Quaternary ring structure-substituted tertiary amide derivatives

Abstract

This disclosure provides: tertiary amide derivatives substituted with a four-membered ring structure and usable as pharmaceuticals, and pharmaceutically acceptable salts thereof; and pharmaceutical compositions comprising a component or agent for treating or preventing pathological states involving CBP / P300, the agent comprising the composition. More specifically, this disclosure provides compounds represented by formula (1) [where A represents CHF or CH2, B represents formula (B-1), ring Q represents a substituted six- to ten-membered aromatic ring or a substituted five- to ten-membered aromatic heterocyclic ring, and Z represents O, -N(R 7a )-、Substitutable hexa- to decavalent aromatic ring groups, substituted penta- to decavalent aromatic heterocyclic groups, or substituted tetra- to decavalent non-aryl heterocyclic groups, and R 1 R 2a R 2b R 3 R 4 and R 5 As described in the instructions, or its pharmaceutically acceptable salt.

Description

[Technical Field] This disclosure relates to quaternary carbon-substituted tertiary amide derivatives that can be used as pharmaceuticals and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the thereof, therapeutic agents and / or preventive agents comprising the compositions for conditions involving CBP / P300, etc. [Background Technology] Chromosomes dynamically regulate gene replication and transcription by altering their higher-order structure through methylation of their structural element DNA and various modifications of histones (including histones H2A, H2B, H3, and H4) such as acetylation, methylation, phosphorylation, and ubiquitination (Non-Patent Literature 1).

[0003] Histone acetylation is a frequent post-translational modification in eukaryotes and plays a role in promoting gene transcription. Histone acetyltransferases (HATs), which function during histone acetylation, are enzymes that transfer acetyl groups to the lysine side chains of histones. Based on amino acid sequence homology, higher-order structure, and function, they are broadly classified into four types: CBP / P300 (E1A-binding protein p300 / CREB-binding protein), GCN5 / PCAF (general control nonrepressed-protein 5 / P300 / CBP-associated factor), MYST (MOZ, Ybf2 / Sas3, Sas2, and Tip60), and Rtt109 (Regulator of Tyl Transposition gene production 109). P300 and its paralog CBP share 90% or more amino acid sequence homology and, in addition to the HAT domain, also contain the CH1 / CH2 / CH3 domain (a cysteine-histidine rich domain), the KIX domain, the bromine domain, etc. (Non-Patent Literature 2).

[0004] CBP / P300 were each discovered as corresponding binding partners for E1A adenovirus proteins and cAMP regulator enhancer-binding proteins (Non-Patent Literature 3-5). Subsequently, CBP / P300 were found to possess HAT activity (Non-Patent Literature 6 and 7), and their substrate specificity was also studied in detail. As a result, it was reported that they not only acetylate lysine residues of histones (H2A, H2B, H3, and H4), but also acetylate p53 (Non-Patent Literature 8), MyoD (Non-Patent Literature 9), STAT3 (Non-Patent Literature 10), and androgen receptors (Non-Patent Literature 11), etc. In addition, CBP / P300 participate in a large number of biological reactions, such as division, proliferation, and differentiation (Non-Patent Literature 12).

[0005] CBP / P300 has been reported to play an important role in the proliferation of various cancers. Examples include prostate cancer (non-patent literature 13 and 14), liver cancer (non-patent literature 15 and 16), lung cancer (non-patent literature 17 to 19), breast cancer (non-patent literature 20), colon and stomach cancer (non-patent literature 21), hematologic malignancies (non-patent literature 22 and 23), pancreatic cancer (non-patent literature 24), bladder cancer (non-patent literature 25), gastrointestinal stromal tumors (non-patent literature 26), midline carcinoma of the nucleus vertebrae (NUT) (non-patent literature 27), ovarian cancer (non-patent literature 28), and malignant rhabdoid tumors and epithelioid sarcomas (patent literature 11).

[0006] As can be seen from the above, drugs that inhibit CBP / P300 function are expected to be used as anti-tumor agents. To date, small molecule inhibitors targeting the HAT domain of CBP / P300 have been disclosed in patent documents 1 to 10 and non-patent documents 29.

[0007] [List of Citations] [Patent Literature] [PTL 1] WO 2016 / 044770 [PTL 2] WO 2018 / 235966 [PTL 3] WO 2019 / 111980 [PTL 4] WO 2019 / 049061 [PTL 5] WO 2019 / 161157 [PTL 6] WO 2019 / 161162 [PTL 7] WO 2020 / 176558 [PTL 8] WO 2019 / 201291 [PTL 9] WO 2020 / 108500 [PTL 10] WO 2020 / 198567 [PTL 11] WO 2022 / 138944 [Non-patent literature] [NPL 1] Genes Dev.2002,16(14):1739-1742. [NPL 2] Mol Genet Metab.2016,119(1-2):37-43. [NPL 3] Virology.1985,147(1):142-153. [NPL 4] Mol Cell Biol.1986,6(5):1579-1589. [NPL 5] Nature.1993,365(6449):855-859. [NPL 6] Cell.1996,87(5):953-959. [NPL 7] Nature.1996,384(6610):64 1-6 43. [NPL 8] Cell.1997,90(4):595-606. [NPL 9] J Biol Chem.2000,275(44):34359-34364. [NPL 10] Science.2005,307(5707):269-273. [NPL 11] J Biol Chem.2000,275(27),20853-20860. [NPL 12] J Cell Sci.2001,114(Pt 13):2363-2373. [NPL 13] Adv Exp Med Biol.2008;617:535-540. [NPL 14] Prostate.2008,68(10):1097-1104. [NPL 15] Cancer Lett.2011,310(2):140-147. [NPL 16] J Transl Med. 2011, 9:5. [NPL 17] Int J Clin Exp Pathol.2014, 7(2):760-767. [NPL 18] Nat Genet.2012,44(10):1104-1110. [NPL 19] Clin Cancer Res.2005,11(2 Pt 1):512-519. [NPL 20] Genes Cancer.2016,7(3-4):98-109. [NPL 21] Oncogene.1996,12(7):1565-1569. [NPL 22] Proc Natl Acad Sci US A.1997,9 4(16):8732-8737. [NPL 23] Blood. 2012, 120(15) 3058-3068. [NPL 24] Nat Genet. 2000, 24(3): 300-303. [NPL 25] Nat Genet. 2011, 43(9): 875-878. [NPL 26] Oncol Rep.2016,36(5):2763-2770. [NPL 27] J Biol Chem.2015,290(5):2744-2758. [NPL 28] Oncotarget.2016,7(14):17790-17804. [NPL 29] Bioorg Med Chem Lett. 2021,39:127854-127859. [Summary of the Invention] [Solution to the problem] This disclosure provides a compound that exerts its anticancer effect by inhibiting CBP / P300, which has been reported to be highly expressed, mutated, or overactive in various cancers. Preferably, this disclosure provides a compound having high CBP / P300 inhibitory activity, as well as high water solubility sufficient to exert an anticancer effect when administered intravenously and high oral absorption sufficient to exert an anticancer effect when administered orally. In other words, this disclosure provides a compound that is extremely useful as an anticancer agent for the treatment of a wide range of cancer types.

[0009] As a result of in-depth research, the inventors have discovered that compounds represented by formula (1) or pharmaceutically acceptable salts thereof (hereinafter also referred to as "the compounds of this disclosure") have a potent inhibitory effect on the HAT domain of CBP / P300, thereby exhibiting excellent anticancer effects and exhibiting high oral absorption and high water solubility suitable for oral and intravenous administration, thus completing this disclosure.

[0010] Therefore, the contents of this disclosure are as follows.

[0011] [Project 1] Compounds represented by the following formula: [Chemical Formula 1] in A represents CHF or CH2. B represents the following formula (B-1): [Chemical Formula 2] in Indicates the bonding position with the nitrogen atom on the hydantoin ring. Ring Q represents an optionally substituted 6- to 10-membered aromatic hydrocarbon ring or an optionally substituted 5- to 10-membered aromatic heterocycle. Z represents -O-, -N(R) 7a )-, optionally substituted 6- to 10-membered divalent aromatic ring groups, optionally substituted 5- to 10-membered divalent aromatic heterocyclic groups, or optionally substituted 4- to 10-membered divalent non-aryl heterocyclic groups, R 1 C represents optional substitution 1-6 Alkyl or optionally substituted C 3-10 Alicyclic groups, R 2a and R 2b Each independently represents an optional substitution of C. 1-6 Alkyl, wherein R 2a and R 2bTogether with the carbon atoms they are attached to, they can form optionally substituted C atoms. 3-6 Cycloalkyl or optionally substituted 4- to 6-membered divalent nonaryl heterocyclic groups, R 3 C represents optional substitution 6-10 aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted C 3-10 Alicyclic groups or optionally substituted 4- to 10-membered non-aryl heterocyclic groups, R 4 C represents a single bond or optional substitution. 1-6 Alkylene, optionally substituted C 3-10 Cycloalkyl or optionally substituted 4- to 10-membered divalent nonaryl heterocyclic groups, R 5 C represents hydrogen atom, halogen atom, hydroxyl group, cyano group, or optional substitution. 1-6 Alkyl, optionally substituted C 1-6 alkenyl, optionally substituted C 1-6 alkynyl group, optionally substituted C 1-3 Alkoxy, -NR 7b R 7c -SO2R 7d -CONR 7e R 7f Optional substitution of C 3-10 Alicyclic groups, optionally substituted 4- to 10-membered non-aryl heterocyclic groups, optionally substituted C 6-10 Aryl or optionally substituted 5 to 10-membered heteroaryl, and R 7a R 7b R 7c R 7d R 7e and R 7f Each of the C atoms independently represents a hydrogen atom or an optional substituted C atom. 1-6 alkyl, Or its pharmaceutically acceptable salt.

[0012] [Project 2] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein R 1 R 2a R 2b R 3 R 4 R 5 R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9aR 9b The optionally substituted 6- to 10-membered aromatic rings in rings Q and Z, the optionally substituted 5- to 10-membered aromatic heterocycles, the optionally substituted 6- to 10-membered divalent aromatic ring groups, the optionally substituted 5- to 10-membered divalent aromatic heterocycle groups, and the optionally substituted C 6-10 aryl, the optionally substituted 5- to 10-membered heteroaryl, the optionally substituted 4- to 10-membered non-aryl heterocyclic group, the optionally substituted C 1-6 Alkyl groups, the optionally substituted C 1-6 alkenyl, the optionally substituted C 1-6 alkynyl group, the optional substituted C 3-10 Alicyclic groups, the optionally substituted C 3-6 Cycloalkylene, the optionally substituted 4- to 6-membered divalent nonaryl heterocyclic group, the optionally substituted C 1-6 Alkylene, the optionally substituted C 3-10 Cycloalkylene, the optionally substituted 4- to 10-membered divalent nonaryl heterocyclic group, or the optionally substituted C-membered group 1-3 Each alkoxy group may be independently substituted by one to five identical or different substituents selected from the following: (1) Halogen atom, (2) Hydroxyl group, (3) C 6-10 Aryl, (4) 5- to 12-membered heteroaryl groups, (5) C 1-6 alkyl, (6) C 2-6 alkenyl, (7) C 2-6 alkynyl group, (8) C 1-6 Alkoxy (9) C 1-6 Alkylthio, (10) C 3-10 Alicyclic groups, (11) 3 to 10-membered non-aryl heterocyclic groups, (12) Carboxyl group, (13) -COR 10 , (14) -CO2R 10 , (15) -CONR 11 R 12 , (16) -NR 11 R 12 , (17) -NR13 COR 10 , (18) -NR 13 CO2R 10 , (19) -NR 13 SO2R 10 , (20) -NR 13 CONR 11 R 12 , (21) -NR 13 SO2NR 11 R 12 , (22) -SO2R 10 , (23) -SO2NR 11 R 12 , (24) -OCOR 10 , (25) -OCO2R 10 , (26) -OCONR 11 R 12 , (27) sulfonyl, (28) Phosphate group, (29) Cyano, and (30) Nitro, Wherein (3) C 6-10 Aryl, (4) 5 to 12-membered heteroaryl, (5) C 1-6 Alkyl, (6) C 2-6 alkenyl, (7)C 2-6 alkynyl group, (8) C 1-6 Alkoxy, (9) C 1-6 Alkylthio, (10) C 3-10 The alicyclic group and (11) the 3 to 10-membered nonaryl heterocyclic group may be optionally substituted by 1 to 5 identical or different substituents selected from the following: (a) Halogen atom, (b) Hydroxyl group, (c) C 6-10 Aryl, (d) 5 to 12-benzyl aryl, (e) C 1-6 alkyl, (f) C 2-6 alkenyl, (g) C 2-6alkynyl group, (h) C 1-6 Alkoxy (i) C 3-10 Alicyclic groups, (j) 3- to 10-membered non-aryl heterocyclic groups, (k) carboxyl group, (l) -COR 10 , (m) -CO2R 10 , (n) -CONR 11 R 12 , (o) -NR 11 R 12 , (p) -NR 13 COR 10 , (q) -NR 13 SO2R 10 , (r) -SO2R 10 , (s) -SO2NR 11 R 12 , (t) sulfonyl, (u) Phosphate group, (v) cyano, and (w) Nitro, R 10 If multiple cases exist, each is independently designated as C. 1-6 alkyl, R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 Alkyl groups, and if multiple R groups are present 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which it is attached, it can form a 3 to 8-membered nitrogen-containing non-aryl heterocyclic group, and R 13 It is a hydrogen atom or a carbon atom. 1-6 alkyl.

