fluoro-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]carbonyl}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 the same compound as “(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-dimethyloxane-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 the same compound as “(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-dimethyloxane-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 the same compound as “3-{7-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}piperazin-1-yl)carbonyl]-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxalin-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-dimethyloxetan-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 the same compound as “(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]quinoxalin-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-dimethyloxane-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 the same compound as “(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]quinoxalin-1(2H)-yl}piperidine-2,6-dione”.

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

[0068] [Chemical formula]

[0069] [wherein, A is -O-, -S-, -NR a -, or -CR b R c -, and here, R a is hydrogen, or C 1-3 alkyl, and 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, n Rs 1 are each independently halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, where herein said alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, said cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3 are each independently hydrogen, halogen, C 1-6 alkyl, or C 2-6 alkenyl, where herein said 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, where herein said C 1-6 alkyl is unsubstituted or, 1 to 3 halogens, C 3-7substituted with a cycloalkyl or a 3- to 7-membered heterocycloalkyl, said aryl, heteroaryl, cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, a C 3-7 cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, a C 3-7 cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, wherein, said aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and said aromatic heterocyclic ring, heterocycloalkane ring, and heterocycloalkene ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, L 1 is 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, said alkylene and alkenylene are each independently unsubstituted or substituted with 1 to 3 halogens, ring Q 2 is C 6-12a monocyclic or bicyclic aromatic hydrocarbon ring, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 a cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, C 3-7 a cycloalkene ring, a 3- to 7-membered heterocycloalkene ring, C 5-12 a spirocycloalkane ring, or a 5- to 12-membered spiroheterocycloalkane ring, where herein, the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 5 is C 1-6 alkyl, carboxy, hydroxy, or a group represented by the following formula:

[0070]

Chemical formula

[0071] and n is an integer from 0 to 3], or a pharmaceutically acceptable salt thereof is provided. Herein, the C 1-6 alkyl is unsubstituted or substituted with 1 to 2 groups selected from the group consisting of carboxy, hydroxy, and -O-C 1-6 alkyl, and n is an integer from 0 to 3]. A compound represented by the formula or a pharmaceutically acceptable salt thereof is provided.

[0072] In one aspect of the present invention, A in the above formula (1) is -O-, -S-, or -CR b Rc - and preferably -O- or -CR b R c - and 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 alkyl, preferably hydrogen or methyl, and 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, the n R's in the above formula (1) 1 are each independently 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). In another embodiment of the present invention, the n R's in the above formula (1) 1 are each independently halogen, -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , or a 4- to 6-membered heterocycloalkyl having 1 nitrogen atom as a ring member atom, preferably -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, -N(C 1-3 alkyl) 2 , or a 4- to 6-membered heterocycloalkyl having 1 nitrogen atom as a ring member atom, and more preferably -O-C1-6 is alkyl, more preferably, -O-C 1-3 is alkyl, most preferably, methoxy.

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

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

[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-, -CH 2 -, or -C(=O)-, still 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 monocyclic or bicyclic aromatic hydrocarbon rings of C 3-7 Cycloalkane rings, 3- to 7-membered heterocycloalkane rings (the heterocycloalkane rings having 1 or 2 nitrogen atoms as ring members), 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 1 or 2 nitrogen atoms as ring member atoms). 2 represents a benzene ring optionally substituted with one halogen; 4-7 Cycloalkane ring, optionally substituted with one halogen 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 5 is preferably carboxy, or carboxy, hydroxy and -OC 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, carboxy and hydroxy. 1-6 It is an alkyl.

[0083] In one embodiment of the present invention, in the above formula (1), A is -O-, R 2 is methyl, R 3is methyl, R 4 is C which may be substituted with 1 to 3 halogens, 1-6 alkyl, -C(=O)-C which may be substituted with 1 to 3 halogens, 1-6 alkyl, or 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 a benzene ring which may have 1 substituent selected from the group consisting of halogen and C, 1-3 alkyl, or a pyridine ring, L 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 cycloalkene ring, and a compound or a pharmaceutically acceptable salt thereof is provided.

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

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

[0086] [wherein,

[0087] A is -O- or -CF, A is -O- or -CF, 2 -, R 1is 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 atom, R 2 and R 3 are each independently hydrogen or C 1-6 alkyl, R 4 is C 1-6 alkyl optionally substituted with 1 to 3 halogens, -C(=O)-C 1-6 alkyl optionally substituted with 1 to 3 halogens, C 3-6 cycloalkylmethyl optionally substituted with one trifluoromethyl, or a 6-membered heteroaryl having one or two nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), ring Q 1 is a benzene ring optionally having one or two groups selected from the group consisting of halogen and C 1-3 alkyl, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having one or two nitrogen atoms as ring member atoms, C 4-7 cycloalkane ring, or C 4-7 cycloalkene ring, L 1 is a single bond, -O-, -CH 2 -, or -C(=O)-, ring Q 2 is a benzene ring optionally substituted with one halogen, C 4-7 cycloalkane ring, a C 4-7 cycloalkene ring optionally substituted with one halogen, piperidine ring, or 7-azaspiro[3.5]nonane ring, and R 5 is C 1-6 alkyl optionally having one or two groups selected from the group consisting of carboxy, hydroxy and -O-C 1-6 alkyl, carboxy, hydroxy, or the following formula:

[0088] [Chemical formula]

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

[0090] Since formula (1’) corresponds to a sub-concept of formula (1), all the definitions, explanations, preferred embodiments, etc. of each group in formula (1) above also apply to each group in formula (1’). Further, in this specification, when particularly referring to “the compound represented by formula (1)” without reservation, this means a concept including “the compound represented by formula (1’)”, in other words, “the compounds represented by formula (1) and formula (1’)”.

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

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

[0093] In yet another further aspect of the present invention, the following group: trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid, 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid, {trans-4-[(5-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}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 There is provided any one compound selected therefrom 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. Multifunctional molecule> As described above, since the compound represented by the formula (1) of the present invention or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity, it can be used as a partial structure in a larger molecule (for example, a multifunctional molecule) by combining with other functional moieties. In particular, since the compound represented by the formula (1) of the present invention or a pharmaceutically acceptable salt thereof specifically binds to SF-1, it can be used as an SF-1 binding moiety in a larger molecule (for example, a multifunctional molecule) by combining with other functional moieties.

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

[0096] Since the compound represented by formula (1) is structurally complete in itself, when it is linked to other partial structures, it is necessary to remove a specific atom or atomic group from any position in the compound. For example, when the carboxy group present at the end 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 linkage is structurally different from the compound represented by formula (1) in that the "-OH" portion of the carboxy group has detached. In this specification, thus, the compound represented by formula (1) or a pharmaceutically acceptable salt thereof from which a specific atom or atomic group has dropped out due to the linking reaction is referred to as "a 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 portion or a linker portion for linking to an E3 ligase binding portion) is not particularly limited as long as the functions of the compound represented by formula (1), particularly the SF-1 inhibitory activity and the SF-1 binding activity, can be maintained, but preferably, any position in R 5 can be mentioned. Therefore, in one aspect of the present invention, in the multifunctional molecule of the present invention, the portion corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof is directly linked to other functional portions or linked via a linker at any position in R 5 . As any position in R 5 , preferably, the carboxy portion or the amine portion in R 5 can be mentioned.

[0098] In the present invention, the "multifunctional molecule" means a molecule containing a moiety having two or more specific functions (functionalities). As described above, since the moiety corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof has SF-1 antagonist activity and SF-1 binding activity, the multifunctional molecule of the present invention further contains at least one other functional moiety having a specific function. When there is one other functional moiety, the multifunctional molecule of the present invention is a "bifunctional molecule", and when there are two, three, and four other functional moieties, the multifunctional molecules of the present invention are a "trifunctional molecule", a "tetrafunctional molecule", and 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. Further, the other functional moiety may be a moiety having the same function as the moiety corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof, or may be a moiety having a different function. Therefore, in one aspect of the present invention, the multifunctional molecule is a homomultifunctional molecule, and in another aspect, the multifunctional molecule is a heteromultifunctional molecule. In one aspect of the present invention, the multifunctional molecule of the present invention is preferably a hetero-bifunctional molecule or a hetero-trifunctional molecule, and more preferably a hetero-bifunctional molecule.

[0099] Other functional moieties included in the multifunctional molecules of the present invention are not particularly limited, but those that can reasonably be expected to have beneficial effects such as enhancing or complementing the activity when linked to a moiety having SF-1 inhibitory / binding activity are preferred. Examples of such other functional moieties include, but are not limited to, an E3 ligase-binding moiety (or an E3 ligase-recruiting moiety), an autophagy-recruiting moiety, a lysosome-recruiting moiety, a kinase-recruiting moiety, a phosphatase-recruiting moiety, a glycosyltransferase-recruiting moiety, or an acetyltransferase-recruiting moiety, an ADC, etc. Further, as such other functional moieties, substances useful only for research purposes, such as specific molecular markers or radioactive labels, can be employed, or functional substituents for converting the compound of formula (1) into a prodrug can also be employed.

[0100] In the present invention, the "binding moiety" (e.g., "E3 ligase-binding moiety") means a moiety that binds to a target (e.g., "E3 ligase"), and the "recruiting moiety" (e.g., "E3 ligase-recruiting moiety") means a moiety that enables recruitment of a target (e.g., "E3 ligase"). Since the moiety that binds to a target can be used to recruit the target, in one aspect of the present invention, the "binding moiety" and the "recruiting 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 an E2 ubiquitin-conjugating enzyme carrying ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin from the E2 protein to the substrate. A multifunctional molecule in which a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof is linked to an E3 ligase-binding portion can induce the degradation of SF-1. Therefore, in one aspect of the present invention, there is provided a multifunctional molecule comprising a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof, and other functional portions, wherein the portion corresponding to the compound or a pharmaceutically acceptable salt thereof is directly linked to the other functional portions at any position in R 5 or is linked via a linker, and the other functional portion is an E3 ligase-binding portion. Without intending to be bound by theory, when a multifunctional molecule in which a portion corresponding to the compound represented by formula (1) of the present invention or a pharmaceutically acceptable salt thereof is linked to an E3 ligase-binding portion is administered in vivo, the multifunctional molecule recruits both SF-1 and the E3 ligase, thereby forming a ternary complex composed of SF-1, the E3 ligase, and the multifunctional molecule, and it is considered that SF-1 can be ubiquitinated by placing SF-1 and the E3 ligase in close proximity. Since ubiquitinated SF-1 is degraded by the endogenous proteasome system, the multifunctional molecule of the present invention containing an E3 ligase-binding portion is considered to be able to induce specific degradation of SF-1.

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

[0103] In the TPD platform, the POI-binding moiety and the E3 ligase-binding moiety each play substantially independent and distinct roles. Therefore, when combining each block (part) that has been demonstrated to function, there is a high probability of obtaining the desired effect. Thus, as the E3 ligase-binding moiety (or the combination of the ligase-binding moiety and the linker moiety) in the multifunctional molecule of the present invention, the E3 ligase-binding moiety (or the combination of the ligase-binding moiety and the linker moiety) of any target proteolysis inducer that has been confirmed to be useful so far can be applied. For example, the E3 ligase-binding moiety (or the combination of the ligase-binding moiety and the linker moiety) disclosed in Patent Documents 1-9 and Non-Patent Documents 7-9 can be applied. In addition, the E3 ligase-binding moiety (or the combination of the ligase-binding moiety and the linker moiety) in hetero-bifunctional 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, CFT8919, etc., which have been reported to be used in clinical trials or pre-clinical trials, can also be applied.In other words, the portion corresponding to the compound of formula (1) of the present invention or a pharmaceutically acceptable salt thereof is the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) of any target proteolysis inducer that has been confirmed to be useful so far. For example, the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) disclosed in Patent Documents 1-8, Non-Patent Documents 7-9, etc., or the E3 ligase binding portion (or a combination of the ligase binding portion and the linker portion) in hetero-bifunctional 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, CFT8919. When linked, although there may be a difference in the degree of activity, it can be reasonably expected to obtain a polyfunctional molecule (particularly, a hetero-bifunctional molecule) having the desired SF-1 degradation activity.