[0013] [Project 3] The compound or a pharmaceutically acceptable salt thereof found in any one of items 1 to 2, wherein R1 R 2a R 2b R 3 R 4 R 5 R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9a R 9b The optionally substituted 6- to 10-membered aromatic rings in rings Q and Z, the optionally substituted 5- to 10-membered aromatic heterocycles, the optionally substituted 6- to 10-membered divalent aromatic ring groups, the optionally substituted 5- to 10-membered divalent aromatic heterocycle groups, and the optionally substituted C 6-10 aryl, the optionally substituted 5- to 10-membered heteroaryl, the optionally substituted 4- to 10-membered non-aryl heterocyclic group, the optionally substituted C 1-6 Alkyl groups, the optionally substituted C 1-6 alkenyl, the optionally substituted C 1-6 alkynyl group, the optional substituted C 3-10 Alicyclic groups, the optionally substituted C 3-6 Cycloalkylene, the optionally substituted 4- to 6-membered divalent nonaryl heterocyclic group, the optionally substituted C 1-6 Alkylene, the optionally substituted C 3-10 Cycloalkylene, the optionally substituted 4- to 10-membered divalent nonaryl heterocyclic group, or the optionally substituted C-membered group 1-3 Each alkoxy group may be independently substituted by one to five identical or different substituents selected from the following: (1) Halogen atom, (2) Hydroxyl group, (3) C 6-10 Aryl, (4) 5- to 12-membered heteroaryl groups, (5) C atoms substituted with 1 to 3 halogen atoms 1-6 alkyl, (6) C 2-6 alkenyl, (7) C 2-6 alkynyl group, (8) C 1-6 Alkoxy (9) C 3-10 Alicyclic groups, (10) 3 to 10-membered non-aryl heterocyclic groups, (11) Carboxyl group, (12) -COR 10 , (13) -CO2R 10 , (14) -CONR 11 R 12 , (15) -NR 11 R 12 , (16) -SO2R 10 , (17) -SO2NR 11 R 12 , (18) Sulfonate, (19) Phosphate group, (20) Cyano, and (21) Nitro, R 10 If multiple cases exist, each is independently designated as C. 1-6 Alkyl, and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 Alkyl groups, and if multiple R groups are present 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0014] [Project 4] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 1 to 3, wherein R 1 R 2a R 2b R 3 R 4 R 5 R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9a R 9bThe optionally substituted 6- to 10-membered aromatic rings in rings Q and Z, the optionally substituted 5- to 10-membered aromatic heterocycles, the optionally substituted 6- to 10-membered divalent aromatic ring groups, the optionally substituted 5- to 10-membered divalent aromatic heterocycle groups, and the optionally substituted C 6-10 aryl, the optionally substituted 5- to 10-membered heteroaryl, the optionally substituted 4- to 10-membered non-aryl heterocyclic group, the optionally substituted C 1-6 Alkyl groups, the optionally substituted C 1-6 alkenyl, the optionally substituted C 1-6 alkynyl group, the optional substituted C 3-10 Alicyclic groups, the optionally substituted C 3-6 Cycloalkylene, the optionally substituted 4- to 6-membered divalent nonaryl heterocyclic group, the optionally substituted C 1-6 Alkylene, the optionally substituted C 3-10 Cycloalkylene, the optionally substituted 4- to 10-membered divalent nonaryl heterocyclic group, or the optionally substituted C-membered group 1-3 Each alkoxy group may be independently substituted by one to five identical or different substituents selected from the following: (1) Halogen atom, (2) Hydroxyl group, (3) Phenyl, (4) 5- to 6-heteroaryl compounds, (5) C atoms substituted with 1 to 3 halogen atoms 1-6 alkyl, (6) C 1-6 Alkoxy (7) C 3-7 Alicyclic groups, (8) 3- to 7-membered non-aryl heterocyclic groups, (9) -COR 10 , (10) -CO2R 10 , (11) -CONR 11 R 12 , (12) -NR 11 R 12 , (13) -SO2R 10 , (14) -SO2NR 11 R 12 ,and (15) Cyano group, R 10 If multiple cases exist, each is independently designated as C. 1-6Alkyl, and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 Alkyl groups, and if multiple R groups are present 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0015] [Project 5] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 1 to 4, wherein B is one of the following formulas: (B-2), (B-3), or (B-4): [Chemical Formula 3] in Indicates the bonding position with the nitrogen atom on the hydantoin ring. 'a' represents 0, 1, or 2. b represents 1 or 2. R 8 C represents a hydrogen atom or an optional substitution. 1-6 Alkyl, and R 9a and R 9b Each C atom independently represents a hydrogen atom, a halogen atom, or an optionally substituted C atom. 1-6 alkyl.

[0016] [Project 6] The compound or a pharmaceutically acceptable salt thereof found in any one of items 1 to 5, wherein R 1 C atoms are optionally substituted with 1 to 3 fluorine atoms. 1-3 alkyl.

[0017] [Project 7] The compound or a pharmaceutically acceptable salt thereof found in any one of items 1 to 6, wherein R 1 It is CF3.

[0018] [Project 8] The compound or a pharmaceutically acceptable salt thereof found in any one of items 1 to 7, wherein R 3 C 6-10 Aryl (the aryl group is optionally replaced by 1 to 3 identical or different C atoms selected from halogen atoms and optionally substituted C atoms) 1-6Alkyl substituents) or 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0019] [Project 9] The compound or a pharmaceutically acceptable salt thereof described in any one of items 1 to 8, wherein R 3 It is 4-fluorophenyl, 4-(trifluoromethyl)phenyl or 4-fluoro-2-pyridyl.

[0020] [Project 10] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 1 to 9, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl.

[0021] [Project 11] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 1 to 10, wherein ring Q is a 6- to 10-membered aromatic ring (the aromatic ring is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0022] [Project 12] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 1 to 11, wherein ring Q is a benzene ring (the benzene ring is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0023] [Project 13] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 1 to 12, wherein a is 1 or 2.

[0024] [Project 14] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 1 to 13, wherein a is 1.

[0025] [Project 15] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 1 to 14, wherein b is 1.

[0026] [Project 16] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 1 to 15, wherein a is 1 and b is 1.

[0027] [Project 17] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (2): [Chemical Formula 4] in A represents CHF or CH2. R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. Z represents -O-, 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Halogen atoms, hydroxyl group Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 Represents a hydrogen atom or a halogen atom. R 7b R 7c R 7d R 7e and R7f Each represents independently hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0028] [Project 18] The compound described in Item 17 or a pharmaceutically acceptable salt thereof, wherein A is CHF.

[0029] [Project 19] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 17 or 18, wherein R 6 It is a hydrogen atom.

[0030] [Project 20] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 17 to 19, wherein Z is 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0031] [Project 21] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 17 to 20, wherein Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11R 12 (Substituents).

[0032] [Project 22] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 17 to 21, wherein R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0033] [Project 23] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 17 to 22, wherein R 5 for hydrogen atom, Halogen atoms, Cyano, -NR 7b R 7c , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0034] [Project 24] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (3): [Chemical Formula 5] in R3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0035] [Project 25] The compound described in item 24 or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl.

[0036] [Project 26] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 or 25, wherein R 3 It is 4-fluoro-2-pyridyl.

[0037] [Project 27] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 26, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

[0038] [Project 28] The compound or a pharmaceutically acceptable salt thereof found in any one of items 24 to 27, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

[0039] [Project 29] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 28, wherein R 4 It is either azetidinylene or piperidinylene.

[0040] [Project 30] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 29, wherein R 5 for C 1-6 alkyl, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0041] [Project 31] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 30, wherein R 5 for C 1-3 alkyl, or 4 to 6-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0042] [Project 32] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 31, wherein R 5 It is a methyl group.

[0043] [Project 33] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 31, wherein R 5 It is an oxocyclic butyl group.

[0044] [Project 34] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 24 to 33, wherein R 11 and R12 It is a methyl group.

[0045] [Project 35] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (4): [Chemical Formula 6] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0046] [Project 36] The compound described in item 35 or a pharmaceutically acceptable salt thereof, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

[0047] [Project 37] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 35 or 36, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

[0048] [Project 38] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 35 to 37, wherein R 4 It is a nitrosobutane.

[0049] [Project 39] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 35 to 38, wherein R 5 for C 1-6 alkyl, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0050] [Project 40] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 35 to 39, wherein R 5 for C 1-3 alkyl, or 4 to 6-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0051] [Project 41] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 35 to 40, wherein R 5 It is an oxocyclic butyl group.

[0052] [Project 42] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (5): [Chemical Formula 7] in A represents CHF or CH2. R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. Z represents 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Halogen atoms, hydroxyl group Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-3 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 Represents a hydrogen atom or a halogen atom. R 7a R 7b R 7c R 7d R 7e and R 7f Each represents independently hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 8 express hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0053] [Project 43] The compound described in Item 42 or a pharmaceutically acceptable salt thereof, wherein A is CHF.

[0054] [Project 44] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 42 or 43, wherein R 6 It is a hydrogen atom.

[0055] [Project 45] The compound or a pharmaceutically acceptable salt thereof found in any one of items 42 to 44, wherein Z is 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0056] [Project 46] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 42 to 45, wherein Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R12 (Substituents).

[0057] [Project 47] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 42 to 46, wherein R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0058] [Project 48] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 42 to 47, wherein R 5 for hydrogen atom, hydroxyl group Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 7d C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0059] [Project 49] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 42 to 48, wherein R 8 C 1-6 alkyl.

[0060] [Project 50] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 42 to 49, wherein R 8 It is a methyl group.

[0061] [Project 51] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (6): [Chemical Formula 8] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, hydroxyl group Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0062] [Project 52] The compound described in item 51 or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl.

[0063] [Project 53] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 51 or 52, wherein R 3 It is 4-fluoro-2-pyridyl.

[0064] [Project 54] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 51 to 53, wherein R 4 for Single key, or C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0065] [Project 55] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 51 to 54, wherein R 4 It is a single key.

[0066] [Project 56] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 51 to 54, wherein R 4 C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0067] [Project 57] The compound or a pharmaceutically acceptable salt thereof found in any one of items 51 to 56, wherein R 5 for hydroxyl group Cyano, C 1-6 alkyl, C 3-10 Alicyclic groups, or 4 to 10-membered non-aryl heterocyclic groups.

[0068] [Project 58] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 51 to 57, wherein R 5 It is a methyl group.

[0069] [Project 59] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 51 to 57, wherein R 5 It is an oxocyclic butyl group.

[0070] [Project 60] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (7): [Chemical Formula 9] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0071] [Project 61] The compound described in item 60 or a pharmaceutically acceptable salt thereof, wherein R 4 for Single key, or C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0072] [Project 62] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 60 or 61, wherein R 4 It is a single key.

[0073] [Project 63] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 60 to 62, wherein R 4 C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0074] [Project 64] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 60 to 63, wherein R 5 for C 1-6 alkyl, or Cyano group.

[0075] [Project 65] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 60 to 64, wherein R 5 It is a methyl group.

[0076] [Project 66] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 60 to 64, wherein R 5 It is a cyano group.

[0077] [Project 67] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (8): [Chemical Formula 10] in A represents CHF or CH2. R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. Z represents 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Halogen atoms, hydroxyl group Cyano, -NR 7b R 7c , -SO2R7d , -CONR 7e R 7f , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-3 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 Represents a hydrogen atom or a halogen atom. R7a R 7b R 7c R 7d R 7e and R 7f Each represents independently hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 9a and R 9b Each represents independently hydrogen atom, Halogen atoms, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0078] [Project 68] The compound described in Item 67 or a pharmaceutically acceptable salt thereof, wherein A is CHF.

[0079] [Project 69] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 67 or 68, wherein R 6 It is a hydrogen atom.

[0080] [Project 70] The compound or a pharmaceutically acceptable salt thereof found in any one of items 67 to 69, wherein Z is 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0081] [Project 71] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 67 to 70, wherein Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0082] [Project 72] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 67 to 71, wherein R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0083] [Project 73] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 67 to 72, wherein R 5 for hydrogen atom, Cyano, -NR 7b R 7c , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0084] [Project 74] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 67 to 73, wherein R 9a and R 9b It is a fluorine atom.

[0085] [Project 75] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (9): [Chemical Formula 11] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Cyano, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 acetylenic group, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0086] [Project 76] The compound described in item 75 or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl.

[0087] [Project 77] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 75 or 76, wherein R 3 It is 4-fluoro-2-pyridyl.

[0088] [Project 78] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 75 to 77, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

[0089] [Project 79] The compound or a pharmaceutically acceptable salt thereof found in any one of items 75 to 78, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

[0090] [Project 80] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 75 to 79, wherein R 4 It is a nitrosobutane.

[0091] [Project 81] The compound or a pharmaceutically acceptable salt thereof found in any one of items 75 to 80, wherein R 5 It consists of 4 to 10-membered non-aryl heterocyclic groups.

[0092] [Project 82] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 75 to 81, wherein R 5 It is a 4- to 6-membered non-aryl heterocyclic group.

[0093] [Project 83] The compound or a pharmaceutically acceptable salt thereof found in any one of items 75 to 82, wherein R 5 It is an oxocyclic butyl group.

[0094] [Project 84] The compound described in Project 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (10): [Chemical Formula 12] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Cyano, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 acetylenic group, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0095] [Project 85] The compound described in item 84 or a pharmaceutically acceptable salt thereof, wherein R 4It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

[0096] [Project 86] The compound or a pharmaceutically acceptable salt thereof as described in any one of items 84 or 85, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

[0097] [Project 87] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 84 to 86, wherein R 4 It is a nitrosobutane.

[0098] [Project 88] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 84 to 87, wherein R 5 It consists of 4 to 10-membered non-aryl heterocyclic groups.

[0099] [Project 89] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 84 to 88, wherein R 5 It is a 4- to 6-membered non-aryl heterocyclic group.

[0100] [Project 90] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 84 to 89, wherein R 5 It is an oxocyclic butyl group.