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

[0105] As the "CRBN binding moiety" in the present invention, any compound moiety having any structure can be used without limitation as long as it exhibits the intended binding property to CRBN. For example, the CRBN binding moieties disclosed in Patent Documents 1-9 and Non-Patent Documents 7-9 can be exemplified. For example, thalidomide and its derivatives lenalidomide and pomalidomide are known to exhibit binding properties 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 "derivative" in the context of the E3 ligand binding moiety means a compound that has a structural difference compared to the parent E3 ligand binding molecule but maintains the intended binding activity to the target E3 ligase, or has a higher binding activity to the target E3 ligase. Also, as target protein degraders or proteolysis targeting chimeras (PROTACs) containing a CRBN binding moiety, compounds named ARV-471, ARV-110, CFT8634, CFT7455, CFT1946, AR-LDD, NX-2127, KT-413, NX-5948, CG001419, and CFT8919 are being subjected to clinical trials or preclinical trials. Therefore, in one aspect of the present invention, the CRBN binding moiety may be the CRBN binding moiety in these compounds.

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

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

[0108] In one aspect of the present invention, examples of the cIAP binding moiety 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 derivatives thereof.

[0109] In one aspect of the present invention, examples of the DCAF11 binding moiety 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, examples of the DCAF15 binding moiety include E7820 (L. Snyder, American Association for Cancer Research Annual Meeting, April 2021), or derivatives thereof.

[0111] In one aspect of the present invention, examples of the DCAF16-binding moiety include KB02 (G. Weng, et al., Nucleic Acids Res., 2021, 49, D1381-D1387), or derivatives thereof.

[0112] In one aspect of the present invention, examples of the MDM2-binding moiety 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 derivatives thereof.

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

[0114] In one aspect of the present invention, examples of the RNF4-binding moiety include CCW-16 (I. Sosic, et al., Chem. Soc. Rev., 2022, 51, 3487-3534), or derivatives thereof.

[0115] In one aspect of the present invention, examples of the RNF114-binding moiety 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 derivatives thereof.

[0116] In one aspect of the present invention, examples of the AhR binding moiety include beta-NF (K. Li and C. M. Crews, Chem. Soc. Rev., 2022, 51, 5214-5236) or derivatives thereof.

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

[0118] In addition, as the E3 ligase binding moiety in the present invention, any structure defined as "R" in the formula represented by formula (2) described later can also be adopted. 6 」can also adopt any of the structures defined as such.

[0119] <5. Linker> In the multifunctional molecule 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 other functional moieties as long as it exhibits the intended function (for example, SF-1 inhibitory activity or SF-1 degrading activity), but it is preferably linked via a linker. Therefore, in one aspect of the present invention, the moiety corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof and other functional moieties (for example, the E3 ligase binding moiety) are either directly linked or linked via a linker, and preferably, a multifunctional molecule linked via a linker is provided. The linker used in the multifunctional molecule of the present invention is not particularly limited as long as it does not impair the intended function (for example, SF-1 inhibitory activity or SF-1 degrading activity). Thus, a linker having any structure that can reasonably be expected not to impair the intended function (for example, SF-1 inhibitory activity or SF-1 degrading activity) can be adopted.

[0120] As described above, in the TPD platform, it is known that the composition and length of the linker can affect the formation of a ternary complex of POI / heterobifunctional molecule / E3 ligase, the activity of inducing the degradation of POI, and target selectivity. Many reports have been made on the linker structures used in target protein degradation inducers and the technical theories for designing and optimizing them (for example, Patent Documents 1-8, Non-Patent Documents 7-9). As described above, since the present invention presents a novel POI-binding moiety that can be used in such a TPD platform, when a linker that has already proven effective is adopted, the probability of obtaining the desired effect is high. Therefore, in one aspect of the present invention, as the linker moiety in the multifunctional molecule of the present invention, the linker moieties of any target protein degradation inducer that has been confirmed to be useful so far can be used. For example, the linker moieties disclosed in Patent Documents 1-8, 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 used in clinical trials or preclinical trials, can be applied. For example, in one aspect of the present invention, the linker has the linker structure shown in Table 2 of Non-Patent Document 8, specifically, the following formula:

[0121]

Chemical formula

[0122] It may be selected from those having any structural motif represented by (wherein n and m each independently represent an integer from 1 to 10). Generally, when a linker that is too short is used, the formation efficiency of the ternary complex (POI / heterobifunctional molecule / E3 ligase) decreases. Instead, the formation orientation of the binary complex (POI / heterobifunctional molecule, or heterobifunctional molecule / E3 ligase) tends to increase. On the other hand, when a linker that is too long is used, the spatial freedom increases, the formation efficiency of the ternary complex decreases, and furthermore, the stability of the entire molecule tends to decrease. Therefore, it is preferable to adopt a linker having an appropriate length as the linker in the present invention. From the above viewpoints, in one aspect of the present invention, n and m in the above formula are each independently an integer from 1 to 5. In another aspect of the present invention, n and m in the above formula are each independently an integer from 1 to 4. In still another aspect of the present invention, n and m in the above formula are each independently an integer from 1 to 3. In still another aspect 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 also known that the binding positions of the linker to the POI or the linker to the E3-ligase can also affect the formation of the ternary complex of POI / heterobifunctional molecule / E3-ligase, the decomposition-inducing activity of the POI, and the target selectivity. As the binding position of the linker, generally, it is considered important not to link the linker to the main active site of the POI-binding part or the E3-ligase-binding part, and to link the linker to the solvent-exposed site in the POI-binding part or the E3-ligase-binding part. From such a viewpoint, in the multifunctional molecule of the present invention, the part corresponding to the compound represented by formula (1) or a pharmaceutically acceptable salt thereof is preferably linked to the linker at any position in R 5 and particularly preferably linked to the linker at the carboxy part or the amine part in R 5 . Also, at the connection point between the linker and the E3-ligase binding part, it is preferable to appropriately select from the above viewpoints with reference to known reports.

[0124] In one aspect of the present invention, the linker of the present invention is "-L" as defined in formula (2) described below. 2 -L 3 -L 4 -".

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

[0126]

Chemical formula

[0127] [In the formula, A is -O-, -S-, -NR a -, or -CR b R c -. Here, R a is hydrogen or C 1-3 alkyl. R b and R c are each independently hydrogen, halogen, or C 1-3 alkyl. The alkyl is unsubstituted or substituted with 1 to 3 halogens. n R 1 are each independently halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl. Here, The alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens. The cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3 are each independently hydrogen, halogen, 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 the C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens, C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, ring Q 1 is C 6-12a monocyclic or bicyclic aromatic hydrocarbon ring, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 a cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, C 3-7 a cycloalkene ring, or a 3- to 7-membered heterocycloalkene ring, and wherein the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, and heterocycloalkene ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, L 1 is 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 a C 6-12 monocyclic or bicyclic aromatic hydrocarbon ring, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 a cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, C 3-7 a cycloalkene ring, a 3- to 7-membered heterocycloalkene ring, C 5-12 a spirocycloalkane ring, or a 5- to 12-membered spiroheterocycloalkane ring, wherein The aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, B is -L 2 -L 3 -L 4 -R 6 wherein, L 2 is a single bond, C 1-6 alkylene, -C(=O)-, -C(=O)NH-, -(CH 2 ) k -C(=O)NH- (k represents an integer from 1 to 3), or -NHC(=O)-, L 3 is a single bond, C 1-6 alkylene, C 3-6 cycloalkylene, piperazinediyl, piperazine-2-one diyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonane diyl, L 4 is a single bond, -NH-, -N(-R 7 )- (R 7 represents 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, There is provided a compound represented by n being an integer from 0 to 3 or a pharmaceutically acceptable salt thereof.

[0128] In one aspect 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 -, particularly preferably -O-.

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

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

[0131] In one aspect of the present invention, the n R 1 in the above formula (2) are each independently 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). In another aspect of the present invention, the n R 1 in the above formula (1) are each independently halogen, -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , or a 4- to 6-membered heterocycloalkyl having 1 nitrogen atom as a ring member atom, preferably -O-C1-6 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 1-6 alkyl which may be substituted with 1 to 3 halogens, still more preferably -O-C 1-3 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 alkyl, more preferably methyl or ethyl, and still 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 alkyl, more preferably methyl or ethyl, and still more preferably methyl.

[0134] In one embodiment of the present invention, R in the above formula (2) 4 is each unsubstituted or C 3-7 cycloalkyl-substituted C 1-6 alkyl, -C(=O)-C 1-6 alkyl, or a 6- to 12-membered heteroaryl (the heteroaryl has 1 or 2 nitrogen atoms as ring member atoms). In another embodiment of the present invention, R in the above formula (2) 4 is C 1-6 alkyl which may be substituted with 1 to 3 halogens, -C(=O)-C 1-6 alkyl which may be substituted with 1 to 3 halogens, C 3-6Cycloalkylmethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with 1 halogen), preferably C which may be substituted with 1 to 3 halogens 1-6 Alkyl, -C(=O)-C which may be 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 which may be substituted with 1 to 3 halogens 1-6 Alkyl, and most preferably 3,3,3-trifluoro-2,2-dimethylpropyl.

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

[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-, -CH 2 -, or -C(=O)-, still more preferably a single bond, -O-, or -C(=O)-, and particularly preferably a single bond.

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

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

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

[0142]

Chemical formula

[0143] (wherein the wavy line indicates the bonding position with Q 2 and R 6 and represents any structure selected from the groups represented by).

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

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

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

[0147] [Chemical formula]

[0148] [wherein, A is -O- or -CF 2 -, R 1 is halogen, -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, -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, R 2 and R 3 are each independently hydrogen or C 1-6 alkyl, R 4 is C 1-6 alkyl which may be substituted with 1 to 3 halogens, -C(=O)-C 1-6 alkyl which may be substituted with 1 to 3 halogens, C 3-6 cycloalkylmethyl which may be substituted with one trifluoromethyl, or a 6-membered heteroaryl having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl may be substituted with one halogen), ring Q 1 is a benzene ring which may have 1 or 2 groups selected from the group consisting of halogen and C 1-3 alkyl, a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring having 1 or 2 nitrogen atoms as ring member atoms, C 4-7 cycloalkane ring, or C 4-7 cycloalkene ring, L 1 is a single bond, -O-, -CH 2 -, or -C(=O)-, ring Q 2 is a benzene ring which may be substituted with one halogen, C 4-7 cycloalkane ring, C 4-7 cycloalkene ring which may be substituted with one halogen, piperidine ring, or 7-azaspiro[3.5]nonane ring, B is -L 2 -L 3 -L 4 -R 6 wherein, L 2 is a single bond, C 1-6 alkylene, -C(=O)-, -C(=O)NH-, -(CH 2 ) k -C(=O)NH- (k represents an integer from 1 to 3), or -NHC(=O)-, L 3is a single bond, C 1-6 alkylene, C 3-6 cycloalkylene, piperazinediyl, piperazine-2-one diyl, piperidinediyl, pyrrolidinediyl, azetidinediyl, or 3-oxa-9-azabicyclo[3.3.1]nonanediy, and L 4 is a single bond, -NH-, -N(-R 7 ),-(R 7 represents 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 a compound represented thereby or a pharmaceutically acceptable salt thereof is provided.

[0149] Since formula (2') corresponds to a sub-concept of formula (2), all definitions, explanations, preferred embodiments, etc. for each group in the above formula (2) also apply to each group in formula (2'). Further, in this specification, when particularly referring to "a compound represented by formula (2)" without reservation, this includes the concept of "a compound represented by formula (2')", in other words, it means "a compound represented by formula (2) and formula (2')".

[0150] In one aspect of the present invention, R 6 in the above formula (2) and formula (2') is an E3 ligase binding moiety, and in another aspect of the present invention, R 6 in the above formula (2) and formula (2') is a CRBN binding moiety. Regarding the E3 ligase binding moiety or CRBN binding moiety that can be used as R 6 , the references in the above <3. E3 ligase binding moiety> can be applied as they are.

[0151] In another aspect of the present invention, R 6is the following formula:

[0152] [Chemical formula]

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

[0154] In yet another further aspect of the present invention, R 6 in the above formulas (2) and (2') is the following formula:

[0155] [Chemical formula]

[0156] [wherein, R 8 is hydrogen or C 1-6 alkyl, V is a halogen, and the wavy line indicates the bonding position with L 4 and is any group selected from].