[0101] [Project 91] The compound described in Project 1, or a pharmaceutically acceptable salt thereof, is selected from the following compounds: N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide (Example 1). 2-[(1'S)-5'-{1-[(3-fluoro-1-methylazacyclobutane-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxacyclobutane-3-yl]acetamide (Example 2). 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxecyclobutane-3-yl]acetamide (Example 3). N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]acetamide (Example 4). N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxecyclobutane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]acetamide (Example 5). N-[(5-fluoropyridin-2-yl)methyl]-2-[(1'S)-5'-{1-[1-(oxecyclobutane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[3-(trifluoromethyl)oxecyclobutane-3-yl]acetamide (Example 6). 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide (Example 7). N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(5-fluoropyridin-2-yl)methyl]-2-[(1'S)-5'-{1-[1-(oxecyclobutan-3-yl)azacyclobutan-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]acetamide (Example 8). N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)azacyclobutan-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]acetamide (Example 9). 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 10). 2-{(1'S,3'R)-5'-[1-(2-cyanopropyl-2-yl)-1H-pyrazol-4-yl]-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 11). N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 12). 2-{(1'S)-5'-[1-(2-cyanopropyl-2-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 13). 2-[(1'S,3'R)-3'-fluoro-5'-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide (Example 14). 2-[(1'S,3'R)-3'-fluoro-5'-(5-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 15). 2-[(1'S)-5'-(5-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 16). 2-[(1'S,3'R)-3'-fluoro-5'-(3-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 17). 2-[(1'S)-5'-(3-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 18). 2-{(1'S,3'R)-3'-fluoro-5'-[1-(oxan-4-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (2-{(1′S,3′R)-3′-fluoro-5′-[1-(oxan-4-yl)- 1H-pyrazol-4-yl]-2,5-dioxo-2′,3′-dihydrospiro[imidazolidine-4,1′-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide) (Example 19), 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 20). N-[(5-fluoropyridin-2-yl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 21). 2-[(1'S,3'R)-5'-(1-{[3-(dimethylamino)oxetane-3-yl]methyl}-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide (Example 22). 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)piperidin-4-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide (Example 23). 2-{(1'S,3'R)-3'-fluoro-5'-[1-(oxecyclobutan-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutan-3-yl]acetamide (Example 24). 2-[(1'S,3'R)-3'-fluoro-5'-{1-[(oxecyclobutane-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 25). 2-{(1'S,3'R)-5'-[1-(2-cyanopropyl-2-yl)-1H-pyrazol-4-yl]-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 26). 2-{(1'S,3'R)-3'-fluoro-5'-[1-(1-hydroxy-2-methylpropyl-2-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 27). 2-[(1'R,3'S)-3',6'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 28). 2-[(1'S,3'R)-3',6'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 29). 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 30). 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 31). 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 32). 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 33). 2-[(1'S,3'R)-5'-(1-cyclobutyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 34), and 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]-N-{[4-(trifluoromethyl)phenyl]methyl}acetamide (Example 35).

[0102] [Project 92] The compound described in Project 1, or a pharmaceutically acceptable salt thereof, is selected from the following compounds: 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide (Example 7). 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 10). 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 20). 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)piperidin-4-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide (Example 23). 2-{(1'S,3'R)-3'-fluoro-5'-[1-(oxecyclobutan-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutan-3-yl]acetamide (Example 24). 2-[(1'S,3'R)-3'-fluoro-5'-{1-[(oxecyclobutane-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 25). 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 30). 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 31). 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 32). 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 33), and 2-[(1'S,3'R)-5'-(1-cyclobutyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide (Example 34).

[0103] [Project 93] A drug comprising, as an active ingredient, any one of items 1 to 92, a compound or a pharmaceutically acceptable salt thereof.

[0104] [Project 94] A pharmaceutical composition comprising any one of items 1 to 92 or a pharmaceutically acceptable salt thereof.

[0105] [Project 95] A therapeutic and / or preventive agent for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disease, comprising any one of items 1 to 92 or a pharmaceutically acceptable salt thereof as an active ingredient.

[0106] [Project 96] A therapeutic and / or preventive agent for cancer, comprising, as an active ingredient, any one of items 1 to 92, a compound or a pharmaceutically acceptable salt thereof.

[0107] [Project 97] The therapeutic and / or preventive agents described in Item 95 or 96, wherein the cancer is at least one type of cancer selected from SMARC-deficient cancer, SS18-SSX fusion cancer, and ARID-deficient cancer.

[0108] [Project 98] Therapeutic and / or preventative agents as described in any one of items 95 to 97, wherein the cancer is selected from malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordoid meningioma, neuroepithelial tumor, glial neuron tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraosseous myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, basal squamous cell carcinoma of the sinus, esophageal cancer, papillary thyroid carcinoma, follicular thyroid carcinoma, gastrointestinal stromal tumor, undifferentiated rhabdoid tumor of the pancreas, gastrointestinal rhabdoid tumor, renal medullary carcinoma, endometrial cancer, and vulvar myoepithelioma. It includes at least one type of cancer among the following: scleroderma, colon cancer, mesothelioma, lung adenocarcinoma, large cell lung cancer, pulmonary neuroendocrine tumor, gastroesophageal junction cancer, gastric cancer, bladder cancer, lung squamous cell carcinoma, pancreatic cancer, medulloblastoma, renal clear cell carcinoma, liver cancer, pleomorphic carcinoma, thoracic sarcoma, ovarian small cell carcinoma, primary gallbladder tumor, uterine sarcoma, ovarian granulosa cell tumor, adrenocortical carcinoma, small cell lung cancer, ovarian cancer, uterine cancer, neuroblastoma, mucinous ovarian tumor, nasal cavity and sinus cancer, intrathoracic sarcoma, bile duct cancer, neuroblastoma, melanoma, breast cancer, undifferentiated round cell sarcoma, rhabdomyosarcoma, and Ewing sarcoma.

[0109] [Project 99] A method for treating and / or preventing cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disease, comprising administering to a patient in need a therapeutically effective and / or preventively effective amount of any one of items 1 to 92, or a pharmaceutically acceptable salt thereof.

[0110] [Project 100] Use of any compound or pharmaceutically acceptable salt thereof from any one of items 1 to 92 in the manufacture of therapeutics and / or preventatives for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disorders.

[0111] [Project 101] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 1 to 92, is used for the treatment and / or prevention of cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disorders.

[0112] [Project 102] The compound or a pharmaceutically acceptable salt thereof, as described in any one of items 1 to 92, is used in combination with another drug or a pharmaceutically acceptable salt thereof to treat cancer, wherein the other drug is at least one selected from drugs such as hormone therapy agents, chemotherapy agents, immunotherapy agents, and agents that inhibit the action of cell growth factors and their receptors.

[0113] [Project 103] A pharmaceutical composition comprising any one of items 1 to 92, or a pharmaceutically acceptable salt thereof, comprising a combination with another drug, wherein the other drug is at least one selected from drugs such as hormone therapy agents, chemotherapeutic agents, immunotherapy agents, and agents that inhibit the action of cell growth factors and their receptors.

[0114] [The effects of the invention] This disclosure provides CBP / P300 inhibitors, including tertiary amide derivatives substituted with quaternary carbon and their pharmaceutically acceptable salts.

[0115] This disclosure provides medicaments for inhibiting CBP / P300 function, applicable to a wide range of diseases and administration methods. This disclosure also provides compounds represented by formula (1), which are tertiary amide derivatives substituted with quaternary carbons, and are available as such medicaments, as well as related medicaments.

[0116] The disclosed compounds exhibit excellent CBP / P300 inhibitory activity and can be used as therapeutic agents for diseases involving CBP / P300, and are particularly suitable for patients with cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic diseases.

[0117] [Explanation of the Implementation Plan] The present disclosure is described in more detail below. Throughout this specification, unless otherwise specified, singular expressions should be understood to encompass the concept of their plural forms. Therefore, unless otherwise specified, singular articles (e.g., "a," "an," "the," etc. in the English context) should also be understood to encompass the concept of their plural forms. Unless otherwise specified, the terms used herein should also be understood to be used in their usual meaning in the art. Therefore, unless otherwise defined, all terms and scientific and technical terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. In the event of any conflict, this specification (including definitions) shall prevail.

[0118] The terminology used in this article is described below.

[0119] As used herein, there is no particular limitation on the number of substituents in a group defined as “optionally substituted”, provided that they are substituted. When the number of substituents is specified and described as being “substituted” by that number of substituents, it means that the group is substituted by that number of substituents. For example, “substituted by 2 to 5 substituents” means substituted by 2, 3, 4, or 5 substituents. Unless otherwise specified, the description of each group also applies when it is a substituent or part of another group.

[0120] "Halogen atoms" include fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, etc. Fluorine atoms or chlorine atoms are preferred.

[0121] “C 1-6 "Alkyl" refers to a straight-chain or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and "C6 alkyl" refers to an alkyl group having 6 carbon atoms. Other numbers also apply. C 1-6 Alkyl groups are preferably "C" 1-4 Alkyl group, and more preferably C 1-3 Alkyl group. "C" 1-3 Specific examples of "alkyl" include methyl, ethyl, propyl, 1-methylethyl, etc. "C 1-4 Specific examples of "alkyl" include those mentioned above, such as "C". 1-3 Besides specific examples of "alkyl", it also includes butyl, 1,1-dimethylethyl, 1-methylpropyl, 2-methylpropyl, etc. "C" 1-6 Specific examples of "alkyl" include those mentioned above, such as "C". 1-4In addition to specific examples of "alkyl", it also includes pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylbutyl, 2-methylbutyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, hexyl, etc.

[0122] “C 2-6 "Alkenyl" refers to a straight-chain or branched unsaturated hydrocarbon group with 2 to 6 carbon atoms and containing 1 to 3 double bonds. 2-6 "Alkenyl" is preferably "C" 2-4 "Alkenyl". "C" 2-4 Specific examples of "alkenyl" include vinyl, propenyl, methacryl, butenyl, etc. "C" 2-6 Specific examples of "alkenyl" include the "C" mentioned above. 2-4 In addition to specific examples of "alkenyl", it also includes pentenyl, hexenyl, etc.

[0123] “C 2-6 "Alkyne" refers to a straight-chain or branched unsaturated hydrocarbon group with 2 to 6 carbon atoms and containing a triple bond. 2-6 "Alkyne group" is preferably "C 2-4 "Alkyne group". "C" 2-4 Specific examples of "alkynyl" include propynyl, methylpropynyl, butynyl, etc. 2-6 Specific examples of "alkynyl group" include the "C" group mentioned above. 2-4 Besides specific examples of "alkynyl", it also includes methylbutynyl, pentyynyl, hexynyl, etc.

[0124] “C 1-6 "Alkoxy" is "C 1-6 "alkyloxy", and "C" 1-6 The "alkyl" part and "C" 1-6 The definition of "alkyl" is the same. "C" 1-6 "Alkoxy" is preferably "C" 1-4 "alkoxy", and more preferably "C" 1-3 Alkoxy group. "C" 1-3 Specific examples of "alkoxy" include methoxy, ethoxy, propoxy, 1-methylethoxy, etc. "C" 1-4 Specific examples of "alkoxy" include the "C" mentioned above. 1-3 Besides specific examples of "alkoxy," it also includes butoxy, 1,1-dimethylethoxy, 1-methylpropoxy, 2-methylpropoxy, etc. "C" 1-6 Specific examples of "alkoxy" include the "C" mentioned above. 1-4 In addition to specific examples of "alkoxy", it also includes pentoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylbutoxy, 2-methylbutoxy, 4-methylpentoxy, 3-methylpentoxy, 2-methylpentoxy, 1-methylpentoxy, hexoxy, etc.

[0125] “C 1-6 The "C" of "alkylthio" 1-6 The "alkyl" part and "C" 1-6 The definition of "alkyl" is the same. "C" 1-6 "alkylthio" is preferably "C 1-4 "alkylthio" and more preferably "C 1-3 "alkylthio" "C" 1-3 Specific examples of "alkylthio" include methylthio, ethylthio, propylthio, 1-methylethylthio, etc. "C 1-4 Specific examples of "alkylthio" include the "C" mentioned above. 1-3 Besides specific examples of "alkylthio", other examples include butylthio, 1,1-dimethylethylthio, 1-methylpropylthio, 2-methylpropylthio, etc. "C 1-6 Specific examples of "alkylthio" include the "C" mentioned above. 1-4 Besides specific examples of "alkylthio", it also includes penthioyl, 1,1-dimethylpropylthioyl, 1,2-dimethylpropylthioyl, 1-methylbutyrothioyl, 2-methylbutyrothioyl, 4-methylpentylthioyl, 3-methylpentylthioyl, 2-methylpentylthioyl, 1-methylpentylthioyl, hexylthioyl, etc.

[0126] “C 1-6 "Alkylene" refers to a straight-chain or branched divalent saturated hydrocarbon group having 1 to 6 carbon atoms. 1-6 "alkylene" is preferably "C" 1-4 "alkylene", and more preferably "C 1-3 Alkylene. "C" 1-3 Specific examples of "alkylene" include methylene, ethylene, and propylene. 1-4 Specific examples of "alkylene" include the "C" mentioned above. 1-3 Besides specific examples of "alkylene", it also includes butylene, 1,1-dimethylethylene, 1,2-dimethylethylene, 1-methyltrimethylene, 2-methyltrimethylene, etc. "C" 1-6 Specific examples of "alkylene" include the "C" mentioned above. 1-4 In addition to specific examples of "alkylene", it also includes pentylene, 1,1-dimethyltrimethylene, 1,2-dimethyltrimethylene, 1-methylbutylene, 2-methylbutylene, 1-methylpentylene, 2-methylpentylene, 3-methylpentylene, hexylene, etc.

[0127] “C 2-6 "Alkenyl" refers to a straight-chain or branched divalent unsaturated hydrocarbon group with 2 to 6 carbon atoms and containing 1 to 3 double bonds. 2-6 "Ideinyl" is preferred to be "C" 2-4 "Ideinyl". "C" 2-4Specific examples of "alkenyl" include vinylidene, vinylidene group, propenyl, methylpropenyl, and butenyl. 2-6 Specific examples of "alkenyl" include the "C" mentioned above. 2-4 In addition to specific examples of "alkenyl", it also includes pentenyl, hexenyl, etc.

[0128] “C 3-10 Alicyclic groups refer to cyclic saturated hydrocarbon groups with 3 to 10 carbon atoms, including some groups with unsaturated bonds and groups with cross-linked structures. 3-10 The "alicyclic group" is preferably "C". 3-7 Alicyclic group. "C" 3-7 Specific examples of "alicyclic groups" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. 3-10 Specific examples of "alicyclic groups" include the aforementioned "C" 3-7 In addition to specific examples of "alicyclic groups", it also includes cyclooctyl, cyclononyl, cyclodecyl, adamantyl, etc.

[0129] “C 3-10 "Alicyclic group" also includes the above-mentioned C 3-10 A group that has fused an alicyclic group with an aromatic ring to form a bicyclic structure. Specific examples of such fused compounds include structures represented by the following formula.

[0130] [Chemical Formula 13] Specific examples of the aforementioned cross-linked structures include structures represented by the following formula.

[0131] [Chemical Formula 14] “C 3-10 "Cycloalkylene" refers to a cyclic divalent saturated hydrocarbon group having 3 to 10 carbon atoms, including some groups with unsaturated bonds and groups with cross-linked structures. 3-10 "Cycloalkylene" is preferred. 3-7 "Cycloalkylene". 3-7 Specific examples of "cycloalkylene" include cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, and cycloheptylene. "C" 3-10 Specific examples of "cycloalkylene" include those mentioned above. 3-7 Besides specific examples of "cycloalkylene", it also includes cycloalkylene, cycloalkylene, cycloalkylene, adamantylene, etc.

[0132] Specific examples of the aforementioned cross-linked structures include structures represented by the following formula.

[0133] [Chemical Formula 15] “C 3-10 "Cycloolefin" refers to a cyclic divalent unsaturated hydrocarbon group having 3 to 10 carbon atoms, including groups with cross-linked structures. 3-10 Specific examples of "cyclohexene group" include cyclobutene group, cyclopentene group, cyclohexene group, etc.

[0134] "3- to 10-membered saturated carbon rings" refer to cyclic saturated hydrocarbons having 3 to 10 carbon atoms. "3- to 10-membered saturated carbon rings" are preferably "4- to 6-membered saturated carbon rings." Specific examples of "4- to 6-membered saturated carbon rings" include cyclobutane rings, cyclopentane rings, and cyclohexane rings. Specific examples of "3- to 10-membered saturated carbon rings," in addition to the aforementioned examples, also include cyclopropane rings, cycloheptane rings, cyclooctane, cyclononane, and cyclodecane.

[0135] "4- to 10-membered non-aryl heterocyclic groups" refer to monovalent non-aryl heterocyclic groups composed of 1 to 2 atoms independently selected from nitrogen, oxygen, and sulfur atoms and 2 to 9 carbon atoms, including groups with partially unsaturated bonds and groups with cross-linked structures. The atoms constituting the ring may include oxidized atoms such as -C(O)-, -S(O)-, or -SO2-. "4- to 10-membered non-aryl heterocyclic groups" are preferably "4- to 6-membered non-aryl heterocyclic groups." Specific examples of "4- or 5-membered non-aryl heterocyclic groups" include oxoheterocyclic butyl, azathiocyclic butyl, pyrrolidinyl, imidazoalkyl, oxazolidinyl, thiazoalkyl, oxoimidazoalkyl, dioxazolidinyl, oxoxazolidinyl, dioxoxazolidinyl, dioxathiazoalkyl, tetrahydrofuranyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, tetrahydropyranyl, etc. Examples of “4- to 10-membered non-aryl heterocyclic groups” include, in addition to the specific examples of “4- to 6-membered monocyclic non-aryl heterocyclic groups” mentioned above, aziridine heptyl groups, etc. As used herein, “aziridine butyl” and the like refer to divalent groups derived from “aziridine butyl” and the like.

[0136] "4- to 10-membered non-aryl heterocyclic groups" also encompasses groups that form bicyclic structures by fusion of 4- to 10-membered non-aryl heterocyclic groups with a 6-membered aromatic ring or a 6-membered aromatic heterocycle. Examples of 6-membered aromatic rings used to form fused ring groups include benzene rings. Examples of 6-membered aromatic heterocycles used to form fused ring groups include pyridine, pyrimidine, pyridazine, etc. Specific examples of bicyclic "4- to 10-membered non-aryl heterocyclic groups" forming fused ring groups include dihydroindolyl, dihydroisoindolyl, dihydropurine, dihydrothiazopyrimidinyl, dihydrobenzodioxane, isoindolyl, indazole, tetrahydroquinolinyl, tetrahydroisoquinolinyl, tetrahydronaphthidyl, etc.

[0137] "4 to 10-membered divalent non-aryl heterocyclic groups" refer to divalent non-aryl heterocyclic groups composed of 1 to 2 atoms independently selected from nitrogen, oxygen, and sulfur atoms and 2 to 9 carbon atoms, including groups with partially unsaturated bonds and groups with cross-linked structures. The atoms constituting the ring may include oxidized atoms such as -C(O)-, -S(O)-, or -SO2-. "4 to 10-membered divalent non-aryl heterocyclic groups" are preferably "4 to 6-membered divalent non-aryl heterocyclic groups". Specific examples of "4- to 6-membered divalent non-aryl heterocyclic groups" include oxetanylene, zazolylene, tetrahydrofurylene, pyrrolidinylene, imidazolidinylene, piperidinylene, molpholinylene, thiomolpholinylene, dioxothiomolpholinylene, and hexamethylimino. Examples of "4- to 10-membered divalent non-aryl heterocyclic groups" include eniminylene, oxazolidinylene, thiazolidinylene, oxoimidazolidinylene, dioxoimidazolidinylene, oxooxazolidinylene, dioxooxazolidinylene, dioxothiazolidinylene, tetrahydrofuranyl, and tetrahydropyranylene. In addition to the specific examples of "4- to 6-membered divalent non-aryl heterocyclic groups" mentioned above, examples of "4- to 10-membered divalent non-aryl heterocyclic groups" also include azepanylene.

[0138] "4- to 10-membered divalent non-aryl heterocyclic groups" also encompasses groups that form bicyclic structures by fusion of 4- to 10-membered divalent non-aryl heterocyclic groups with a 6-membered aromatic ring or a 6-membered aromatic heterocycle. Examples of 6-membered aromatic rings used to form fused ring groups include benzene rings. Examples of 6-membered aromatic heterocycles used to form fused ring groups include pyridine, pyrimidine, and pyridazine. Specific examples of bicyclic "4 to 10-membered divalent non-aryl heterocyclic groups" that form fused ring groups include dihydroindolylene, dihydroisoindolylene, dihydropurinylene, dihydrothiazolopyrimidinylene, dihydrobenzodioxanylene, isoindolylene, indazolylene, tetrahydroquinolylene, tetrahydroisoquinolylene, and tetrahydronaphthyridinylene.

[0139] “C 6-10 "Aryl" refers to an aromatic cyclic group having 6 to 10 carbon atoms. 6-10 Specific examples of "aryl" include phenyl, 1-naphthyl, 2-naphthyl, etc. Preferred examples include phenyl.

[0140] “C 6-10 "Aryl" also includes C 6-10 Aryl and C 4-6 A group consisting of an alicyclic group or a bicyclic structure formed by the fusion of a 5- to 6-membered non-aryl heterocyclic group. The bicyclic "C" that forms the fused ring group. 6-10 Specific examples of "aryl" include groups represented by the following formula.

[0141] [Chemical Formula 16] "Aromatic ring" refers to the aforementioned "C" 6-10 The ring portion of "aryl".

[0142] "5- to 10-membered heteroaryl" refers to a cyclic group derived from a monocyclic 5- to 7-membered aromatic heterocycle, each containing 1 to 4 atoms independently selected from nitrogen, oxygen, and sulfur atoms, or a cyclic group derived from a bicyclic 8- to 10-membered aromatic heterocycle. It is preferably a "5- to 7-membered monocyclic heteroaryl," more preferably pyridyl, pyrimidinyl, quinolinyl, or isoquinolinyl, and even more preferably pyridyl. Specific examples of "5- to 7-membered monocyclic heteroaryl" include pyridyl, pyridazinyl, isothiazolyl, pyrroleyl, furanyl, thiopheneyl, thiazolyl, imidazoleyl, pyrimidinyl, thiadiazolyl, pyrazolyl, oxazolyl, isoxazolyl, pyrazinyl, triazinyl, triazolyl, oxadiazolyl, triazolyl, tetrazolyl, etc. In addition to the specific examples of "5- to 7-membered monocyclic heteroaryl groups" mentioned above, specific examples of "5- to 12-membered heteroaryl groups" also include indole, inzolyl, chromenyl, quinolinyl, isoquinolinyl, benzofuranyl, benzothiophenyl, benzooxazolyl, benzothiazolyl, benzoisooxazolyl, benzoisothiazolyl, benzotriazolyl, and benzimidazolyl.

[0143] "Aromatic heterocyclic rings" refer to the ring portion of the aforementioned "5 to 12-membered heteroaryl groups".

[0144] "3- to 10-membered cycloalkanes" refer to cyclic saturated hydrocarbons with 3 to 10 carbon atoms, including some groups with unsaturated bonds and groups with cross-linked structures, and some of them can be fused with another ring. Specific examples of "3- to 10-membered cycloalkanes" include cyclobutane, cyclopentane, cyclohexane, cycloheptane, etc.

[0145] "6- to 10-membered aromatic rings" refer to cyclic aromatic hydrocarbons having 6 to 10 carbon atoms, and a portion of these rings can fused with another ring. Specific examples of "6- to 10-membered aromatic rings" include benzene rings, naphthalene, etc.

[0146] "5- to 10-enriched aromatic heterocycles" refer to monocyclic 4- to 7-enriched aromatic heterocycles or bicyclic 8- to 12-enriched aromatic heterocycles, each containing 1 to 4 atoms independently selected from nitrogen, oxygen, and sulfur atoms, and a portion of which may be fused with another ring. Preferably, they are "5- to 6-enriched aromatic heterocycles," "5-enriched aromatic heterocycles," or "6-enriched aromatic heterocycles." Specific examples of "5- to 6-enriched aromatic heterocycles" include furans, thiophenes, oxazoles, pyrazoles, pyridines, pyrazines, pyrimidines, and pyridazines. Specific examples of "5-enriched aromatic heterocycles" include pyrazoles, furans, thiophenes, and oxazoles. Specific examples of "6-enriched aromatic heterocycles" include pyridines, pyrazines, pyrimidines, and pyridazines.

[0147] "6- to 10-membered divalent aromatic ring groups" refers to monocyclic and bicyclic divalent aromatic ring groups having 6 to 10 carbon atoms. "6- to 10-membered divalent aromatic ring groups" are preferably "6-membered divalent aromatic ring groups". Specific examples of "6- to 10-membered divalent aromatic ring groups" and "6-membered divalent aromatic ring groups" include divalent benzene rings.

[0148] "5- to 10-membered divalent aromatic heterocyclic groups" refer to divalent cyclic groups derived from monocyclic 5- to 7-membered aromatic heterocycles, each containing 1 to 4 atoms independently selected from nitrogen, oxygen, and sulfur atoms, or divalent cyclic groups derived from bicyclic 8- to 10-membered aromatic heterocycles. Preferably, they are "5- to 6-membered divalent aromatic heterocyclic groups," more preferably "5-membered divalent aromatic heterocyclic groups." Specific examples of "5-membered divalent aromatic heterocyclic groups" include divalent pyrazoles, divalent furans, divalent thiophenes, and divalent oxazoles. In addition to the specific examples of "5-membered divalent aromatic heterocyclic groups" mentioned above, examples of "5- to 10-membered divalent aromatic heterocyclic groups" and "5- to 6-membered divalent aromatic heterocyclic groups" also include divalent pyridines, divalent pyrimidines, divalent pyrazines, and divalent pyridazines.

[0149] "Cancer" refers to malignant tumors and encompasses carcinomas, sarcomas, and hematologic malignancies. Specific examples of "cancer" include acoustic neuroma, acute leukemia, acute lymphoblastic leukemia, acute myeloid leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic, and promyelocytic), acute T-cell leukemia, basal cell carcinoma, gallbladder / choleduct cancer, bladder cancer, brain cancer, breast cancer, bronchial cancer, cervical cancer, chondrosarcoma, choriocarcinoma, chorioepithelial carcinoma, urothelial carcinoma, chronic leukemia, chronic lymphocytic leukemia, chronic myeloid (granulocytic) leukemia, and chronic myeloid leukemia. Leukemia, colorectal cancer, cystic adenocarcinoma, diffuse large B-cell lymphoma, proliferative dysplasia (developmental abnormalities and metaplasia), embryonal carcinoma, endometrial cancer, epithelioid sarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen receptor-positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer. Cancer), glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, hepatocellular carcinoma, hormone-independent prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphangiosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignant tumors and hyperproliferative disorders of the bladder, breast, colon, lung, ovary, pancreas, prostate, skin and uterus, malignant tumors of the lymphatic system of T-cell or B-cell origin, leukemia, lymphoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, multiple lesions Myeloma, myeloid leukemia, myeloma, myxosarcoma, neuroblastoma, midline NUT carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillary gland carcinoma, papillary carcinoma, pineal tumor, polycythemia vera, prostate cancer, rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung cancer, gastric cancer, squamous cell carcinoma, synovial tumor, sweat gland carcinoma, thyroid cancer, Waldenström macroglobulinemia, testicular tumor, uterine cancer, Wilms' tumor.Tumors, including malignant rhabdoid tumors, epithelioid sarcomas, atypical teratomas / rhabdoid tumors, schwannomas, chordal meningiomas, neuroepithelial tumors, glial neuron tumors, craniopharyngiomas, glioblastomas, chordomas, myoepithelial tumors, extraosseous myxoid chondrosarcomas, synovial sarcomas, ossifying fibromyxoid tumors, basal squamous cell carcinoma of the nasal cavity, esophageal adenocarcinoma, papillary thyroid carcinoma, follicular thyroid carcinoma, gastrointestinal stromal tumors, undifferentiated rhabdoid tumors of the pancreas, rhabdoid tumors of the digestive system, renal medullary carcinoma, endometrial cancer, myoepithelioma-like tumors in the female vulvar region, colon cancer, and mesotheliomas.