[0157] In one aspect of the present invention, in the above formulas (2) and (2'), R 1 is -O-C 1-6 alkyl which may be substituted with 1 to 3 halogens, R 4 is C 1-6Alkyl, or a C optionally substituted with one trifluoromethyl 3-6 is cycloalkylmethyl, ring Q 1 is a benzene ring optionally having one or two groups selected from the group consisting of halogen and C 1-6 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 cycloalkene ring, and L 1 is a single bond or -O-, there is provided a compound or a pharmaceutically acceptable salt thereof.

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

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

[0160] In one aspect of the present invention, in the above formulas (2) and (2'), ring Q 1 is a benzene ring optionally having one halogen, L 1 is a single bond, and ring Q 2 is a cyclohexene ring, there is provided a compound or a pharmaceutically acceptable salt thereof.

[0161] In another aspect of the present invention, the following group: 3-{5-[(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[biphenyl]-4-yl]methyl}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]quinoxalin-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]quinoxalin-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]quinoxalin-1(2H)-yl}piperidine-2,6-dione There is provided any one compound selected from the group consisting of or a pharmaceutically acceptable salt thereof. These compounds all correspond to the compound represented by the above formula (2) or a pharmaceutically acceptable salt thereof.

[0162] In another aspect of the present invention, the compound represented by the formula (2) or a pharmaceutically acceptable salt thereof may be in the form of their crystals. Therefore, in one aspect of the present invention, there is provided a crystal of the compound represented by the formula (2) or a pharmaceutically acceptable salt thereof. The crystal can be produced according to 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 the crystal may generally be carried out by a method 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 about ±0.2° 2θ. For example, hydrates and anhydrates may change their lattice constants due to the attachment and detachment of crystal water, which may also cause a change in the diffraction angle (2θ) in powder X-ray diffraction. The intensity of the diffraction peak may also change due to differences such as the crystal growth face (crystal habit). Therefore, when the crystal of the present invention is represented based on the powder X-ray diffraction data, in addition to the crystal in which the diffraction angle of the peak and the X-ray diffraction pattern in powder X-ray diffraction are identical, hydrates and anhydrates obtained therefrom are also included in the scope of the present invention.

[0164] In one aspect of the present invention, the crystal is a crystal of (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, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 2.15 ± 0.2, 8.30 ± 0.2, 10.29 ± 0.2, 14.75 ± 0.2, 17.19 ± 0.2, 20.00 ± 0.2, 21.34 ± 0.2, 22.68 ± 0.2, 23.77 ± 0.2, and 25.23 ± 0.2.

[0165] In one aspect of the present invention, the crystal is a crystal of (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, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 2.21 ± 0.2, 12.04 ± 0.2, 14.87 ± 0.2, 17.69 ± 0.2, 18.93 ± 0.2, 20.41 ± 0.2, 22.42 ± 0.2, 23.19 ± 0.2, 24.13 ± 0.2, and 27.98 ± 0.2.

[0166] In one aspect of the present invention, the crystal is a crystal of (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, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 3.89 ± 0.2, 6.81 ± 0.2, 7.68 ± 0.2, 8.20 ± 0.2, 10.28 ± 0.2, 13.15 ± 0.2, 15.97 ± 0.2, 16.81 ± 0.2, 18.58 ± 0.2, and 23.56 ± 0.2.

[0167] In one aspect of the present invention, the crystal is a crystal of (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 ethanesulfonate, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 2.27 ± 0.2, 8.18 ± 0.2, 9.88 ± 0.2, 13.09 ± 0.2, 14.57 ± 0.2, 15.80 ± 0.2, 16.91 ± 0.2, 17.77 ± 0.2, 18.87 ± 0.2, and 20.14 ± 0.2.

[0168] In one aspect of the present invention, the crystal is a crystal of (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, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 2.20 ± 0.2, 4.34 ± 0.2, 9.45 ± 0.2, 10.97 ± 0.2, 13.23 ± 0.2, 16.98 ± 0.2, 18.09 ± 0.2, 20.20 ± 0.2, 21.32 ± 0.2, and 25.19 ± 0.2.

[0169] In one aspect of the present invention, the crystal is a crystal of (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, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα ray (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 2.19 ± 0.2, 8.87 ± 0.2, 10.86 ± 0.2, 12.55 ± 0.2, 13.05 ± 0.2, 14.99 ± 0.2, 17.84 ± 0.2, 20.62 ± 0.2, 21.43 ± 0.2, and 25.27 ± 0.2.

[0170] In one embodiment of the present invention, the crystal is a crystal of (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, and in the powder X-ray diffraction pattern obtained by irradiation with copper Kα rays (λ = 1.54 Å), it is a crystal having peaks at diffraction angles (2θ) of 2.20 ± 0.2, 7.82 ± 0.2, 11.05 ± 0.2, 12.42 ± 0.2, 13.34 ± 0.2, 15.23 ± 0.2, 16.49 ± 0.2, 17.86 ± 0.2, 20.15 ± 0.2, and 24.36 ± 0.2.

[0171] <7. Salt, isomer, prodrug, etc.> The "pharmaceutically acceptable salt" in the present invention means a salt that can be used as a medicine. When the compound or polyfunctional molecule of the present invention has an acidic group, a basic salt (also referred to as "base addition salt") can be formed by reacting with a base, and when it has a basic group, an acidic salt (also referred to as "acid addition salt") can be formed by reacting with an acid. Therefore, in one embodiment of the present invention, the pharmaceutically acceptable salt of the compound represented by formula (1) or the compound represented by formula (2) is a basic salt, and in another embodiment of the present invention, the pharmaceutically acceptable salt of the compound represented by formula (1) or the compound represented by formula (2) is an acidic salt.

[0172] As the "basic salt" in the present invention, preferably, 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; or amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate salt, and aspartate salt can be mentioned.

[0173] As the "acidic salt" in the present invention, preferably, hydrohalic acid salts such as hydrofluoride salt, hydrochloride salt, hydrobromide salt, and hydroiodide salt, inorganic acid salts such as nitrate salt, perchlorate salt, sulfate salt, and phosphate salt; lower alkanesulfonate salts such as methanesulfonate salt, trifluoromethanesulfonate salt, and ethanesulfonate salt, arylsulfonate salts such as benzenesulfonate salt and p-toluenesulfonate salt, organic acid salts such as acetate salt, malate salt, fumarate salt, succinate salt, citrate salt, ascorbate salt, tartrate salt, oxalate salt, and maleate salt; or amino acid salts such as glycine salt, lysine salt, arginine salt, ornithine salt, glutamate salt, and aspartate salt can be mentioned.

[0174] The compound of the present invention or its pharmaceutically acceptable salt may take in water molecules and become a hydrate by being left in the air or recrystallized, and such hydrates are also included in the present invention. Further, the compound of the present invention or its pharmaceutically acceptable salt may absorb a certain kind of solvent and become a solvate by being left in a solvent or recrystallized, and such solvates are also included in the present invention. Furthermore, the compound of the present invention or its pharmaceutically acceptable salt can exist as an amorphous substance or as a crystalline substance.

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

[0176] The compounds of the present invention, pharmaceutically acceptable salts thereof, or solvates thereof may have various isomers such as geometric isomers (e.g., cis and trans isomers), tautomers, rotational isomers, optical isomers (including enantiomers and diastereomers such as d-form and l-form) depending on the type and combination of substituents. The compounds of the present invention include all such isomers, stereoisomers, and mixtures of these isomers and stereoisomers in any ratio, unless otherwise particularly limited. Mixtures of these isomers can be separated by known separation means.

[0177] In addition, the present invention also includes prodrugs of the compounds represented by formula (1) or formula (2). A prodrug is a compound having a group that can be converted into an amino group, a hydroxy group, a carboxy group, etc. of a compound by hydrolysis or under physiological conditions. Examples of groups that form such prodrugs include those described in Prog. Med., Vol. 5, pages 2157-2161, 1985, etc. More specifically, as the prodrug, (1) When the compound has an amino group, examples of the compound in which the amino group is acylated, alkylated, or phosphorylated include compounds in which the amino group is eicosanoylated, alanylated, pentylaminocarbonylated, (5-methyl-2-oxo-1,3-dioxolen-4-yl)methoxycarbonylated, tetrahydrofuranylated, pyrrolidylmethylated, pivaloyloxymethylated, tert-butylated, etc. (2) When the compound has a hydroxyl group, examples of the compound in which the hydroxy group is acylated, alkylated, phosphorylated, or borated include compounds in which the hydroxy group is acetylated, palmitoylated, propanoylated, pivaloylated, succinylated, fumarylated, alanylated, or dimethylaminomethylcarbonylated, etc. (3) When the compound has a carboxy group, examples of the compound in which the carboxy group is esterified or amidated include compounds in which the carboxy group is ethyl esterified, phenyl esterified, carboxymethyl esterified, dimethylaminomethyl esterified, pivaloyloxymethyl esterified, ethoxycarbonyloxyethyl esterified, amidated, or methylamidated, etc.

[0178] <8. Composition and Pharmaceutical Use> 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, which contains 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. In another aspect of the present invention, there is provided a method for treating a disease, which comprises administering an effective amount of 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 to a subject in need of treatment for the disease. 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 treatment of a disease. In addition, 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 the treatment of a disease.

[0179] In the present invention, the "composition for inhibiting SF-1" means a composition aimed at inhibiting SF-1. Inhibition of SF-1 typically means inhibiting the physiological activity of SF-1, and in particular, blocking or attenuating the expression of genes transcriptionally regulated by SF-1. As an aspect of inhibiting SF-1, there is an aspect of blocking or attenuating the transcriptional induction activity of downstream genes by SF-1 by directly binding to SF-1. However, there is also an aspect of blocking or attenuating the physiological activity of SF-1 as a result of acting on a protein upstream of SF-1 without directly binding to SF-1. The "composition for inhibiting SF-1" includes not only a composition aimed only at inhibiting SF-1, but also those including inhibition of SF-1 as one of its purposes. The "composition for inhibiting SF-1" can typically include those in which inhibition of SF-1 is listed as one of the uses in the attached documents, packages, promotional materials, etc. of the composition. However, even without such an explicit indication, those substantially including inhibition of SF-1 as one of the uses are also included.

[0180] In the present invention, the "composition for inducing degradation of SF-1" means a composition aimed at inducing degradation of SF-1. The "composition for inducing degradation of SF-1" includes not only a composition aimed only at inducing degradation of SF-1, but also those including induction of degradation of SF-1 as one of its purposes. The "composition for inducing degradation of SF-1" can typically include those in which induction of degradation of SF-1 is listed as one of the uses in the attached documents, packages, promotional materials, etc. of the composition. However, even without such an explicit indication, those substantially including induction of degradation of SF-1 as one of the uses are also included.

[0181] In the present invention, the "pharmaceutical composition" means a composition used for the treatment / prevention of any disease. Since the compound or multifunctional molecule of the present invention has SF-1 antagonist activity, it can be used as a composition for the treatment and / or prevention of diseases in which SF-1 is involved in its occurrence and progression. Such diseases include, but are not limited to, castration-resistant prostate cancer, adrenocortical cancer, Leydig tumor, hormone-sensitive prostate cancer, cancers such as breast cancer, Cushing's syndrome, and primary aldosteronism. Therefore, in one aspect of the present invention, the pharmaceutical composition of the present invention is for treating castration-resistant prostate cancer, adrenocortical cancer, 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 cancer. 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 cancer.

[0182] As the administration route of such a composition to humans or other animals, oral administration by tablets, pills, capsules, granules, powders, liquids, etc., or parenteral administration by injections for intra-articular, intravenous, intramuscular, etc., suppositories, eye drops, eye ointments, transdermal liquids, ointments, transdermal patches, transmucosal liquids, transmucosal patches, inhalants, etc. may be used. However, considering that the molecular weight of the compound or multifunctional molecule of the present invention is not extremely large, oral administration is preferred from the viewpoint of reducing the medication burden.

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

[0184] Examples of liquid compositions for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, elixirs, and the like. In such liquid compositions, it is possible to add commonly used inert diluents, such as purified water or ethanol. Such liquid compositions may also contain, in addition to the inert diluent, auxiliary agents such as solubilizing agents and wetting agents, sweeteners, flavoring agents, fragrances, preservatives, and the like.