[0150] In this article, "CBP" and "P300" both refer to histone acetyltransferases involved in chromatin regulation and are paralogous to each other. "CBP / P300" refers to "CBP" and "P300". Histone acetyltransferases are enzymes that primarily (but not limited to) transfer acetyl groups to lysine residues located at the amino-terminal tail of histones. CBP and P300 primarily (but not limited to) acetylate histone H2A, H2B, H3, or H4. In particular, histone H3 primarily (but not limited to) acetylates lysine 18, lysine 27, lysine 56, and lysine 122 (H3K18, H3K27, H3K56, and H3K122, respectively). In particular, the acetylation of histone H3K27 is known to be a marker of open chromatin and plays a key role in gene expression regulation (J Hum Genet. 2013 July; 58(7): 439-45). p53 (Cell. Aug. 1997; 90(4): 595-606), MyoD (J Biol Chem. Nov. 2000; 275(44): 34359-34364), STAT3 (Science. Jan. 2005; 307(5707): 269-273), and androgen receptor (J Biol Chem. July 2000; 275(27):20853-20860) have been reported as substrates other than histones. When referred to herein as “CBP” and “P300”, they generally refer to proteins, but may also refer to the nucleic acids encoding them or, depending on the context, genes as a concept. Those skilled in the art will understand the terminology appropriately from the context.

[0151] Important functional domains of CBP and P300 include the HAT domain, the bromodomain (BRD), the CH1 / CH2 / CH3 domain (a cysteine-histidine rich domain), and the KIX domain (Mol Genet Metab. 2016. 119 (1-2):37-43). The HAT domain is primarily (but not limited to) the domain that transfers acetyl groups to lysine residues located at the N-terminal tail of histones. The bromodomain is primarily (but not limited to) the protein domain that recognizes N-acetylated lysine residues found at the N-terminal tail of histones.

[0152] As used herein, the term “CBP” refers to any naturally occurring CBP derived from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats) unless otherwise stated. The term encompasses both unprocessed CBP and any form of CBP produced through cellular processing. The term also encompasses naturally occurring CBP variants such as splice variants and allelic variants. Human CBP is registered with UniProt accession number: Q92793. The representative amino acid sequence of human CBP is described in UniProt Q92793-1 (SEQ ID NO: 1) and UniProt Q92793-2 (SEQ ID NO: 2).

[0153] As used herein, the term "P300" refers to any naturally occurring P300 derived from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats) unless otherwise stated. The term encompasses both unprocessed P300 and any form of P300 produced through cellular processing. The term also encompasses naturally occurring P300 variants such as splice variants and allelic variants. Human P300 is registered with UniProt accession number: Q09472. The representative amino acid sequence of human P300 is described in UniProt Q09472-1 (SEQ ID NO: 3).

[0154] A “CBP / P300 inhibitor” is a substance that inactivates CBP and / or P300, reduces their activity, and / or decreases their expression. “Decreased CBP / P300 expression” can occur at any stage, such as the pre-transcriptional level (e.g., genomic stage), transcriptional level, post-transcriptional regulatory level, translational level, or post-translational modification level. A “CBP / P300 inhibitor” is preferably a HAT inhibitor or a BRD inhibitor, and more preferably a HAT inhibitor.

[0155] "HAT inhibitors" are compounds that inhibit the activity of histone acetyltransferases (HATs) at CBP and / or P300. For example, they can be detected by fluorescence detection of CoA-SH, a byproduct generated in the histone acetyltransferase reaction (e.g., Gao T. et al., Methods Mol Biol. 2013; 981: 229-38), by detection using radioisotopes (e.g., Lau OD et al., J Biol Chem. 2000; 275(29): 21953-9), by detection of acetylated histone peptides using TR-FRET (e.g., PerkinElmer, LANCE Ultra, or AlphaLISA products), and by detection using NADH (e.g., Berndsen et al., Methods. 2005; 36(4): 32). 1-3 1) These are used to detect histone acetyltransferase activity. Examples of HAT inhibitors include compounds disclosed in WO 2016 / 044770, WO 2016 / 044771, WO 2016 / 044777, WO 2018 / 235966, WO 2019 / 111980, WO 2019 / 049061, WO 2019 / 161162, WO 2019 / 161157, WO 2019 / 201291 and WO 2020 / 108500.

[0156] "BRD inhibitors" are compounds that inhibit the function of the bromine domain (BRD) of CBP and / or P300. For example, the function of the bromine domain can be detected by methods such as TR-FRET, which detects the binding between the bromine domain and acetylated lysine residues (e.g., Acta Pharmacol Sin. 2020; 41(2): 286-292). Examples of BRD inhibitors include compounds disclosed in WO 2017 / 205538, WO 2016 / 086200, WO 2018 / 073586, WO 2019 / 055877, WO 2017 / 140728, WO 2019 / 191667, and WO 2019 / 195846.

[0157] Histone acetyltransferase (HAT) activity is the enzymatic activity that transfers acetyl groups to lysine residues of substrate proteins. Examples of substrates include histones and p53.

[0158] The bromine domain is a protein domain that recognizes N-acetylated lysine residues. N-acetylated lysine residues are found, for example, on the amino-terminal tail of histones.

[0159] In the compounds of this disclosure represented by formulas (1), (2), (3), (4), (5), (6), (7), (8), (9), or (10), preferred A, B, and R are... 1 R 2a R 2b R 3 R 4 R 5 R6, R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9a R 9b The compounds listed below are a, b, ring Q, and Z, but the scope of this disclosure is not limited to the range of compounds listed below.

[0160] A preferred embodiment of A includes CHF and CH2.

[0161] A more preferred embodiment of A includes CHF.

[0162] Other preferred embodiments of A include CH2.

[0163] The preferred implementation of B includes the following formula (B-1).

[0164] [Chemical Formula 17] in This indicates the binding position with the nitrogen atom on the hydantoin ring.

[0165] More preferred embodiments of B include the following formulas (B-2), (B-3), and (B-4).

[0166] [Chemical Formula 18] in This indicates the binding position with the nitrogen atom on the hydantoin ring.

[0167] R 1 The preferred implementation scheme includes C 1-6 Alkyl and C 3-10 Alicyclic group (the alkyl or alicyclic group may optionally be substituted by 1 to 3 identical or different halogen atoms).

[0168] R 1 A more preferred embodiment includes C 1-6 Alkyl and C 3-10 Alicyclic group (the alkyl or alicyclic group is optionally substituted with 1 to 3 fluorine atoms).

[0169] R 1 A further preferred embodiment includes C atoms optionally substituted with 1 to 3 fluorine atoms. 1-3 alkyl.

[0170] R 1 Another preferred implementation scheme includes CF3.

[0171] R 2a and R 2b Each preferred embodiment independently includes a C that is optionally substituted with one to three identical or different halogen atoms. 1-6 alkyl.

[0172] R 2a and R 2b Other preferred embodiments include R 2a and R 2b Together with the carbon atoms they are attached to, they form C 3-6 Embodiments of a cycloalkylene group or a 4- to 6-membered divalent nonaryl heterocyclic group (the cycloalkylene group or divalent nonaryl heterocyclic group may optionally be substituted by 1 to 3 identical or different halogen atoms).

[0173] R 2a and R 2b The most preferred implementation scheme includes R 2a and R 2b Together with the carbon atoms they are attached to, they form C 3-6 Embodiments of a cycloalkylene group or a 4- to 6-membered divalent nonaryl heterocyclic group (the cycloalkylene group or divalent nonaryl heterocyclic group may optionally be substituted with 1 to 3 fluorine atoms).

[0174] R 3 The preferred implementation scheme includes C 6-10 Aryl, 5- to 10-membered heteroaryl, C 3-10 Alicyclic groups and 4 to 10-membered non-aryl heterocyclic groups (the aryl, heteroaryl, alicyclic, or non-aryl heterocyclic groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0175] R 3 A more preferred embodiment includes C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents) and 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0176] R3 A further preferred embodiment includes C 6-10 aryl and 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from fluorine and C) 1-6 Alkyl substituents).

[0177] R 3 Another, even more preferred embodiment includes 4-fluorophenyl, 4-(trifluoromethyl)phenyl and 4-fluoro-2-pyridyl, and a more preferred embodiment includes 4-fluorophenyl and 4-fluoro-2-pyridyl.

[0178] R 3 The most preferred embodiment includes 4-fluorophenyl.

[0179] R 3 Other preferred embodiments include 4-fluoro-2-pyridyl.

[0180] R 4 Preferred implementation schemes include single bonds, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents) and 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0181] R 4 A more preferred embodiment includes a single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents) and 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0182] R 4 A further preferred embodiment includes a single bond, C 1-6 Alkylene groups and 4- to 6-membered divalent non-aryl heterocyclic groups.

[0183] R 4 Another, even better, implementation includes a single bond.

[0184] R 4 Another, even better, implementation scheme includes C 1-6 Alkylene.

[0185] R 4 Another, even more preferred embodiment includes 4 to 6-membered divalent nonaryl heterocyclic groups.

[0186] R 4 The most preferred embodiment includes nitrous heterocyclic butyl.

[0187] R 4 Other preferred embodiments include methylene.

[0188] R 5 Preferred embodiments include hydrogen atoms, halogen atoms, hydroxyl groups, cyano groups, and -NR groups. 7b R 7c -SO2R 7d -CONR 7e R 7f C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12Substituents), 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents) and 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0189] R 5 A more preferred embodiment includes hydrogen atoms, halogen atoms, hydroxyl groups, cyano groups, and C atoms. 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents) and 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0190] R 5 A further preferred embodiment includes cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents) and 4 to 6-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0191] R 5 Another, even better, implementation scheme includes C 1-6 Alkyl groups and 4 to 6-membered non-aryl heterocyclic groups.

[0192] R 5 The most preferred embodiment includes a methyl group and an oxetine.

[0193] R 6 The preferred embodiment includes hydrogen atoms and fluorine atoms.

[0194] R 6 A more preferred embodiment includes hydrogen atoms.

[0195] R 7aR 7b R 7c R 7d R 7e and R 7f The preferred embodiments each independently include hydrogen atoms and C atoms. 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0196] R 7a R 7b R 7c R 7d R 7e and R 7f More preferred embodiments each independently include a hydrogen atom and a methyl group.

[0197] R 8 The preferred embodiment includes hydrogen atoms and C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0198] R 8 A more preferred embodiment includes C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0199] R 8 A further preferred embodiment includes a methyl group.

[0200] R 9a and R 9b The preferred embodiments each independently include hydrogen atoms, halogen atoms, and C atoms. 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0201] R 9a and R 9b More preferred embodiments each independently include halogen atoms.

[0202] R 9a and R 9b A further preferred embodiment includes fluorine atoms.

[0203] R 10 The preferred implementation scheme includes C 1-6 alkyl.

[0204] R 11 and R 12The preferred embodiments each independently include hydrogen atoms and C atoms. 1-6 alkyl.

[0205] R 11 and R 12 Other preferred embodiments include R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 In the case of alkyl groups, embodiments are implemented in which 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups are formed together with the nitrogen atoms to which they are attached.

[0206] R 11 and R 12 A more preferred embodiment includes a methyl group.

[0207] Preferred embodiments of ring Q include a 6- to 10-membered aromatic ring (the aromatic ring is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0208] A more preferred embodiment of ring Q includes a benzene ring (the benzene ring is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

[0209] A further preferred embodiment of ring Q includes a benzene ring.

[0210] Preferred embodiments of Z include -O-, 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents) and 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0211] A more preferred embodiment of Z includes a 4- to 10-membered divalent nonaryl heterocyclic group (the divalent nonaryl heterocyclic group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12Substituents) and 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0212] A further preferred embodiment of Z includes a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

[0213] Another preferred embodiment of Z includes a divalent pyrazolyl group.

[0214] Preferred implementations of a include 0, 1, and 2.

[0215] More preferred embodiments of a include 1 and 2.

[0216] A further preferred embodiment of a includes 1.

[0217] Preferred implementation schemes for b include 1 and 2.

[0218] A more preferred embodiment of b includes 1.

[0219] A more preferred embodiment of a and b includes an embodiment where both are 1.

[0220] An embodiment of the compound represented by formula (1) includes the following (A).

[0221] (A) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF or CH2. B is the following formula (B-1): [Chemical Formula 19] in Indicates the bonding position with the nitrogen atom on the hydantoin ring. Ring Q is a 6- to 10-membered aromatic ring (the aromatic ring is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents), Z is a -O-, 6 to 10-membered divalent aromatic ring group (the divalent aromatic ring group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12Substituents), 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 1 C is optionally substituted with 1 to 3 fluorine atoms 1-3 alkyl, R 2a and R 2b Together with the carbon atoms they are attached to, they form C 3-6 Cycloalkyl or 4 to 6-membered divalent nonaryl heterocyclic groups (the cycloalkyl or divalent nonaryl heterocyclic groups may optionally be substituted with 1 to 3 fluorine atoms). R 3 C 6-10 Aryl (the aryl group is optionally replaced by 1 to 3 identical or different C atoms selected from halogen atoms and optionally substituted C atoms) 1-6 Alkyl substituents) or 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents), R 4 For single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents) or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 Hydrogen atom, halogen atom, hydroxyl group, cyano group, -NR 7b R 7c -SO2R 7d -CONR 7e R 7f C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 7b R 7c R 7d R 7e and R 7f Each is independently a hydrogen atom or a carbon atom. 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0222] An embodiment of the compound represented by formula (1) includes the following (B).

[0223] (B) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF or CH2. B is one of the following formulas: (B-2), (B-3), or (B-4): [Chemical Formula 20] in Indicates the bonding position with the nitrogen atom on the hydantoin ring. a is 0, 1, or 2. b is 1 or 2. R 8 It is a hydrogen atom or a carbon atom. 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 9a and R 9b Each can be independently a hydrogen atom, a halogen atom, or a carbon atom. 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), Ring Q is a 6- to 10-membered aromatic ring (the aromatic ring is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents), Z is a -O-, 5 to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 1 For CF3, R 3 It is 4-fluorophenyl, 4-(trifluoromethyl)phenyl, or 4-fluoro-2-pyridyl. R 4 For single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents) or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 Hydrogen atom, halogen atom, hydroxyl group, cyano group, -NR 7b R 7c -SO2R 7d -CONR 7e R 7f C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 Substituents), C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 Substituents), C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR11 R 12 Substituents), 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 7b R 7c R 7d R 7e and R 7f Each is independently a hydrogen atom or a carbon atom. 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0224] An embodiment of the compound represented by formula (2) includes the following (C).

[0225] (C) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF or CH2. R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. Z is 4 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C1-6 Alkyl and -NR 11 R 12 (substituents) R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 for C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 It consists of hydrogen atoms or halogen atoms, and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0226] An embodiment of the compound represented by formula (2) includes the following (D).

[0227] (D) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF. Z is 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 for C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 It is a hydrogen atom, and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0228] An embodiment of the compound represented by formula (3) includes the following (E).

[0229] (E) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 for C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0230] An embodiment of the compound represented by formula (3) includes the following (F).

[0231] (F) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a 4- to 6-membered divalent non-aryl heterocyclic group, and R 5 for C 1-3 alkyl, or 4 to 6-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

[0232] An embodiment of the compound represented by formula (3) includes the following (G).

[0233] (G) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a nitrosobutyryl or piperidinyl group, and R 5 It is an oxocyclic butyl group.

[0234] An embodiment of the compound represented by formula (4) includes the following (H).

[0235] (H) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a nitrosobutane, and R 5 It is an oxocyclic butyl group.

[0236] An embodiment of the compound represented by formula (5) includes the following (I).

[0237] (I) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF or CH2. Z is 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 5 for hydrogen atom, hydroxyl group Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 It consists of hydrogen atoms or halogen atoms. R 8 C 1-6 Alkyl, and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0238] An embodiment of the compound represented by formula (5) includes the following (J).

[0239] (J) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF. Z is 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 for Single key, or C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 5 for hydroxyl group Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic groups (the alicyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6Alkyl and -NR 11 R 12 (substituents) R 6 It is a hydrogen atom. R 8 It is a methyl group, and R 11 and R 12 Each is independently a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 When both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

[0240] An embodiment of the compound represented by formula (6) includes the following (K).

[0241] (K) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 for Single key, or C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 5 for hydroxyl group Cyano, C 1-6 alkyl, C 3-10 Alicyclic groups, or 4 to 10-membered non-aryl heterocyclic groups.

[0242] An embodiment of the compound represented by formula (6) includes the following (L).

[0243] (L) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 for Single key, or C1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 5 for methyl group, or Oxyhexacyclic butyl group.

[0244] An embodiment of the compound represented by formula (6) includes the following (M).

[0245] (M) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a single bond, and R 5 It is a methyl group.

[0246] An embodiment of the compound represented by formula (7) includes the following (N).

[0247] (N) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a single bond, and R 5 It is a methyl group.

[0248] An embodiment of the compound represented by formula (8) includes the following (O).

[0249] (O) A compound or a pharmaceutically acceptable salt thereof, wherein A is CHF or CH2. Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms, C... 1-6 Alkyl and -NR 11 R 12 (substituents) R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5It is a 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 It consists of hydrogen atoms or halogen atoms, and R 9a and R 9b It is a fluorine atom.

[0250] An embodiment of the compound represented by formula (9) includes the following (P).

[0251] (P) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a 4- to 6-membered divalent non-aryl heterocyclic group, and R 5 It is a 4- to 6-membered non-aryl heterocyclic group.

[0252] An embodiment of the compound represented by formula (9) includes the following (Q).

[0253] (Q) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a nitrosobutane, and R 5 It is an oxocyclic butyl group.

[0254] An embodiment of the compound represented by formula (10) includes the following (R).

[0255] (R) A compound or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a 4- to 6-membered divalent non-aryl heterocyclic group, and R 5 It is a 4- to 6-membered non-aryl heterocyclic group.

[0256] An embodiment of the compound represented by formula (10) includes the following (S).

[0257] (S) A compound or a pharmaceutically acceptable salt thereof, wherein R 3It is 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 It is a nitrosobutane, and R 5 It is an oxocyclic butyl group.

[0258] The compounds disclosed herein can be administered orally, parenterally, or rectally, and the daily dose may vary depending on the type of compound, the method of administration, the patient's symptoms, and age. For example, in the case of oral administration, the dosage can usually be from about 0.01 to 1000 mg per kilogram of body weight, more preferably from about 0.1 to 500 mg, in divided doses, once or multiple times, for humans or mammals. In the case of parenterial administration, such as intravenous injection, the dosage can usually be from about 0.01 mg to 300 mg per kilogram of body weight, more preferably from about 1 mg to 100 mg, for humans or mammals. Administration regimens may include, for example, a single dose, once daily for three consecutive days, or twice daily for one week. Furthermore, the above methods of administration can be repeated at intervals of about 1 day to about 60 days.

[0259] The compounds disclosed herein can be administered parenterally or orally, directly or by using appropriate dosage forms. Examples of dosage forms include, but are not limited to, tablets, capsules, powders, granules, liquids, suspensions, injections, patches, poultices, etc. The formulations are prepared using pharmaceutically acceptable additives by known methods. Depending on the purpose, the additives may be excipients, disintegrants, binders, glidants, lubricants, coating agents, solvents, solubilizers, thickeners, dispersants, stabilizers, sweeteners, flavors, etc. Specific examples of additives include lactose, mannitol, crystalline cellulose, low-substituted hydroxypropyl cellulose, corn starch, partially pregelatinized starch, calcium carboxymethyl cellulose, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, magnesium stearate, sodium stearate fumarate, polyethylene glycol, propylene glycol, titanium dioxide, talc, etc.

[0260] The following describes by way of example the preparation methods of the compounds of this disclosure represented by formulas (1)-(10), but the preparation methods of the compounds of this disclosure are not limited thereto. The compounds used in the following preparation methods may form salts as long as they do not adversely affect the reaction.

[0261] The compounds disclosed herein can be prepared from known compounds as starting materials by means of, for example, the preparation methods described below A, B, C or D, or similar methods, or by appropriate combination with synthetic methods known to those skilled in the art.

[0262] Preparation method A Compounds (1-11) (which are compounds represented by formula (1), where A is CHF and Q is a benzene ring) can be prepared by, for example, the following preparation methods.

[0263] [Chemical Formula 21] Where R 1 R 2a R 2b R 3 R 4 R 5 And Z is as defined in [Item 1] above, and R 6 As defined in [Item 16] above.

[0264] Step 1-1: Preparation method of compounds (1-3) Compounds (1-3) can be prepared by reacting compound (1-1) with compound (1-2) in an inert solvent in the presence of a reducing agent.

[0265] Examples of reducing agents include sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride.

[0266] Examples of inert solvents include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; acetonitrile, acetone, methyl ethyl ketone, dimethylformamide, and N-methyl-2-pyrrolidone.

[0267] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 0°C to 25°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0268] Step 1-2: Preparation method of compounds (1-5) Compounds (1-5) can be prepared by subjecting compounds (1-3) and (1-4) to an amidation reaction in an inert solvent in the presence of a base.

[0269] Examples of bases include inorganic bases such as potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide.

[0270] Examples of inert solvents include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0271] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 25°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0272] Steps 1-3: Preparation methods of compounds (1-6) Compounds (1-6) can be prepared by deprotecting the benzyl group of compounds (1-5). For example, catalytic reduction using metal catalysts such as palladium / carbon, palladium hydroxide / carbon, etc., under a hydrogen atmosphere.

[0273] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 100°C, preferably from 0°C to 25°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0274] Steps 1-4: Preparation method of compounds (1-8) Compounds (1-8) can be prepared by reacting compounds (1-7) with a reducing agent. Compounds (1-7) can be synthesized by the method described in WO2016 / 044770.

[0275] Examples of reducing agents include sodium borohydride, sodium triacetoxyborohydride, and sodium cyanoborohydride.

[0276] There are no particular restrictions on the reaction temperature, but it is usually selected from -78°C to 150°C, preferably from -78°C to 25°C. The reaction time is usually from 30 minutes to 72 hours, preferably from 30 minutes to 24 hours.

[0277] Steps 1-5: Preparation methods of compounds (1-9) Compounds (1-9) can be prepared by reacting compounds (1-8) with a fluorinating agent in an inert solvent.

[0278] Examples of inert solvents include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0279] Examples of fluorinating agents include (diethylamino)sulfur trifluoride, FLUOLEAD TM wait.

[0280] There are no particular restrictions on the reaction temperature, but it is usually selected from -78°C to 150°C, preferably from -78°C to 25°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0281] Steps 1-6: Preparation method of compounds (1-10) Compounds (1-10) can be prepared by subjecting compounds (1-9) and (1-6) to photo-extending reaction in an inert solvent in the presence of a Mitsunobu reagent.

[0282] Examples of inert solvents include aromatic hydrocarbons such as toluene; and ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane.

[0283] Examples of photoelongation reagents include diethyl azodicarbonate (DEAD), diisopropyl azodicarbonate (DIAD), bis(2-methoxyethyl) azodicarbonate, or combinations of N,N,N',N'-tetramethylazodicarbonamide with triphenylphosphine or tributylphosphine. Cyanomethylenetrimethylphosphine (Tsunoda reagent) can also be used.

[0284] There are no particular restrictions on the reaction temperature, but it is usually selected from the range of 0°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0285] Steps 1-7: Preparation method of compound (1-11) Compounds (1-11) can be prepared by subjecting compounds (1-10) to palladium-catalyzed cross-coupling reactions with various coupling agents in an inert solvent.

[0286] Examples of inert solvents include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0287] Examples of palladium reagents include tetra(triphenylphosphine)palladium (0), bis(dibenzylpyridinylacetone)palladium (0), tri(dibenzylpyridinylacetone)dipalladium (0), bis(tri-tert-butylphosphine)palladium (0), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (II), etc.

[0288] Examples of bases include inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, and sodium hydroxide.

[0289] Examples of coupling reagents include boric acid bonded to Z and pinacol ester of borate bonded to Z.

[0290] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 25°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0291] Preparation method B Compounds (1-14) (which are compounds represented by formula (1), where Q is a benzene ring) can also be prepared by, for example, the following preparation methods.

[0292] [Chemical Formula 22] Among them, A and R 1 R 2a R 2b R 3 R 4 R 5 And Z as defined in [Item 1] above. R 6 As defined in [Item 16] above. W represents a halogen atom.

[0293] Step 2-1: Preparation method of compound (2-1) Compound (2-1) can be reacted in an inert solvent to form the compound ( 1-3 It is prepared by reacting with an amidating agent.

[0294] Examples of amidating agents include chloroacetyl chloride, bromoacetyl chloride, and chloroacetic anhydride.

[0295] Examples of inert solvents include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, N,N-dimethylpropylene urea, and pyridine.

[0296] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 25°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0297] Step 2-2: Preparation method of compound (1-13) Compounds (1-13) can be prepared by subjecting compounds (1-12) and (2-1) to alkylation in an inert solvent in the presence of a base.

[0298] Examples of inert solvents include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0299] Examples of bases include inorganic bases such as potassium carbonate and cesium carbonate; and metal alkoxides such as sodium methoxide and potassium tert-butoxide.

[0300] There are no particular restrictions on the reaction temperature, but it is usually selected from the range of 0°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0301] Steps 2-3: Preparation method of compound (1-14) Compounds (1-14) can be prepared by subjecting compounds (1-13) to palladium-catalyzed cross-coupling reactions with various coupling agents in an inert solvent.

[0302] Examples of inert solvents include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0303] Examples of palladium reagents include tetra(triphenylphosphine)palladium (0), bis(dibenzylpyridinylacetone)palladium (0), tri(dibenzylpyridinylacetone)dipalladium (0), bis(tri-tert-butylphosphine)palladium (0), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (II), etc.

[0304] Examples of bases include inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, and sodium hydroxide.

[0305] Examples of coupling reagents include boric acid bonded to Z and pinacol ester of borate bonded to Z.

[0306] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 25°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0307] Preparation method C Compounds (1-14) (which are compounds represented by formula (1), where Q is a benzene ring) can also be prepared by, for example, the following preparation methods.

[0308] [Chemical Formula 23] Among them, A and R 1 R 2a R 2b R 3 R 4 R 5 And Z as defined in [Item 1] above. R 6 As defined in [Item 16] above.

[0309] Step 3-1: Preparation method of compound (3-1) Compound (3-1) can be prepared by subjecting compound (1-12) to palladium-catalyzed cross-coupling reactions with various coupling agents in an inert solvent.