[0185] Examples of injectable preparations for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions, emulsions, and the like. Examples of aqueous solvents include distilled water for injection, physiological saline, and the like. Examples of non-aqueous solvents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, alcohols such as ethanol, polysorbate 80, and the like. Such injectable compositions may further contain isotonic agents, preservatives, wetting agents, emulsifying agents, dispersing agents, stabilizers, solubilizing aids, and the like. These injectable compositions can be sterilized, for example, by filtration through a bacteria-retaining filter, incorporation of a bactericide, or irradiation. Also, these injectable compositions can be prepared by manufacturing a sterile solid composition and dissolving or suspending it in sterile water or a sterile injectable solvent before use.

[0186] Examples of external preparations include ointments, plasters, creams, jellies, poultices, sprays, lotions, eye drops, eye ointments, etc. These external preparations may generally contain commonly used ointment bases, lotion bases, aqueous or non-aqueous liquids, suspensions, emulsions, etc. For example, as ointment or lotion bases, polyethylene glycol, propylene glycol, white petrolatum, purified beeswax, polyoxyethylene hydrogenated castor oil, glyceryl monostearate, stearyl alcohol, cetyl alcohol, laureth, sorbitan sesquioleate, etc. can be mentioned.

[0187] Transmucosal agents such as inhalants and nasal preparations can be in solid, liquid, or semi-solid form and can be manufactured according to conventionally known methods. For example, known excipients, and further, pH adjusters, preservatives, surfactants, lubricants, stabilizers, thickeners, etc. may be appropriately added. In these transmucosal agents, as the administration method, a device suitable for inhalation or insufflation can be used. For example, using a known device such as a metered-dose inhaler or a nebulizer, the compound or multifunctional molecule can be administered 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, etc. can be for single or multiple administrations, and dry powder or powder-containing capsules can be used. Alternatively, a suitable propellant can also be used. For example, it may be in the form of a pressurized aerosol spray using a suitable gas such as chlorofluorocarbon, hydrofluorocarbon, carbon dioxide, etc.

[0188] The composition of the present invention may contain other active ingredients, or can be used in combination with another composition containing other active ingredients. Such combination use may be simultaneous administration, or separately and continuously, or at desired time intervals. The simultaneous administration preparation may be a compound preparation or separately formulated.

[0189] The filling amount of the compound or the composition of the polyfunctional molecule of the present invention into a composition or the dosage amount administered to a subject is not particularly limited as long as it is an effective amount for achieving the purpose, and can be appropriately selected according to the purpose of use, the age, weight, symptoms, health status, disease progression status, etc. of the subject. There is also no particular limitation on the dosing frequency, which can be appropriately selected according to the purpose. For example, the daily dosage amount may be administered once a day or divided into multiple doses.

[0190] In the present invention, the "effective amount" or "therapeutically effective amount" means an amount effective for treating, preventing progression of, or alleviating existing symptoms of the subject to be treated. The determination of the effective amount can be appropriately carried out according to conventional methods with reference to the intended therapeutic effect and side effects.

[0191] <9. Combination Use> 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 used in combination with other antitumor agents. Examples of other antitumor agents include, for example, alkylating agents, antimetabolites, antitumor antibiotics, microtubule inhibitors, topoisomerase inhibitors, BRMs (biological response modifiers), hormonal agents, vitamins, antitumor antibodies, molecular target drugs, and other antitumor agents.

[0192] More specifically, examples of alkylating agents include alkylating agents such as nitrogen mustard, nitrogen mustard-N-oxide, chlorambucil; aziridine-based alkylating agents such as carbocon, thiotepa; epoxide-based alkylating agents such as dibromomannitol, dibromodulcitol; nitrosourea-based alkylating agents such as carmustine, lomustine, semustine, nimustine hydrochloride, streptozocin, chlorozotocin, ranimustine; busulfan; improsulfan tosylate; dacarbazine, etc.

[0193] Examples of various metabolic antagonists include purine metabolic antagonists such as 6-mercaptopurine, 6-thioguanine, and thioinosine; pyrimidine metabolic antagonists such as fluorouracil, tegafur, tegafur-uracil, carmofur, doxifluridine, broxuridine, cytarabine, enocitabine, and capecitabine; folic acid metabolic antagonists such as methotrexate, trimetrexate, and pemetrexed; and active folic acid agents such as levofolinic acid, etc.

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

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

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

[0197] Examples of BRM include tumor necrosis factor, indomethacin, etc.

[0198] Examples of hormonal agents include hydrocortisone, cortisone acetate, fludrocortisone, fludrocortisone acetate, dexamethasone, methylprednisolone, prednisone, plastolone, betamethasone, triamcinolone, oxymetholone, nandrolone, methenolone, phosphoestrol, ethinyl estradiol, chlormadinone, glucocorticoid, medroxyprogesterone, bicalutamide, enzalutamide, apalutamide, goserelin, leuprorelin, tamoxifen, degarelix, mitotane, tamoxifen, and the like.

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

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

[0201] Examples of other anti-tumor agents include platinum compounds such as cisplatin, carboplatin, oxaliplatin; ifosfamide, cyclophosphamide, melphalan, L-asparaginase, aceglutamide, sizofiran, picibanil, procarbazine, pipobroman, neocarzinostatin, hydroxyurea, ubenimex, krestin, and the like.

[0202] In addition, 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 used in combination with an antibody-drug conjugate (ADC) containing the above other antitumor agent as a payload or a target protein degradation inducer using the above other antitumor agent as a POI ligand.

[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 at intervals from the above combined drug, and may be in the form of a combined preparation or a kit preparation.

[0204] In the treatment of adrenocortical cancer, antitumor agents preferably used in combination with 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 include anthracycline compounds such as doxorubicin; platinum compounds such as cisplatin and carboplatin; antitumor antibodies such as nivolumab, pembrolizumab, and camrelizumab; molecular target drugs such as eganelisib, apatinib, cabozantinib, and OR-449; mitotane; and etoposide, and one or more selected therefrom.

[0205] In the treatment of castration-resistant prostate cancer, antitumor agents preferably used in combination with 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 include hormonal agents such as abiraterone, enzalutamide, goserelin, and apalutamide; microtubule inhibitors such as docetaxel and cabazitaxel; PARP inhibitors such as olaparib and rucaparib; androgen receptor degradation inducers such as ARV-110, ARV-766, and CC-94676; CYP11A1 enzyme inhibitors such as ODM-208; and antitumor antibodies such as nivolumab, pembrolizumab, and camrelizumab, and one or more selected therefrom.

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

[0207]

Chemical formula

[0208] [wherein, A is -O-, -S-, -NR a -, or -CR b R c -, here, 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, n R 1 are each independently halogen, hydroxy, -CN, C 1-6 alkyl, C 2-6 alkenyl, -O-C 1-6 alkyl, -N(H)-C 1-3 alkyl, -N(C 1-3 alkyl) 2 , C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, here, the alkyl and alkenyl are each independently unsubstituted or substituted with 1 to 3 halogens, the cycloalkyl and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 2 and R 3is, independently of each other, hydrogen, halogen, C 1-6 alkyl, or C 2-6 alkenyl, and where 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, and where the C 1-6 alkyl is unsubstituted or substituted with 1 to 3 halogens, C 3-7 cycloalkyl, or 3- to 7-membered heterocycloalkyl, the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the heteroaryl and heterocycloalkyl have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, ring Q 1 is a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 cycloalkane ring, 3- to 7-membered heterocycloalkane ring, C 3-7 cycloalkene ring, or 3- to 7-membered heterocycloalkene ring, and where the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, and heterocycloalkene ring are each independently unsubstituted or substituted with halogen, unsubstituted C1-3 is substituted with 1 to 3 groups selected from the group consisting of alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, and heterocycloalkene ring each have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, L 1 is 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 a monocyclic or bicyclic aromatic hydrocarbon ring of C 6-12 , a 6- to 12-membered monocyclic or bicyclic aromatic heterocyclic ring, C 3-7 cycloalkane ring, a 3- to 7-membered heterocycloalkane ring, C 3-7 cycloalkene ring, a 3- to 7-membered heterocycloalkene ring, C 5-12 spirocycloalkane ring, or a 5- to 12-membered spiroheterocycloalkane ring, wherein the aromatic hydrocarbon ring, aromatic heterocyclic ring, cycloalkane ring, heterocycloalkane ring, cycloalkene ring, heterocycloalkene ring, spirocycloalkane ring, and spiroheterocycloalkane ring are each independently unsubstituted or substituted with 1 to 3 groups selected from the group consisting of halogen, unsubstituted C 1-3 alkyl and C 1-3 haloalkyl, and the aromatic heterocyclic ring, heterocycloalkane ring, heterocycloalkene ring, and spiroheterocycloalkane ring each have 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, R 10 is C 1-6 alkyl, wherein said C 1-6 alkyl is substituted with 1 or 2 3- to 7-membered heterocycloalkyls, said heterocycloalkyl has 1 or 2 heteroatoms selected from oxygen, nitrogen, and sulfur as ring member atoms, and said heterocycloalkyl is unsubstituted or substituted with a protecting group for an amino group, and n is an integer from 0 to 3], a compound represented thereby, or a pharmaceutically acceptable salt thereof is provided.

[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 detailed in the following general production methods and examples. The compound of formula (10) of the present invention is the same as the compound of formula (1) except that it is different from the compound of formula (1) in the definition of R 10 . Therefore, the definitions, explanations, preferred embodiments, etc. for each group in the above formula (1) are all applicable to each group in formula (10) except for those regarding R 5 .

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

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

[0212] <11. General production method> Hereinafter, representative production methods of the compounds of the present invention or pharmaceutically acceptable salts thereof will be described. The compounds of the present invention can be produced by various production methods. The production methods shown below, as well as the reference examples and examples described later, are examples, and the present invention should not be construed as being limited thereto. Each starting compound may form a salt as long as it does not inhibit the reaction, and examples of such salts include the same salts as the pharmaceutically acceptable salts of the compounds described above. When not specifying a specific production method, the starting compound can be easily obtained as a commercial product and used, or can be produced according to a method known per se or a method analogous thereto. Also, the production intermediates generated in the following production methods may be isolated and purified by methods such as column chromatography (including normal phase and reverse phase) using silica gel, alumina, etc., recrystallization, reprecipitation, distillation, etc., or can be directly used in the next reaction without isolation and purification. In this specification, the content of all patent documents, non-patent documents, or reference documents explicitly cited can all be cited here as part of this specification. Compounds, their pharmaceutically acceptable salts, and their production intermediates can be produced by applying various known production methods by utilizing the characteristics based on their basic skeletons or the types of substituents. Known methods include, for example, the methods described in "ORGANIC FUNCTIONAL GROUP PREPARATIONS", 2nd Edition, ACADEMIC PRESS, INC., 1989, "Comprehensive Organic Transformations", 2nd Edition, VCH Publishers Inc., 1999, etc. In that case, depending on the type of functional group present in the compound, it may be effective in production technology to protect the functional group with an appropriate protecting group at the stage of the starting material or intermediate, or to replace it with a group that can be easily converted into the functional group. Examples of such functional groups include an amino group, a hydroxy group, a formyl group, a carbonyl group, a carboxy group, etc., and examples of their protecting groups include the protecting groups described in "Protective Groups in Organic Synthesis", 5th Edition, Wiley, 2014 by P. G. Wuts. The protecting group, or the group that can be easily converted into the functional group, may be appropriately selected and used according to the respective reaction conditions of the production method for producing the compound. According to such a method, after introducing the group and carrying out the reaction, the desired compound can be obtained by removing the protecting group or converting it into the desired group as necessary. The prodrug of the compound can be produced by introducing a specific group at the stage of the raw material or intermediate, or by performing a reaction using the obtained compound, in the same manner as the above protecting group. The reaction for producing the prodrug can be carried out by applying known methods such as ordinary esterification, amidation, dehydration, hydrogenation, etc. known to those skilled in the art. Regarding the functional group conversion and the use of protecting groups in the production intermediates used in each step of the following methods, they can be carried out by known methods or methods analogous thereto, or by the methods described in the examples below or methods analogous thereto. In the description of the following general production methods, symbols used without definition in the formula have the same meaning as above.

[0213] Hereinafter, a general production method of the compound of formula (1) of the present invention will be described. 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-Di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1’-biphenyl)-2-(2’-amino-1,1’-biphenyl)]palladium(II) methanesulfonate methanesulfonate (CAS registration 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 is a C 1-6 alkyl group which may be substituted with 1 to 3 halogen atoms, or a C 3-6 cycloalkylmethyl group which may be substituted with 1 trifluoromethyl group. Compound a12, R 4 is a C 1-6 alkylcarbonyl group which may be substituted with 1 to 3 halogen atoms. Compound a11, and R 4 is a 6-membered heteroaryl group having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl group may be substituted with 1 halogen atom). Compound a14 can be produced according to the following method. The general production methods for each reaction site are shown in order, but each step does not necessarily have to be carried out in the order shown below as long as it does not affect the reaction substrate and the reaction product.