[0310] Examples of inert solvents include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0311] Examples of palladium reagents include tetra(triphenylphosphine)palladium (0), bis(dibenzylpyridinylacetone)palladium (0), tri(dibenzylpyridinylacetone)dipalladium (0), bis(tri-tert-butylphosphine)palladium (0), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (II), etc.

[0312] Examples of bases include inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, and sodium hydroxide.

[0313] Examples of coupling reagents include boric acid bonded to Z and pinacol ester of borate bonded to Z.

[0314] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 25°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0315] Step 3-2: Preparation method of compound (1-14) Compound (1-14) can be prepared by subjecting compound (3-1) and compound (1-6) to a photo-extending reaction in an inert solvent in the presence of a photo-extending reagent.

[0316] Examples of inert solvents include aromatic hydrocarbons such as toluene; and ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane.

[0317] Examples of photopolymerization reagents include diethyl azodicarbonate (DEAD), diisopropyl azodicarbonate (DIAD), bis(2-methoxyethyl) azodicarbonate, or combinations of N,N,N',N'-tetramethylazodicarbonamide with triphenylphosphine or tributylphosphine. Cyanomethylenetrimethylphosphine (Kakuda reagent) can also be used.

[0318] There are no particular restrictions on the reaction temperature, but it is usually selected from the range of 0°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0319] Preparation method D Compounds (1-14) (which are compounds represented by formula (1), where Q is a benzene ring) can also be prepared by, for example, the following preparation methods.

[0320] [Chemical Formula 24] Among them, A and R 1 R 2a R 2b R 3 R 4 R 5 And Z as defined in [Item 1] above. R 6 As defined in [Item 16] above. W represents a halogen atom.

[0321] Step 4-1: Preparation method of compound (1-14) Compounds (1-14) can be prepared by subjecting compounds (3-1) and (2-1) to alkylation in an inert solvent in the presence of a base.

[0322] Examples of inert solvents include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0323] Examples of bases include inorganic bases such as potassium carbonate and cesium carbonate; and metal alkoxides such as sodium methoxide and potassium tert-butoxide.

[0324] There are no particular restrictions on the reaction temperature, but it is usually selected from the range of 0°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0325] Preparation method E Compounds (1-17) (which are compounds represented by formula (1), where A is CH2 and Q is a benzene ring) can be prepared by, for example, the following preparation methods.

[0326] [Chemical Formula 25] Where R 1 R 2a R 2b R 3 R 4 R 5 And Z is as defined in [Item 1] above, and R 6 As defined in [Item 16] above.

[0327] Step 5-1: Preparation method of compound (1-16) Compounds (1-16) can be prepared by subjecting compounds (1-15) and (1-6) to a phototelephoto reaction in an inert solvent in the presence of a phototelephoto reagent. Compounds (1-15) can be synthesized by the method described in WO 2016 / 044770.

[0328] Examples of inert solvents include aromatic hydrocarbons such as toluene; and ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane.

[0329] Examples of photopolymerization reagents include diethyl azodicarbonate (DEAD), diisopropyl azodicarbonate (DIAD), bis(2-methoxyethyl) azodicarbonate, or combinations of N,N,N',N'-tetramethylazodicarbonamide with triphenylphosphine or tributylphosphine. Cyanomethylenetrimethylphosphine (Kakuda reagent) can also be used.

[0330] There are no particular restrictions on the reaction temperature, but it is usually selected from the range of 0°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0331] Step 5-2: Preparation method of compound (1-17) Compounds (1-17) can be prepared by subjecting compounds (1-16) to palladium-catalyzed cross-coupling reactions with various coupling agents in an inert solvent.

[0332] Examples of inert solvents include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidone, and N,N-dimethylpropylene urea.

[0333] Examples of palladium reagents include tetra(triphenylphosphine)palladium (0), bis(dibenzylpyridinylacetone)palladium (0), tri(dibenzylpyridinylacetone)dipalladium (0), bis(tri-tert-butylphosphine)palladium (0), [1,1'-bis(diphenylphosphine)ferrocene]palladium dichloride (II), etc.

[0334] Examples of bases include inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, and sodium hydroxide.

[0335] Examples of coupling reagents include boric acid bonded to Z and pinacol ester of borate bonded to Z.

[0336] There are no particular restrictions on the reaction temperature, but it is usually selected from 0°C to 150°C, preferably from 25°C to 100°C. The reaction time is usually from 1 hour to 72 hours, preferably from 1 hour to 24 hours.

[0337] In the above preparation methods, the starting raw materials and intermediates for which the preparation methods are not described can be obtained as commercial products, or can be synthesized from commercially available products by methods known to those skilled in the art or similar methods.

[0338] In each reaction of the above preparation methods, even if the use of a protecting group is not explicitly described, a protecting group may be used as needed. For example, if any functional group other than the reaction site changes under the described reaction conditions, or if the absence of a protecting group makes it unsuitable to carry out the described methods, the target compound can be obtained by protecting the portion other than the reaction site as needed and then deprotecting that portion after the reaction or a series of reactions is completed.

[0339] As protecting groups, those described in *Protective Groups in Organic Synthesis* (Theodora W. Greene, Peter GM Wuts, published by John Wiley & Sons, Inc., 1999), etc., can be used. Specific examples of amino protecting groups include benzyloxycarbonyl, tert-butyloxycarbonyl, acetyl, benzyl, etc. Specific examples of hydroxyl protecting groups include trialkylsilyl groups such as trimethylsilyl, tert-butyldimethylsilyl, etc., acetyl, benzyl, etc.

[0340] The introduction or removal of protecting groups can be carried out using methods commonly used in organic synthetic chemistry (see, for example, Protective Groups in Organic Synthesis above) or similar methods.

[0341] As used herein, protecting groups, condensing agents, etc., can be represented using the nomenclature of IUPAC-IUB (Biochemical Nomenclature Committees), which is commonly used in this field. It should be noted that the compound names used herein do not necessarily follow IUPAC nomenclature.

[0342] The intermediates or target compounds in the above preparation methods can also be introduced into another compound contained in this disclosure by appropriately transforming their functional groups (e.g., using amino, hydroxyl, carbonyl, halogen, etc., and protecting or deprotecting the functional groups as needed). The transformation of functional groups can be carried out by commonly used methods (see, for example, Comprehensive Organic Transformations, RC Larock, John Wiley & Sons Inc. (1999) etc.).

[0343] The intermediates or target compounds in the above preparation methods can be separated and purified using purification methods commonly used in organic synthesis chemistry (e.g., neutralization, filtration, extraction, washing, drying, concentration, recrystallization, and various chromatographic methods). The intermediates can also be used in subsequent reactions without any special purification.

[0344] As protecting groups, those described in *Protective Groups in Organic Synthesis* (Theodora W. Greene, Peter GM Wuts, published by John Wiley & Sons, Inc., 1999), etc., can be used. Specific examples of amino protecting groups include benzyloxycarbonyl, tert-butyloxycarbonyl, acetyl, benzyl, etc. Specific examples of hydroxyl protecting groups include trialkylsilyl groups such as trimethylsilyl, tert-butyldimethylsilyl, etc., acetyl, benzyl, etc.

[0345] The introduction or removal of protecting groups can be carried out using methods commonly used in organic synthetic chemistry (see, for example, Protective Groups in Organic Synthesis above) or similar methods.

[0346] As used herein, protecting groups, condensing agents, etc., can be represented using the nomenclature of IUPAC-IUB (Biochemical Nomenclature Committee), which is commonly used in this field. It should be noted that the compound names used herein do not necessarily follow IUPAC nomenclature.

[0347] The intermediates or target compounds in the above preparation methods can also be introduced into another compound contained in this disclosure by appropriately transforming their functional groups (e.g., using amino, hydroxyl, carbonyl, halogen, etc., and protecting or deprotecting the functional groups as needed). The transformation of functional groups can be carried out by commonly used methods (see, for example, Comprehensive Organic Transformations, RC Larock, John Wiley & Sons Inc. (1999) etc.).

[0348] The intermediates or target compounds in the above preparation methods can be separated and purified using purification methods commonly used in organic synthesis chemistry (e.g., neutralization, filtration, extraction, washing, drying, concentration, recrystallization, and various chromatographic methods). The intermediates can also be used in subsequent reactions without any special purification.

[0349] Examples of "pharmaceutically acceptable salts" include acid addition salts and base addition salts. Examples of acid addition salts include inorganic acid salts such as hydrochlorides, hydrobroms, sulfates, hydroiodides, nitrates, phosphates, etc., or organic acid salts such as citrates, oxalates, phthalates, fumarates, maleates, succinates, malates, acetates, formates, propionates, benzoates, trifluoroacetates, methanesulfonates, benzenesulfonates, p-toluenesulfonates, camphorsulfonates, etc. Examples of base addition salts include inorganic base salts such as sodium, potassium, calcium, magnesium, barium, and aluminum salts, or salts formed with organic bases such as trimethylamine, triethylamine, pyridine, methylpyridine, 2,6-dimethylpyridine, ethanolamine, diethanolamine, triethanolamine, tromethamine [tris(hydroxymethyl)methylamine], tert-butylamine, cyclohexylamine, dicyclohexylamine, and N,N-dibenzylethylamine. Examples of "pharmaceutically acceptable salts" also include amino acid salts formed with basic or acidic amino acids such as arginine, lysine, ornithine, aspartic acid, or glutamic acid.

[0350] Salts suitable for use as starting materials and intermediates, as well as acceptable salts used as raw materials in pharmaceuticals, are conventionally used non-toxic salts. Examples include acid addition salts such as organic acid salts (e.g., acetates, trifluoroacetates, maleates, fumarates, citrates, tartrates, methanesulfonates, benzenesulfonates, formates, toluenesulfonates, etc.) and inorganic acid salts (e.g., hydrochlorides, hydrobroms, hydroiodates, sulfates, nitrates, phosphates, etc.), salts formed with amino acids (e.g., arginine, aspartic acid, glutamic acid, etc.), metal salts such as alkali metal salts (e.g., sodium salts, potassium salts, etc.), alkaline earth metal salts (e.g., calcium salts, magnesium salts, etc.), ammonium salts, organic base salts (e.g., trimethylamine salts, triethylamine salts, pyridinium salts, methylpyridinium salts, dicyclohexylamine salts, N,N'-dibenzylethylenediamine salts, etc.). Those skilled in the art can appropriately select these salts.

[0351] The disclosed compound can be used with isotopes (e.g.) 2 H (or D), 3 H (or T) 11 C 13 C 14 C 13 N、 15 N、 15 O、 35 S, 18 F, 125 The compounds are replaced by I, etc., and these compounds are also covered by the compounds disclosed herein.

[0352] This disclosure covers compounds represented by formulas (1) to (7) and their pharmaceutically acceptable salts. The compounds of this disclosure may also be in the form of hydrates and / or solvates of various solvents (such as ethanol salts). Therefore, such hydrates and / or solvates are also covered by the compounds of this disclosure.

[0353] The disclosed compounds also cover all other possible isomers, such as optical isomers based on optically active centers, axially or planarly chiral isomers based on intramolecular rotational restriction, other stereoisomers, tautomers, geometric isomers, and any form of crystal form and mixture thereof.

[0354] Specifically, optical isomers and resisted isomers can be obtained as racemates, or in an optically active form if optically active starting materials or intermediates are used. If necessary, the corresponding racemates of raw materials, intermediates, or final products can be physically or chemically resolved into optical enantiomers during appropriate steps of the above-described preparation method using known separation methods such as the use of optically active columns or stepwise crystallization. Examples of resolution methods include diastereomeric methods, in which two types of diastereomeric isomers are synthesized by reacting the racemate with an optically active resolving agent, and then the diastereomeric isomers are resolved by methods such as stepwise crystallization, taking advantage of differences in their physical properties.

[0355] If a pharmaceutically acceptable salt of the compounds disclosed herein is required, when the compounds represented by formulas (1) to (10) are obtained as pharmaceutically acceptable salts, they may be directly purified; or when obtained in free form, the salt may be formed by dissolving or suspending the compounds in a suitable organic solvent and adding an acid or base according to common methods.

[0356] The disclosed compounds can be used in combination with another drug to enhance its effect. Specifically, the disclosed compounds can be used in combination with drugs such as hormone therapy agents, chemotherapy agents, immunotherapy agents, and agents that inhibit the action of cell growth factors and their receptors. In the following, drugs that can be used in combination with the disclosed compounds are simply referred to as the other drugs.

[0357] Although the disclosed compounds have shown excellent anticancer effects when used as a single agent, their effects can be further enhanced or patients' QOL can be improved by combining them with one or more of the other drugs mentioned above (combined use of multiple drugs).

[0358] Examples of "hormone therapy agents" include phosphostel, diethylstilbestrol, chlorestrol, medroxyprogesterone acetate, megestrol acetate, chlormedrone acetate, cyproterone acetate, danazol, dinogest, asoprisnil, allylestradiol, gestrinone, nomenoprogesterone, tadalafil, mepertricin, raloxifene, olmexifen, levomerocalcin, and anti-estrogens (such as tamoxifen citrate). citrate, toremifene citrate, pill formulations, mepitiostane, testosterone, aminoglutethimide, LH-RH derivatives (LH-RH agonists such as goserelin acetate, buserelin, leuprorelin, etc. and LH-RH antagonists), droloxifene, epixiostanol, ethinylestradiol sulfonate, aromatase inhibitors (such as falozole hydrochloride) Hydrochloride, anastrozole, letrozole, exemestane, vorozole, formestane, etc., anti-androgens (e.g., flutamide, enzalutamide, apalutamide, bicalutamide, nilumet, etc.), adrenocortical hormones (e.g., dexamethasone, prednisolone, betamethasone, triamcinolone, etc.), androgen synthesis inhibitors (e.g., abiraterone), retinoids, drugs that delay retinoid metabolism (e.g., riazol, etc.), etc.