[0215] [Chemical formula]

[0216] [In the formula, Pg 1 is a protecting group for a carboxy group (for example, a methyl group, an ethyl group, a benzyl group, or a tert-butyl group, etc.), M is a metal or a metal halide (for example, magnesium halide, lithium, or zinc halide, etc.), R a1 is a C 1-6 alkyl group which may be substituted with 1 to 3 halogen atoms, or a C 3-6 cycloalkyl group, R a2 is a substituent represented by the following formula:

[0217] [Chemical formula]

[0218] and R X is R 5 or a group convertible to R 5 and R a3 is a 6-membered heteroaryl group having 1 or 2 nitrogen atoms as ring member atoms (the heteroaryl group may be substituted with 1 halogen atom).

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

[0220] The second step 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 and 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 reaction and decarboxylation reaction in this step can be carried out, for example, by reacting compound a5 with a base such as sodium hydroxide in a solvent such as ethylene glycol under heating.

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

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

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

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

[0226] The eighth step is to obtain compound a14 from compound a9 and compound a13 through a backward amination reaction or an aromatic nucleophilic substitution reaction. The backward amination reaction in this step can be carried out, for example, by reacting compound a13 with compound a9 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. In addition, the aromatic nucleophilic substitution reaction in this step can be carried out, for example, by reacting compound a13 with compound a9 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 a group represented by the following formula:

[0228]

Chem.

[0229] in the case of the group represented by, the R 5 site can be introduced according to known methods. Literature examples of such known methods include, but are not limited to, WO 2013088315 A1, WO 2020192588 A1, etc.

[0230] R 5 is a group represented by the following formula:

[0231]

Chem.

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

[0233] R 5 is a group represented by the following formula:

[0234] [Chemical formula]

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

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

[0237] [Chemical formula]

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

[0239] The first step is a step of obtaining compound b2 from compound b1 by a deprotection reaction of the protecting group Pg 1 of the carboxy group. The deprotection reaction in this reaction can be carried out by a method usually used for deprotection of a protecting group of a carboxy group. For example, when Pg 1 is a methyl group or an ethyl group, it can be carried out by reacting compound b1 with a base such as an aqueous sodium hydroxide solution in a solvent such as methanol.

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

[0241] [Chemical formula]

[0242] [In the formula, R c1 is a single bond or a C 1-6 alkylene group which may have a substituent selected from the group consisting of a carboxy group, a hydroxy group and a C 1-6 alkoxy group, Pg 1 is a protecting group for a carboxy group, 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 obtaining compound c2 by reducing the ester of compound c1. The reduction reaction in this step can be carried out, for example, by reacting a reducing agent such as lithium aluminum hydride or diisobutylaluminum hydride with compound c1 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 para-toluenesulfonyloxy group, and they 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 a nucleophilic substitution reaction. The nucleophilic substitution reaction in this step can be carried out by reacting compound c4 with compound c3 under heating in a solvent such as DMF or acetonitrile, and / or in the presence of a base such as N,N-diisopropylethylamine.

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

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

[0248] [Chemical formula]

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

[0250] [Chemical formula]

[0251] is a group represented by the formula, or a group convertible to the group, R d2 is a C 1-3 alkylamino group, a di-C 1-3 alkylamino group, or a 4- to 6-membered saturated heterocyclic group having one nitrogen atom as a ring member atom, R d3 is a C 1-6 alkyl group which may be substituted with 1 to 3 halogen atoms.]

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

[0253] The second step is the step of obtaining compound d3 from compound d2 through 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 the step of obtaining compound d5 from compound d3 and amine d4 through a backward amination reaction. The backward amination reaction in this step can be carried out by reacting compound d3 and amine d4 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) under heating.

[0255] The fourth step is the step of obtaining compound d7 through an alkylation reaction between compound d2 and alkylating agent d6. The alkylation reaction in this step can be carried out, for example, by reacting alkylating agent d6 and compound d2 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.

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

[0257] [Chemical formula]

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

[0259] [ka]

[0260] is a group represented by 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 step of obtaining compound e4 by a coupling reaction between compound e2 and compound e3. 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). Examples of literature on the coupling reaction in this step include, for example, Catalysts, 2019, 9(1), 53.

[0263] Next, equation (3):

[0264] [ka]

[0265] [In the formula, R X is R 5 , or R 5a group convertible thereto] Disclosed is a method for producing a starting compound represented by .

[0266] (F method) Among the starting compounds (3), compounds f3 in which L 1 is an oxygen atom, compounds f6 in which L 1 is a single bond, and compounds f12 and f13 in which Q 1 is a 7-azaspiro[3.5]nonane ring can be produced according to the following method.

[0267] [Chemical formula]

[0268] [In the formula, R f1a , R f1b , R f1c , and R f1d are each independently a hydrogen atom, a halogen atom, or a C 1-6 alkyl group, R f2 is OH or a leaving group. Here, when R f2 is OH, R f3 is OH or a leaving group, or when R f2 is a leaving group, R f3 is OH, Y 1 is a halogen atom, a trifluoromethanesulfonyloxy group, a pinacolato boryl group, or a dihydroxyboryl group. Here, when Y 1 is a halogen atom or a trifluoromethanesulfonyloxy group, Y 2 is a pinacolato boryl group or a dihydroxyboryl group, or when Y 1 is a pinacolato boryl 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 thereto.]

[0269] The first step is a step of obtaining compound f3 from compound f1 and compound f2. R f2 is OH, and R f3 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 a diester of azodicarboxylic acid such as diisopropyl azodicarboxylate in a solvent such as THF. Also, when R f2 or R f3 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 heating compound f1 and compound f2 with a base such as potassium carbonate or cesium carbonate 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 of 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 water-containing 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 compound f9 and compound f10 by a Mitsunobu reaction of compound f7 and compound f8. The Mitsunobu reaction in this step can be carried out, for example, by heating compound f7 and compound f8 with a phosphorane reagent such as cyanomethylenetributylphosphorane in a solvent such as toluene.

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

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

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

[0275] Hereinafter, a general production method of the compound of formula (2) of the present invention will be described.

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

[0277] [Chemical formula]

[0278] [In the formula, R 6’ is any group selected from the groups represented by the following formula:

[0279] [Chemical formula]

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

[0281] [Chemical formula]

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

[0283] R 6’ is a group represented by the following formula:

[0284]

Chemical formula

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

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

[0287] R 6’ is a group represented by the following formula:

[0288]

Chemical formula

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

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

[0291] R 6’ When it is a group represented by the following formula:

[0292]

Chemical formula

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

[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 carbon in a solvent such as ethyl acetate or ethanol under a hydrogen atmosphere.

[0295] Next, the production method of the raw material compound represented by formula (4):

[0296]

Chemical formula

[0297] is shown.

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

[0299]

Chemical formula

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

[0301] The first step is a step of converting compound h1 into compound h2 by a carbonylation reaction. The carbonylation reaction in this step can be carried out, for example, 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, by reacting compound h1 with 2,4,6-trichlorophenyl formate (CAS registration number: 4525-65-9) under heating 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, in a solvent such as acetonitrile, in the presence of a base such as DIPEA and a catalyst such as 4-dimethylaminopyridine, by reacting compound h2 and compound h3 under heating.

[0303] (Method I) Among the starting compounds (4), compound i4 in which L 4 is -CH 2 - can be produced according to the following method.

[0304] [Chemical formula]

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

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

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

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

[0309]

Chemical formula

[0310] [In the formula, R 1 , R 2 , R 3 , R 4 , R 6’ , ring Q 1 , ring Q 2 , ring Q 3 , L 1 , and L 4 have the same meaning as described above, and L 3 is a piperazinediyl group, a piperazine-2-one diyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediy 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. Further, the condensation reaction in this step can also be carried out by reacting the acid chloride obtained 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 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 CONH (n represents an integer from 1 to 3), and the compound can be obtained under the same conditions by changing compound j1 and compound j2 to the corresponding carboxylic acid and amine, respectively.

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

[0314] (K method) Among the starting compounds (4), L 2 is -CH 2Compound k3 can be produced according to the following method.

[0315]

Chemical formula

[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 have the same meanings as described above, and L 3 is a piperazinediyl group, a piperazine-2-one diyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonane diyl group.]

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

[0318] L 2 being a C 2-6 alkylene group can also be obtained under the same conditions by changing compound k1 to the corresponding aldehyde.

[0319] (Method L) Among the starting compounds (4), compound l6 in which Q 2 is a benzene ring which may be substituted by one halogen atom and L 2 is -NHCO- can be produced according to the following method.

[0320]

Chemical formula

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

[0322]

Chemical formula

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

[0324]

Chemical formula

[0325] or a group convertible to the group.]

[0326] The first step is a step of obtaining compound l3 from compound l1 and compound l2 by a backward amination reaction. The amination reaction in this step can be carried out, for example, by reacting compound l1 and 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 a step of converting compound l3 to compound l4 by a deprotection reaction of the protecting group Pg 2 of the amino group. The deprotection reaction in this step can be carried out by a method usually used for deprotection of a protecting group for an amino group. For example, Pg2 When it is a tert-butoxycarbonyl group, it can be carried out by reacting compound l3 with an acid such as hydrochloric acid in a solvent such as dichloromethane.

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

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

[0330] Next, formula (5):

[0331]

Chemical formula

[0332] [In the formula, R X is a group convertible to a group represented by the following formula:

[0333]

Chemical formula

[0334] [wherein, n represents an integer from 1 to 3), or NHCO.] shows a method for producing a starting compound represented by

[0335] Among the starting compounds (5), L 2 is C=O, CONH, (CH 2 ) n CONH (n represents an integer from 1 to 3), or NHCO, the compound can be produced according to the same method as the J method. Among the starting compounds (5), L 2is C 1-6 The compound having an alkylene group can be produced according to the same method as the K method.

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

[0337] [Chemical formula]

[0338] [In the formula, L 3 is a piperazinediyl group, a piperazine-2-onediyl group, a piperidinediyl group, a pyrrolidinediyl group, an azetidinediyl group, or a 3-oxa-9-azabicyclo[3.3.1]nonanediy group, Lg is a leaving group (for example, 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] [Chemical formula]

[0340] (In the formula, n is an integer from 0 to 5) and is a group represented by Pg 1 is a protecting group for a carboxy group, R X is a group convertible to the following formula:

[0341] [Chemical formula]

[0342] and is a group represented by.]

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

[0344] The second step is to convert the 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, a trifluoromethanesulfonyloxy group, etc. The conversion into the leaving group can be carried out by a commonly used method (reagents, solvents, reaction conditions, etc.).

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

[0346] Next, formula (6):

[0347]

Chemical formula

[0348] [wherein, R y is a group convertible to a group represented by the following formula:

[0349]

Chemical formula

[0350] [Formula ends] shows a method for producing a starting compound represented by the formula.

[0351] The starting material compound (6) is either known or is prepared from a known compound as a starting material according to a known method or a method similar thereto. The known compound can be purchased from a commercial supplier or can be easily synthesized by a method described in the literature or a method 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] Examples of the production method of the starting material compound (6) are described below from Method N to Method P, but the synthesis method of the starting material compound (6) is not limited thereto.

[0353] (Method N) Among the starting material compounds (6), Q 3 is any group selected from the following formula:

[0354] [Chemical formula]

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

[0356] [Chemical formula]

[0357] [In the formula, Y 1 is a halogen atom, Y 2 is a halogen atom, a dihydroxyboryl group, a pinacolato boryl group, or the like, R n1a and R n1b are each independently a hydrogen atom or a halogen atom, Pg 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 into compound n2 by a halogenation reaction. The halogenation reaction in this step can be carried out, for example, by reacting compound n1 with a halogenating agent such as N-bromosuccinimide, benzyltrimethylammonium tribromide, N-iodosuccinimide, etc. in a solvent such as DMF.

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

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

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

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

[0363] (O method) Among the starting compounds (6), compound o4 in which Q 3 is any group selected from the following formula:

[0364]

Chemical formula

[0365] can be produced according to the following method.

[0366]

Chemical formula

[0367] [In the formula, A 1 , A 2 , and A 3 are each independently a carbon atom or a nitrogen atom, X o is a halogen atom, a pinacolato boryl group, or the like, Y 1 is a nitro group or a halogen atom, R o1 is R 8 , or R 6’ , R o4 is R 8 , or R 6’ , A 1 When is a nitrogen atom, R o2 does not exist, A 1 When is a carbon atom, R o2 is a hydrogen atom or a halogen atom, or R o1 and R o2are combined with each other to form the following formula:

[0368] [Chemical formula]

[0369] (wherein the lower end of the partial structure is a bond of R o2 and the upper end of the partial structure is a bond of R o1 ) and may form any partial structure selected from the group represented by A 2 When is a nitrogen atom, R o3 does not exist, A 2 When is a carbon atom, R o3 is a hydrogen atom or a halogen atom, A 3 When is a nitrogen atom, R o4 does not exist, A 3 When 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 compounds as starting materials with known methods or methods similar thereto. Examples of literature of the above-known methods include, for example, Bioorg. Med. Chem., 2013, 21, 125, J. Med. Chem., 1995, 38, 5, 771 - 793, WO2011163355 A1, WO2005044793 A2, WO2007015877 A2, WO2021213929 A1, WO2018039384 A1, WO2016097749 A1, etc., but are not limited thereto.

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

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

[0373] (P method) Among the starting compounds (6), Q 3 is any group selected from the following formula:

[0374] [Chemical formula]

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

[0376] [Chemical formula]

[0377] [In the formula, A 1 is CH or a nitrogen atom, A 2 is CH 2 or NH, X p is a halogen atom, R p1 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 diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate in a solvent such as dichloroethane in the presence of an acid such as boric acid or p-toluenesulfonic acid under heating.

[0379] The second step is to obtain compound p4 by ureation from compound p2 and compound p3. The ureation reaction in this step can be carried out under the same conditions as the fourth step of the L method.

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

[0381] Next, formula (7):

[0382]

Chemical formula

[0383] [wherein, R x’ is a group convertible to a group represented by the following formula:

[0384]

Chemical formula

[0385] represents a method for producing a starting material compound.

[0386] (Q method) Among the starting material compounds (7), R 4 is an optionally substituted C 1-6 alkyl group with 1 to 3 halogen atoms, or an optionally substituted C 3-6 cycloalkylmethyl group with 1 trifluoromethyl group, and compound q12, R 4which may be substituted with 1 to 3 halogen atoms, C 1-6 Compound q11 which is an alkylcarbonyl group, and R 4 Compound q14, wherein R is a 6-membered heteroaryl group having 1 or 2 nitrogen atoms as ring members (the heteroaryl group may be substituted with 1 halogen atom), can be produced according to the following method. The general production methods for each reaction site are shown in order, but each step does not necessarily have to be carried out in the order shown below as long as it does not affect the reaction substrate and the reaction product.

[0387] [Chemical formula]

[0388] [wherein, Pg 1 is a protecting group for a carboxy group, M is a metal or a metal halide (for example, magnesium halide, lithium, zinc halide, etc.), R q1 is a hydrogen atom, a C 1-5 alkyl group which may be substituted with 1 to 3 halogen atoms, or a C 3-6 cycloalkyl group which may be substituted with 1 trifluoromethyl group, R q2 is a group represented by the following formula:

[0389] [Chemical formula]

[0390] and R q3 is a 6-membered heteroaryl group having 1 or 2 nitrogen atoms as ring members (the heteroaryl group may be substituted with 1 halogen atom).]

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

[0392] The second step is to obtain compound q5 by subjecting compound q4 to 1,4-nucleophilic addition to the α,β-unsaturated ester of compound q3. The 1,4-nucleophilic addition reaction in this step can be carried out, for example, by reacting compound q3 and compound q4 in a solvent such as THF 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 to obtain compound q6 by hydrolysis of the ester group of compound q5 and decarboxylation of the resulting carboxy group. The hydrolysis reaction and decarboxylation reaction in this step can be carried out, for example, by reacting compound q5 with a base such as sodium hydroxide in a solvent such as ethylene glycol under heating.

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

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

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

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

[0398] The eighth step is the step of obtaining compound q14 from compound q9 and compound q13 by a backward amination reaction or an aromatic nucleophilic substitution reaction. The backward amination reaction 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. Also, the aromatic nucleophilic substitution reaction 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] (R method) Among the compounds represented by formula (7), compound r4 in which L 1 is -C(=O)- can be produced according to the following method.

[0400] [Chemical formula]

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

[0402] [Chemical formula]

[0403] and M is a dihydroxyboronyl group, a pinacolato boronyl group, etc.]

[0404] The first step is to convert carboxylic acid r1 into 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 to obtain compound r4 by the coupling reaction of compound r2 and compound r3. 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). For this step, as a literature example, Catalysts 2019, 9(1), 53 can be cited.

[0406] (S method) In the compound represented by formula (7), R 1 site can be produced according to the following production method.

[0407] [Chemical formula]

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

[0409] [Chemical formula]

[0410] or a group convertible to the group represented by the formula, R b is C 1-3 alkylamino group, diC 1-3an alkylamino group or a 4- to 6-membered saturated heterocyclic group having one nitrogen atom as a ring member atom, R c is a C 1-6 alkyl group which may be substituted with 1 to 3 halogen atoms.]

[0411] The first step is a step of obtaining compound s2 from compound s1 by a deprotection reaction of a protecting group Pg 3 of a hydroxy group. The deprotection reaction in this step can be carried out by a method usually used for deprotection of a protecting group of a hydroxy group. For example, when Pg 3 is a methyl group, it 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 from 80°C to 160°C.

[0412] The second step is a step of obtaining compound s3 by triflation of the hydroxy group of compound s2. The triflation 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 a backward amination reaction. The backward amination reaction 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 to obtain compound s7 from compound s2 through an alkylation reaction using alkylating agent s6. The alkylation reaction in this step can be carried out, for example, by reacting compound s2 with alkylating agent s6 such as alkyl halide in a solvent like 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, formula (8):

[0416]

Chemical formula

[0417] [In the formula, R y’ is a group convertible to a group represented by the following formula:

[0418]

Chemical formula

[0419] . The manufacturing method of the raw material compound represented by this is shown.

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

[0421]

Chemical formula

[0422] As represented by, for the compound where L 4 is -C(=O)-, it can be manufactured by the same method as the H method.

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

[0424]

Chemical formula

[0425] As represented by, for L 4is CH 2 The compound can be produced by the same method as in Method I.

[0426] (Method T) Among the starting compounds (8), the compound t6 in which L 4 is NH, and the compound t8 in which L 4 is N-R 9 (R 9 represents a C 1-6 alkyl group) can be produced according to the following method.

[0427] [Chemical formula]

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

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

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

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

[0432] The fourth step is to obtain compound t6 from compound t2 and compound t5 through a reductive amination reaction. The reductive amination reaction in this step can be carried out under the same conditions as the second step of Method I. Also, 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 to obtain compound t8 from compound t6 and compound t7 through a reductive amination reaction. The reductive amination reaction in this step can be carried out under the same conditions as the fourth step of this method.

[0434] Next, the manufacturing method of the starting compound represented by formula (9):

[0435]

Chemical formula

[0436] is shown.

[0437] (Method U) Among the starting compounds (9), compound u3 in which L 1 is an oxygen atom, compound u6 in which L 1 is a single bond, and compounds u12 and u13 in which Q 1 is a 7-azaspiro[3.5]nonane ring can be manufactured according to the following methods respectively.

[0438]

Chemical formula

[0439] [In the formula, R u1a , R u1b , R u1c , and R u1d are each independently a hydrogen atom, a halogen atom, or a C 1-6 alkyl group, R u2 is a hydroxy group or a leaving group (here, Ru2 When R is a hydroxy group, u3 R is a hydroxy group or a leaving group, or when u2 R is a leaving group, u3 R is a hydroxy group), Y 1 is a halogen atom, a trifluoromethanesulfonyloxy group, a pinacolato boryl group, or a dihydroxyboryl group (where when 1 Y is a halogen atom or a trifluoromethanesulfonyloxy group, 2 Y is a pinacolato boryl group or a dihydroxyboryl group, or when 1 Y is a pinacolato boryl group or a dihydroxyboryl group, 2 Y is a halogen atom or a trifluoromethanesulfonyloxy group), R x’ is a group convertible to a group represented by the following formula:

[0440]

Chemical formula

[0441] and Pg 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. When u2 R is a hydroxy group and u3 R is a hydroxy group, this reaction can be carried out by 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 a diester of azodicarboxylic acid such as diisopropyl azodicarboxylate in a solvent such as tetrahydrofuran. Also, u2 or R u3When any of them 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 water-containing 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 compound u9 and compound u10 from compound u7 and compound u8 by Mitsunobu reaction. The Mitsunobu reaction in this step can be carried out, for example, by reacting compound u7 and compound u8 with a phosphoran reagent such as cyanomethylenetributylphosphorane under heating in a solvent such as toluene.

[0445] The fourth step is a step of obtaining compound u11 by a reduction reaction of compound u9. The reduction reaction in this step can be carried out under the same conditions as the first step of Method M.

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

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

[0448] <12. Activity> In one aspect of the present invention, the compound or multifunctional molecule according to the present invention specifically binds to SF-1. The binding activity to SF-1 can be measured using any known method. For example, by reacting a test substance, a molecule known to specifically bind to SF-1 (especially the SF-1 ligand binding domain (LBD)), and SF-1 (especially SF-1-LBD), and quantifying the decrease in the binding rate of SF-1 by a molecule known to specifically bind to SF-1 (for example, calculating the IC 50 value), it can be measured. Generally, in such a test system, a test substance with an IC 50 value of 100 μM or less is considered to specifically bind to SF-1. Therefore, in one aspect of the present invention, the compound or multifunctional molecule according to the present invention has an IC 50 value of 100 μM or less, preferably an IC 50 value of 10 μM or less, and particularly preferably an IC 50 value of 1 μM or less with respect to the decrease in the binding rate of SF-1 by a molecule known to specifically bind to SF-1 (for example, the DAX1 peptide). In another aspect of the present invention, the compound or multifunctional molecule according to the present invention has an IC 50 value of 100 μM or less, preferably an IC 50 value of 10 μM or less, and particularly preferably an IC 50 value of 1 μM or less with respect to the decrease in the binding rate of SF-1-LBD by the DAX1 peptide under the test system and test conditions disclosed in Test Example 1 herein.

[0449] In one aspect of the present invention, the compound or multifunctional molecule according to the present invention has SF-1 antagonist activity. The SF-1 antagonist activity can be measured using any known method. For example, by adding a test substance to cells expressing SF-1, culturing for a certain period, and then quantifying the decrease in the expression level of a target gene of SF-1 (for example, CYP11A1, CYP17A1, CYP21A2, STAR, etc.) (for example, calculating the IC 50By calculating the value, it can be measured. Generally, in such a test system, a test substance with an IC 50 value of 100 μM or less for the target gene of SF-1 is considered to have antagonist activity against SF-1. Therefore, in one aspect of the present invention, the compound or multifunctional molecule according to the present invention has an IC 50 value of 100 μM or less, preferably an IC 50 value of 10 μM or less, and particularly preferably an IC 50 value of 1 μM or less, against the target gene of SF-1 (for example, CYP11A1, CYP17A1, CYP21A2, and / or STAR). In another aspect of the present invention, the compound or multifunctional molecule according to the present invention has an IC 50 value of 100 μM or less, preferably an IC 50 value of 10 μM or less, and particularly preferably an IC 50 value of 1 μM or less, against CYP11A1, CYP17A1, CYP21A2, and / or STAR under the test system and test conditions disclosed in Test Example 2 herein.

[0450] In one aspect of the present invention, the compound or multifunctional molecule according to the present invention has SF-1 degradation-inducing activity. The SF-1 degradation-inducing activity can be measured using any known method. For example, it can be measured by adding a test substance to cells expressing SF-1, culturing for a certain period, and then quantifying the expression level of SF-1. The SF-1 degradation-inducing activity can also be measured, for example, by knocking in a peptide tag (for example, HiBiT tag) that is easy to detect at the endogenous SF-1 locus in cells expressing SF-1, adding a test substance to the cells, culturing for a certain period, and then observing the expression level of the peptide tag. Generally, in such a test system, a test substance with a concentration (DC 50 value) that induces 50% degradation of SF-1 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 multifunctional molecule according to the present invention has a DC 50 value of 100 μM or less, preferably a DC50 value, particularly preferably a DC value of 1 μM or less 50 value. In another aspect of the present invention, the compound or multifunctional molecule according to the present invention has a DC value of 100 μM or less, preferably a DC value of 10 μM or less, particularly preferably a DC value of 1 μM or less, for SF-1 under the test systems and test conditions disclosed in Test Example 3 herein. 50 value, preferably a DC value of 10 μM or less 50 value, particularly preferably a DC value of 1 μM or less 50 value.

[0451] In one aspect of the present invention, the compound or multifunctional molecule according to the present invention has growth inhibitory activity against tumors in which SF-1 is involved in their development and progression. In another aspect of the present invention, the compound or multifunctional molecule according to the present invention has growth inhibitory activity against adrenocortical cancer. In yet another aspect of the present invention, the compound or multifunctional molecule according to the present invention has growth inhibitory activity against NCI-H295R cells, an adrenocortical cancer cell line. The growth inhibitory activity of tumor cells can be measured using any known method. Typically, a test substance is added to model cells of the target tumor, cultured for a certain period, and then the growth rate of the tumor cells is quantified. Generally, in such test systems, a test substance with a concentration (GI value) that inhibits the growth of tumor cells by 50% of 100 μM or less is considered to have growth inhibitory activity. Therefore, in one aspect of the present invention, the compound or multifunctional molecule according to the present invention has a GI value of 100 μM or less, preferably a GI value of 10 μM or less, particularly preferably a GI value of 1 μM or less, for tumor cells (e.g., NCI-H295R cells). In another aspect of the present invention, the compound or multifunctional molecule according to the present invention has a GI value of 100 μM or less, preferably a GI value of 10 μM or less, particularly preferably a GI value of 1 μM or less, for tumor cells (e.g., NCI-H295R cells) under the test systems and test conditions disclosed in Test Example 4 herein. 50 value) of 100 μM or less is considered to have growth inhibitory activity. Therefore, in one aspect of the present invention, the compound or multifunctional molecule according to the present invention has a GI value of 100 μM or less, preferably a GI value of 10 μM or less, particularly preferably a GI value of 1 μM or less, for tumor cells (e.g., NCI-H295R cells). 50 value, preferably a GI value of 10 μM or less 50 value, particularly preferably a GI value of 1 μM or less 50 value. In another aspect of the present invention, the compound or multifunctional molecule according to the present invention has a GI value of 100 μM or less, preferably a GI value of 10 μM or less, particularly preferably a GI value of 1 μM or less, for tumor cells (e.g., NCI-H295R cells) under the test systems and test conditions disclosed in Test Example 4 herein. 50 value, preferably a GI value of 10 μM or less 50 value, particularly preferably a GI value of 1 μM or less 50 value.

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

Example

[0453] The present invention will be described in detail by the following examples, but these are merely examples and do not limit the present invention, and may be changed without departing from the scope of the present invention. In the following examples, “%” indicates mol / mol% for the yield, volume% for the solvent used in chromatography, and weight% for others. The nuclear magnetic resonance spectrum (hereinafter 1 1H-NMR, resonance frequency 400 MHz or 500 MHz) describes the chemical shift value as a δ value (ppm) using tetramethylsilane as a standard substance or using the chemical shift value of the deuterated solvent used as a reference value. Other abbreviations used in the text indicate 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 CDCl 3 : deuterated chloroform DMSO-d 6 : deuterated dimethyl sulfoxide CD 3 OD: deuterated methanol 1H-NMR: proton nuclear magnetic resonance HPLC: high performance liquid chromatography SFC: supercritical fluid chromatography sCO 2 : supercritical carbon dioxide APCI: atmospheric pressure chemical ionization method ESI: electrospray ionization method 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 Registry Number: 161265-03-8) IPA: Isopropyl alcohol DCM: Dichloromethane DMSO: Dimethyl sulfoxide TLC: Thin layer chromatography

[0454] In addition, in the following examples, the formula:

[0455]

Chemical formula

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

[0457] The reagents, solvents, apparatuses, etc. used in the following examples are commercially available unless otherwise specified. In addition, the starting compounds are known compounds unless otherwise specified, and those synthesized and identified according to known methods or methods analogous thereto were used if they were commercially available.

[0458] <Example A1> Ethyl cyano(2,2-dimethyltetrahydro-4H-pyran-4-ylidene)acetate Ethyl cyanoacetate (175 mL, 1.65 mol) was added dropwise to 2,2-dimethyltetrahydro-4H-pyran-4-one (CAS registration number: 1194-16-7) (200 g, 1.56 mol) over 10 minutes under ice-cooling, acetic acid (18 mL, 0.32 mol) was added dropwise over 5 minutes, and then 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, filtered, and 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 Using the compound obtained in <Example A1> and 4-chlorophenylmagnesium bromide (CAS Registry Number: 873-77-8), the title compound was obtained in the same manner as in <Example C3>.

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

[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, and the mixture was stirred at room temperature for 1 hour and at 95 °C for 3 hours. The reaction solution 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, filtered, and 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 obtain 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 Using the compounds obtained in <Example A4> and <Example A3>, the title compound was obtained in the same manner as in <Example D1>.

[0463] <Example A6> trans-4-(4-{[{2-[4-(4-chlorophenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(2,2-dimethylpropanoyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example A5>, the title compound was obtained by performing the same operations as in <Example D2> and <Example S4> in sequence.

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

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

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

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

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

[0469] <Example C1> Ethyl (cis-4-hydroxycyclohexyl)acetate To a solution of cis-2-(4-hydroxycyclohexyl)acetic acid (CAS Registry Number: 68592-22-3) (2.53 g, 16.0 mmol) in ethanol (46 mL) was added sulfuric acid (0.086 mL, 1.60 mmol), and the mixture was heated to reflux for 7 hours. The reaction solution was returned to room temperature, 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, filtered, and the filtrate was concentrated under reduced pressure to obtain the title compound (2.66 g, 14.3 mmol, yield 89%).

[0470] <Example C2> Ethyl [trans-4-(2-chloro-4-formylphenoxy)cyclohexyl]acetate Using the compound obtained in <Example C1> and 3-chloro-4-hydroxybenzaldehyde (CAS Registry Number: 2420-16-8), the title compound was obtained in the same manner as in <Example A4>.

[0471] <Example C3> Ethyl cyano[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]acetate To a solution of ethyl cyano(2,2-dimethyltetrahydro-4H-pyran-4-ylidene)acetate (8.92 g, 40.0 mmol) in THF (131 mL) was added copper(I) bromide dimethyl sulfide complex (0.805 g, 3.92 mmol) at -78 °C, and the mixture was stirred at the same temperature for 2 hours. Then, 4-methoxyphenylmagnesium bromide (CAS Registry Number: 13139-86-1) (0.50 mol / L THF solution, 100 mL, 50 mmol) was added dropwise over 20 minutes at the same temperature. The reaction mixture was stirred for 1.5 hours while warming to room temperature and left overnight at room temperature. Copper(I) bromide dimethyl sulfide complex (0.805 g, 3.92 mmol) was added to the reaction mixture at -78 °C, and the mixture was stirred at the same temperature for 5 minutes. Then, 4-methoxyphenylmagnesium bromide (0.50 mol / L THF solution, 47 mL, 23.5 mmol) was added dropwise over 5 minutes at the same temperature, and the mixture was stirred for 6 hours while 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 obtained organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 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. 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. Then the mixture was extracted with DCM. The obtained 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 obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (5.91 g, 22.8 mmol, yield 70%).

[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) was added lithium aluminum hydride (3.19 g, 84.1 mmol) over 10 minutes under ice-cooling. The mixture was stirred at room temperature while warming to 35 °C over 1.5 hours, at 35 °C for 4 hours, and at 50 °C for 2 hours. After cooling, water (3.2 mL) was added to the reaction mixture under ice-cooling, followed by 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 obtained residue was purified by amine-modified silica gel column chromatography (hexane / ethyl acetate and ethyl acetate / methanol) to give 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 Using the compounds obtained in <Example C2> and <Example C5>, the title compound was obtained in the same manner as in <Example D1>.

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

[0476] <Example C8> [trans-4-(2-chloro-4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexyl]acetic acid Using the compound obtained in <Example C7>, the 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 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) was added with ethyl trans-4-(4-formylphenoxy)cyclohexanecarboxylate (4.00 g, 14.5 mmol) at room temperature, and the mixture was heated to reflux with a Dean-Stark apparatus attached. The mixture was stirred for 7 hours while gradually removing the solvent, and then left standing overnight at room temperature. The reaction solution was heated to reflux with a Dean-Stark apparatus attached. The mixture was stirred for 1 hour while gradually removing the solvent, and after cooling, the organic solvent was distilled off under reduced pressure. The obtained 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 for 1.5 hours while warming up to room temperature. Saturated aqueous ammonium chloride solution and water were added to the reaction solution under ice-cooling, and the mixture was left standing overnight. The reaction mixture was extracted with DCM, and the obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (DCM / methanol) to obtain the title compound (5.13 g, 9.79 mmol, yield 68%).

[0478] <Example D2> Ethyl trans-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 mixture under ice-cooling, and the mixture was extracted with DCM. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (1.19 g, 1.96 mmol, 92% yield).

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

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

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

[0482] <Example F1> trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-hydroxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid To a solution of trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)cyclohexanecarboxylic acid (200 mg, 0.345 mmol) in DMF (3.45 mL) was added sodium thiomethoxide (0.484 g, 6.90 mmol) at room temperature, and the mixture was stirred at 100 °C for 8 hours and then left at room temperature overnight. Saturated aqueous ammonium chloride solution and water were added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate and DCM. The obtained organic layer was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (DCM / methanol) to give 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 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) were added DIPEA (2.05 mL, 11.8 mmol) and iodoethane (0.940 mL, 11.8 mmol) at room temperature. The mixture was stirred at room temperature for 1 hour and then left overnight at room temperature. To the reaction mixture were added DIPEA (0.819 mL, 4.70 mmol) and iodoethane (0.376 mL, 4.70 mmol) at room temperature. The mixture was stirred at the same temperature for 10 hours and then left for 2 days at room temperature. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The obtained 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 obtained 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 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) were added potassium carbonate (146 mg, 1.06 mmol) and 2-bromopropane (0.0991 mL, 1.06 mmol) at room temperature, and the mixture was stirred at 130 °C for 4.5 hours and then left at room temperature for 4 days. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (78.7 mg, 0.124 mmol, 92% yield).

[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), pyridine (1.32 mL, 16.3 mmol) was added under ice-cooling, and then trifluoromethanesulfonic anhydride (0.333 mL, 1.98 mmol) was added little by little. The mixture was stirred at the same temperature for 30 minutes and at room temperature for 1 hour. Water was added to the reaction mixture under ice-cooling, and the mixture was extracted with a hexane / ethyl acetate mixed solvent (ratio 2 / 1). The obtained 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 obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain 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 with tris(dibenzylideneacetone)dipalladium(0) (6.3 mg, 0.0069 mmol), 2-(di-tert-butylphosphino)biphenyl (4.1 mg, 0.0138 mmol), pyrrolidine (CAS Registry Number: 123-75-1) (0.0085 mL, 0.103 mmol) and tripotassium phosphate (20.5 mg, 0.0964 mmol) at room temperature, stirred at 95 °C for 9 hours, and left at room temperature for 3 days. Water was added to the reaction mixture at room temperature, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with water, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (36.2 mg, 0.0560 mmol, yield 81%).

[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 the same manner as in <Example S4>.

[0489] <Example H1> trans-4-(4-{[(2,2-dimethylpropanoyl){2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino]methyl}phenoxy)-N-(dimethylsulfamoyl)cyclohexanecarboxamide 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 (85 mg, 0.15 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (CAS Registry Number: 25952-53-8) (56 mg, 0.29 mmol), and 4-dimethylaminopyridine (54 mg, 0.44 mmol) in DCM (2 mL) was added with N,N-dimethylsulfamide (CAS Registry Number: 3984-14-3) (36 mg, 0.29 mmol) at room temperature and stirred at room temperature for 1 day. After the reaction solution was concentrated under reduced pressure, 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, 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 (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 To a mixture of ethyl trans-4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}cyclohexanecarboxylate (60 mg, 0.11 mmol) and 1,4-dioxane (1 mL), 2-bromopyridine (CAS Registry Number: 109-04-6) (0.030 mL, 0.31 mmol), cesium carbonate (120 mg, 0.368 mmol), and RuPhos Pd G3 (4 mg, 0.005 mmol) were sequentially added, and the mixture was stirred at 100 °C for 2 h. Potassium phosphate tribasic (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 solution, and the mixture was stirred at 100 °C for 8 h. RuPhos Pd G3 (4 mg, 0.005 mmol) was added to the reaction solution, and the mixture was stirred at 100 °C for 3 h. BrettPhos Pd G3 (4 mg, 0.004 mmol) and cesium carbonate (120 mg, 0.368 mmol) were added to the reaction solution, and the mixture was stirred at 100 °C for 4 h. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained 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 Using the compound obtained in <Example I1>, the title compound was obtained in the same manner as in <Example S4>.

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

[0493] <Example J2> Methyl 3-(4-{4-[({2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}amino)methyl]phenoxy}phenyl)-2,2-dimethylpropanoate 2-[4-(4-Methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]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, and then the mixture was extracted with DCM. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain 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 at room temperature for 3 days under a nitrogen atmosphere. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (247 mg, 0.384 mmol, 89% yield).

[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) was added rhodium-alumina (10.0 g), and the mixture was stirred at 50 °C for 8 hours under a hydrogen atmosphere. The insoluble material was filtered off through celite and washed with ethanol. The resulting solution was concentrated to about 200 mL, rhodium-alumina (10.0 g) was added, and the mixture was stirred at 50 °C for 4 hours under a hydrogen atmosphere. The insoluble material 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. Under water cooling, benzyl bromide (11.7 mL, 98.6 mmol) was added dropwise, 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 obtain the title compound (7.65 g, 30.8 mmol, yield 47%).

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

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

[0499] <Example K4> Benzyl [trans-4-(4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoropropyl)amino]methyl}phenoxy)cyclohexyl]acetate Using the compound obtained in <Example K3> and 3,3,3-trifluoropropionaldehyde (CAS registration 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 Using the compound obtained in <Example G1> and methylamine (2.0 mol / L THF solution), the title compound was obtained in the same manner as in <Example G2>.

[0502] <Example L2> trans-4-(4-{[(2-{2,2-dimethyl-4-[4-(methylamino)phenyl]tetrahydro-2H-pyran-4-yl}ethyl)(2,2-dimethylpropanoyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid 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 The racemic 2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethanamine was optically resolved by chiral HPLC [column: CHIRALCEL OZ-H (registered trademark, Daicel Corporation), mobile phase: hexane / IPA = 60 / 40 (V / V)], and the title compound was obtained as the later eluting component. 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 To a solution of 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 HATU (43.8 g, 115 mmol), and the mixture was stirred at room temperature for 20 minutes. The reaction solution was cooled to 0 °C and stirred for 5 minutes. To the reaction solution was sequentially added dropwise 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), and the mixture was stirred at room temperature for 24 hours. The reaction solution was diluted with ethyl acetate, washed successively 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 obtain the title compound (36.2 g, 90.2 mmol, yield 94%).

[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 the mixture was stirred under reflux for 9 hours. After the reaction solution was cooled to room temperature, methanol (60 mL) was added, and the mixture was stirred under reflux for 3 hours. The reaction solution was cooled to room temperature and concentrated under reduced pressure. Ethyl acetate was added to the residue, and the mixture was 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 obtain the title compound (22.1 g, 57.0 mmol, 93% yield).

[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 Using the compounds obtained in <Example M3> and <Example A4>, the title compound was obtained in the same manner as in <Example T1>.

[0507] <Example M5> trans-4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)cyclohexanecarboxylic acid Using the compound obtained in <Example M4>, the title compound was obtained in the same manner as in <Example S4>.

[0508] <Example N1> N-[4-(4-Bromophenoxy)benzyl]-N-{2-[4-(4-Methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide Using the compound obtained in <Example C5> and 4-(4-Bromophenoxy)benzaldehyde (Bioorg. Med. Chem. Lett., 2004, 14, 4179-4183.), the title compound was obtained by performing the same operations as in <Example D1> and <Example D2> in sequence.

[0509] <Example N2> N-{4-[(4-{[Dimethyl(oxide)-λ 6 -Sulfanylidene]amino}cyclohexyl)oxy]benzyl}-N-{2-[4-(4-Methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide A solution of N-[4-(4-bromophenoxy)benzyl]-N-{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}-2,2-dimethylpropanamide (150 mg, 0.246 mmol) in toluene (5 mL) was added with dimethylsulfoximine (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), and stirred under heating under reflux for 9 hours in a nitrogen atmosphere. Dimethylsulfoximine (40 mg, 0.429 mmol), cesium carbonate (170 mg, 0.522 mmol), (S)-(-)-Tol-BINAP (28 mg, 0.041 mmol), and palladium(II) acetate (7 mg, 0.03 mmol) were added to the reaction solution, and stirred under heating under reflux for 8 hours in a nitrogen atmosphere. (S)-(-)-Tol-BINAP (27 mg, 0.040 mmol) and palladium(II) acetate (8 mg, 0.04 mmol) were further added to the reaction solution, and stirred under heating under reflux for 4 hours in a nitrogen atmosphere. After the reaction solution was filtered, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel chromatography (DCM / methanol) to obtain the title compound (7 mg, 0.01 mmol, yield 4%).

[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 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) was successively added with 2-chloro-5-fluoropyrimidine (CAS Registry Number: 62802-42-0) (0.030 mL, 0.24 mmol), 1,8-diazabicyclo[5.4.0]-7-undecene (0.040 mL, 0.27 mmol), and cesium fluoride (1 mg, 0.007 mmol), and 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 combined organic layers were 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 (47.4 mg, 0.0765 mmol, 61% yield).

[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 the same manner as 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 mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (878 mg, 3.09 mmol, 52% yield).

[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 <Example M3> Using the compounds obtained in <Example M3> and <Example P1>, the title compound was obtained in the same manner as in <Example T1>.

[0514] <Example P3> 2-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid <Example P2> 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 Using the compound obtained in <Example C5> and methyl 4-formyl-2-methylbenzoate (CAS Registry Number: 74733-23-6), the title compound was obtained in the same manner as in <Example J2>.

[0516] <Example Q2> Methyl 4-{[{2-[4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropanoyl)amino]methyl}-2-methylbenzoate 3,3,3-Trifluoro-2,2-dimethylpropanoic acid (CAS Registry Number: 889940-13-0) (1.25 g, 8.04 mmol) was dissolved in DCM (10 mL), DMF (0.05 mL) was added, and the mixture was stirred at room temperature. Oxalyl chloride (0.748 mL, 8.84 mmol) was added 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, 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 (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 thereto, and the mixture was stirred at room temperature for 1.5 hours, and then the solvent was distilled off to obtain the corresponding acid chloride (1.06 g, 1.87 mmol, yield 97%). To the obtained acid chloride (191 mg, 0.336 mmol), [4-(2-ethoxycarbonylethyl)phenyl]boronic acid (CAS registration number: 660440-57-3) (60.0 mg, 0.270 mmol), toluene (8.0 mL), cesium carbonate (225 mg, 0.692 mmol), and tetrakis(triphenylphosphine)palladium(0) (40.6 mg, 0.0351 mmol) were added, and the mixture was stirred at 80 °C for 6 hours. After the reaction solution was returned to room temperature, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate). The obtained crude purified product was dissolved in ethanol (4.0 mL), 1 mol / L aqueous sodium hydroxide solution (0.754 mL, 0.754 mmol) was added, and the mixture was stirred at room temperature for 16 hours. The reaction solution was concentrated under reduced pressure, water and 2 mol / L hydrochloric acid were added to the residue for neutralization, and then the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (15.0 mg, 0.0220 mmol, yield 15%).

[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 Using the compounds obtained in <Example M3> and <Example R1>, the title compound was obtained in the same manner as in <Example T1>.

[0521] <Example R3> (2S)-2-Ethoxy-3-[4-(4-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyltetrahydro-2H-pyran-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}phenoxy)phenyl]propanoic acid Using the compound obtained in <Example R2>, the title compound was obtained in the same manner as in <Example S4>.

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

[0523] <Example S2> Ethyl {trans-4-[(5-formylpyridin-2-yl)oxy]cyclohexyl}acetate Using the compound obtained in <Example S1> and 6-hydroxynicotinaldehyde (CAS Registry Number: 106984-91-2), the title compound was obtained in the same manner as in <Example A4>.

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

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

Claims

1. The following groups: (3RS)-3-[5-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-3-methyl-2-oxo-2,3-dihydro-1H-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]quinoxaline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, and (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione or a pharma- ceutically acceptable salt thereof.

2. (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, and (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 The compound according to claim 1, which is any one selected from the following:

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, (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, 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[4,5,1-ij]quinolin-1(2H)-yl]piperidine-2,6-dione, The compound according to claim 1, which is any one selected from the following: Claim 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, (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, and (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 The compound according to claim 1, which is any one selected from the following:

5. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, (3R)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione, and (3S)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The compound according to claim 1, which is any one selected from the following:

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 benzenesulfonate 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

7. (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 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

8. (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 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

9. (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 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

10. (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 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

11. (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-Camphorsulfonic acid salt 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

12. (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 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

13. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione monoethanesulfonate 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein: Claim 14: (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione salicylate 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

15. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione monosalicylate 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

16. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione benzenesulfonate 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

17. (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 monobenzenesulfonate 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

18. (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 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

19. (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-Camphorsulfonic acid salt 2. A pharma- ceutically acceptable salt of the compound of claim 1, wherein:

20. (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, (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, (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, (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, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione salicylate, (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione benzenesulfonate, and (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-Camphorsulfonic acid salt A crystal of any one of the compounds selected from the above.

21. (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 crystal according to claim 20, which is a crystal of the benzenesulfonate salt and 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).

22. (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 crystal according to claim 20, which is a crystal of the ethanesulfonate salt and 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).

23. (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 crystal of 10-camphorsulfonate according to claim 20, 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).

24. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The crystal according to claim 20, which is a crystal of the ethanesulfonate salt, and 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).

25. (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 21. The crystal of claim 20, wherein the crystal is a salicylate salt, and in a powder X-ray diffraction pattern obtained by irradiation with copper Kα radiation (λ=1.54 angstroms), the crystal 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.

26. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The crystal according to claim 20, which is a crystal of benzenesulfonate salt and 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).

27. (3RS)-3-[7-(4-{[(4R)-4'-{[{2-[(4R)-4-(4-methoxyphenyl)-2,2-dimethyloxan-4-yl]ethyl}(3,3,3-trifluoro-2,2-dimethylpropyl)amino]methyl}-2,3,4,5-tetrahydro[1,1'-biphenyl]-4-yl]methyl}piperazine-1-carbonyl)-2-oxo-5,6-dihydro-4H-imidazo[1,5,4-de]quinoxaline-1(2H)-yl]piperidine-2,6-dione The crystal of 10-camphorsulfonate according to claim 20, 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).

28. A composition for inhibiting Steroidogenic Factor 1, comprising the compound according to claim 1 or a pharma- ceutically acceptable salt thereof.

29. A composition for inducing degradation of Steroidogenic Factor 1, comprising the compound according to claim 1 or a pharma- ceutical acceptable salt thereof.

30. 10. A pharmaceutical composition comprising the compound of claim 1 or a pharma- ceutically acceptable salt thereof.

31. A pharmaceutical composition comprising the compound of claim 2 or a pharma- ceutically acceptable salt thereof.

32. A pharmaceutical composition comprising the compound of claim 3 or a pharma- ceutically acceptable salt thereof.

33. A pharmaceutical composition comprising the compound of claim 4 or a pharma- ceutically acceptable salt thereof.

34. A pharmaceutical composition comprising the compound of claim 5 or a pharma- ceutically acceptable salt thereof.

35. The pharmaceutical composition of claim 30 for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

36. A pharmaceutical composition described in any one of claims 31 to 34 for treating castration-resistant prostate cancer, adrenocortical carcinoma, Leydig tumor, hormone-sensitive prostate cancer, breast cancer, Cushing's syndrome, or primary aldosteronism.

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