[0359] For example, alkylating agents, antimetabolites, anticancer antibiotics, plant-derived anticancer agents, molecularly targeted therapeutic agents, immunomodulators, and other chemotherapeutic agents can be used as "chemotherapeutic agents." Representative examples are described below.

[0360] Examples of "alkylating agents" include nitrogen mustard, nitrogen mustard n-oxide hydrochloride, nitrogen mustard chlorate, cyclophosphamide, ifosfamide, thiotepa, carboquinone, inprofentoxin tosylate, busulfan, nimustine hydrochloride, dibromomannitol, melphalan, dacarbazine, ramustine, estradiol sodium phosphate, triethylmelamine, carmustine, lomustine, levozocin, piperobromethane, etoglucide, carboplatin, cisplatin, miplatin, nedaplatin, oxaliplatin, hexamethylmelamine, ambamustine, dibromospidium chloride, formustine, prednimustine, pumitepa, lipomustine, temozolomide, trefosinate, trefosinate, and zinostatin. Stimalamer, Adolaxine, Cysemustine, Bifelixine, Trabectin, and their DDS formulations, etc.

[0361] Examples of "antimetabolites" include mercaptopurine, 6-mercaptopurine riboside, thioinosine, methotrexate, pemetrexed, enoxabin, cytarabine, cytarabine ocfosfate, ancitabine hydrochloride, 5-FU agents (such as fluorouracil, tegafur, UFT, deoxyfluorouridine, carmoflu, galotetabine, imitofuride, capecitabine, etc.), aminopterin, nerabine, leucovorin, methotrexate, butocin, calcium leucovorin, leucovorin, cladribine, imitofuride, fludarabine, gemcitabine, hydroxyurea, pentostatin, pyrithione, idoxuridine, mitoxuridine, thiazofuran, abamustine, bendamustine, and their DDS preparations.

[0362] Examples of "anticancer antibiotics" include actinomycin D, actinomycin C, mitomycin C, chromomycin A3, bleomycin hydrochloride, bleomycin sulfate, pepromycin sulfate, daunorubicin hydrochloride, doxorubicin hydrochloride, aclarubicin hydrochloride, pirarubicin hydrochloride, epirubicin hydrochloride, neocarzinostatin, photomycin, sarkomycin, carzinophilin, mitotane, zorubicin hydrochloride, mitoxantrone hydrochloride, idarubicin hydrochloride, eribulin, and their DDS preparations.

[0363] Examples of "plant-derived anticancer agents" include etoposide, etoposide phosphate, vincristine sulfate, vinblastine sulfate, vindesine sulfate, teniposide, paclitaxel, docetaxel, DJ-927, vinorelbine, irinotecan, topotecan, and their DDS formulations.

[0364] Examples of "molecularly targeted therapies" include imatinib, gefitinib, erlotinib, sorafenib, dasatinib, sunitinib, nilotinib, lapatinib, pazopanib, ruxotinib, crizotinib, vemurafenib, vandetanib, ponatinib, cabozantinib, tofacitinib, regorafenib, bosutinib, axitinib, dabrafenib, trametinib, nintedanib, ederaris, ceritinib, lenvatinib, palbociclib, alectinib, afatinib, osimertinib, ribociclib, abeciclib, and brigatinib. Tinib, neratinib, copanlisib, cobitinib, ibrutinib, acalatinib, encorafenib, bimetinib, baricitinib, fantatinib, lorlatinib, erdatinib, entrectinib, dacomitinib, sirolimus, everolimus, tesimolimus, olaparib, rucaparib, niraparib, venetoclax, azacitidine, decitabine, vorinostat, pabistat, tazestat, romidesin, bortezomib, carfilzomib, larotrectinib, ixazomib, etc.

[0365] Examples of "immunomodulators" include lenalidomide and pomalidomide.

[0366] Examples of “other chemotherapy agents” include sobuzosen, etc.

[0367] Examples of “immunotherapy agents (BRM)” include picibanil, krestin, sizofiran, lentinan, ubenimex, interferon, interleukin, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, erythropoietin, lymphotoxin, BCG vaccine, Corynebacterium breve, levamisole, polysaccharide K, procodazole, anti-CTLA4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, and Toll-like receptor agonists (e.g., TLR7 agonists, TLR8 agonists, TLR9 agonists, etc.).

[0368] Cell growth factors in agents that inhibit the action of cell growth factors and their receptors can be any substance that promotes cell growth. Cell growth factors are typically peptides with a molecular weight of 20,000 or less, and exert their effects at low concentrations by binding to receptors. Specific examples include EGF (epidermal growth factor) or substances with essentially the same activity as EGF (such as TGF-α), insulin or substances with essentially the same activity as insulin (such as insulin, IGF (insulin-like growth factor)-1, IGF-2, etc.), FGF (fibroblast growth factor) or substances with essentially the same activity as FGF (such as acidic FGF, basic FGF, KGK (keratinocyte growth factor), FGF-10, etc.), and other cell growth factors (such as CSF (colony-stimulating factor), EPO (erythropoietin), IL-2 (interleukin-2), NGF (nerve growth factor), PDGF (platelet-derived growth factor), TGF-β (transforming growth factor β), HGF (hepatocyte growth factor), VEGF (vascular endothelial growth factor), heregulin, angiopoietin, etc.).

[0369] "SMARC-deficient cancer" is a cancer with a deficiency in the SMARC gene and / or loss or attenuation of SMARC protein expression. Preferably, it is a cancer with a deficiency in the SMARC gene and / or loss of SMARC protein expression. More preferably, it is a cancer with a deficiency in the SMARCB1 gene, SMARCA2 gene, SMARCA4 gene, or SMARCA2 / A4 gene. Specific examples include malignant rhabdoid tumors, epithelioid sarcomas, atypical teratomyoid / rhabdoid tumors, schwannomas, chordal meningiomas, neuroepithelial tumors, glial neuronal tumors, craniopharyngiomas, glioblastomas, chordomas, myoepithelial tumors, undifferentiated round cell sarcomas, rhabdomyosarcomas, extraosseous myxoid chondrosarcomas, synovial sarcomas, ossifying fibromyxoid tumors, basal squamous cell carcinoma of the nasal cavity, esophageal adenocarcinoma, papillary thyroid carcinoma, follicular thyroid carcinoma, gastrointestinal stromal tumors, and undifferentiated rhabdoid pancreatic tumors. Tumors, including rhabdoid tumors of the digestive system, renal medullary carcinoma, uterine cancer, myoepithelioma-like tumors of the female vulva, colon cancer, mesothelioma, lung adenocarcinoma, large cell lung cancer, pulmonary neuroendocrine tumors, esophageal cancer, gastroesophageal junction cancer, gastric cancer, bladder cancer, lung squamous cell carcinoma, pancreatic cancer, medulloblastoma, clear cell renal carcinoma, liver cancer, small cell ovarian cancer, mucinous ovarian tumors, uterine cancer, uterine sarcoma, nasal cavity and sinus cancer, pleural sarcoma, pleomorphic carcinoma, chest sarcoma, small cell ovarian cancer, primary gallbladder tumors, and uterine sarcoma. Malignant rhabdoid tumors and lung adenocarcinomas are preferred.

[0370] "SMARCB1-deficient cancer" is a cancer with a defect in the SMARCB1 gene and / or a lack or reduction in the expression of the SMARCB1 protein. Preferably, it is a cancer with a defect in the SMARCB1 gene and / or a lack of expression of the SMARCB1 protein. More preferably, it is a cancer with a defect in the SMARCB1 gene. Specific examples include malignant rhabdoid tumors, epithelioid sarcomas, atypical teratoid / rhabdoid tumors, schwannomas, chordal meningiomas, neuroepithelial tumors, glial neuron tumors, craniopharyngiomas, glioblastomas, chordomas, myoepithelial tumors, undifferentiated round cell sarcomas, rhabdomyosarcomas, extraosseous myxoid chondrosarcomas, synovial sarcomas, ossifying fibromyxoid tumors, basal squamous cell carcinomas of the nasal cavity, esophageal adenocarcinomas, papillary thyroid carcinomas, follicular thyroid carcinomas, gastrointestinal stromal tumors, undifferentiated rhabdoid tumors of the pancreas, rhabdoid tumors of the digestive system, renal medullary carcinomas, uterine cancer, myoepithelioid tumors of the female vulva, colon cancer, and mesotheliomas. Malignant rhabdoid tumors are preferred.

[0371] "SMARCA2-deficient cancer" is a cancer with a defect in the SMARCA2 gene and / or absent or weakened expression of the SMARCA2 protein. Preferably, it is a cancer with a defect in the SMARCA2 gene and / or absent expression of the SMARCA2 protein. More preferably, it is a cancer with a defect in the SMARCA2 gene. Specific examples include lung adenocarcinoma, large cell lung cancer, pulmonary neuroendocrine tumors, esophageal cancer, gastroesophageal junction cancer, and malignant rhabdomyosarcoma. Lung adenocarcinoma is preferred.

[0372] "SMARCA4-deficient cancer" is a cancer with a defect in the SMARCA4 gene and / or loss or attenuation of SMARCA4 protein expression. Preferably, it is a cancer with a defect in the SMARCA4 gene and / or loss of SMARCA4 protein expression. More preferably, it is a cancer with a defect in the SMARCA4 gene. Specific examples include lung adenocarcinoma, esophageal cancer, gastroesophageal junction cancer, gastric cancer, bladder cancer, squamous cell carcinoma of the lung, pancreatic cancer, medulloblastoma, clear cell carcinoma of the kidney, liver cancer, small cell carcinoma of the ovary, mucinous ovarian tumor, uterine cancer, mesothelioma, uterine sarcoma, nasal cavity and sinus cancer, rhabdomyosarcoma, and thoracic sarcoma. Lung adenocarcinoma is preferred.

[0373] "SMARCA2 / A4 deficient cancer" is a cancer with defects in the SMARCA2 and SMARCA4 genes and / or loss or attenuation of SMARCA2 and SMARCA4 protein expression. Preferably, it is a cancer with defects in the SMARCA2 and SMARCA4 genes and / or loss of SMARCA2 and SMARCA4 protein expression. More preferably, it is a cancer with defects in both the SMARCA2 and SMARCA4 genes. Specific examples include lung adenocarcinoma, pleomorphic carcinoma, large cell lung cancer, esophageal cancer, gastroesophageal junction cancer, thoracic sarcoma, small cell ovarian cancer, primary gallbladder tumor, uterine sarcoma, malignant rhabdoid tumor, ovarian granulosa cell tumor, adrenocortical carcinoma, and small cell lung cancer. Lung adenocarcinoma is preferred.

[0374] "ARID-deficient cancer" is a cancer with ARID gene defects and / or absent or weakened ARID protein expression. Preferably, it is a cancer with ARID gene defects and / or absent ARID protein expression. More preferably, it is a cancer with defects in the ARID1A gene, ARID1B gene, or ARID1A / 1B gene. Specific examples include ovarian cancer, gastric cancer, bile duct cancer, pancreatic cancer, uterine cancer, neuroblastoma, colon cancer, bladder cancer, liver cancer, melanoma, breast cancer, medulloblastoma, and neuroblastoma. Ovarian cancer is preferred.

[0375] "ARID1A-deficient cancer" is a cancer with an ARID1A gene defect and / or absent or weakened ARID1A protein expression. Preferably, it is a cancer with an ARID1A gene defect and / or absent ARID1A protein expression. More preferably, it is a cancer with an ARID1A gene defect. Specific examples include ovarian cancer, gastric cancer, bile duct cancer, pancreatic cancer, uterine cancer, neuroblastoma, colon cancer, and bladder cancer. Ovarian cancer is preferred.

[0376] "ARID1B-deficient cancer" is a cancer characterized by a deficiency in the ARID1B gene and / or loss or attenuation of ARID1B protein expression. Preferably, it is a cancer characterized by a deficiency in the ARID1B gene and / or loss of ARID1B protein expression. More preferably, it is a cancer characterized by a deficiency in the ARID1B gene. Specific examples include ovarian cancer, colon cancer, pancreatic cancer, liver cancer, melanoma, breast cancer, medulloblastoma, uterine cancer, bladder cancer, and gastric cancer. Ovarian cancer is preferred.

[0377] "ARID1A / 1B deficient cancer" is a cancer with defects in the ARID1A and ARID1B genes and / or loss or attenuation of ARID1A and ARID1B protein expression. Preferably, it is a cancer with defects in the ARID1A and ARID1B genes and / or loss of ARID1A and ARID1B protein expression. More preferably, it is a cancer with defects in both the ARID1A and ARID1B genes. Specific examples include ovarian cancer, colon cancer, uterine cancer, neuroblastoma, bladder cancer, and gastric cancer. Ovarian cancer is preferred.

[0378] "SS18-SSX fusion cancer" refers to cancers in which the SS18 gene and the SSX gene are fused. Specific examples include synovial sarcoma and Ewing's sarcoma. Synovial sarcoma is preferred.

[0379] "Heart disease" is a condition caused by various disorders of the heart that lead to a failure of blood circulation. Specific examples include cardiomyopathy, heart failure, and myocardial infarction.

[0380] Metabolic diseases are illnesses caused by metabolic dysfunction. Specific examples include dyslipidemia and diabetes.

[0381] There are no limitations on the dosing period of the disclosed compounds and other drugs. They can be administered simultaneously or alone to the target. The disclosed compounds and other drugs can also be formulated as combination drugs. The amount of the other drug to be administered can be appropriately selected based on the clinically used dosage. The blending ratio of the disclosed compounds and other drugs can be appropriately selected according to the subject, route of administration, target disease, symptoms, combination, etc. For example, if the subject is a human, 0.01 to 100 parts by weight of the other drug can be used relative to 1 part by weight of the disclosed compound. They can also be used in combination with agents such as antiemetics, sleep inducing agents, or anticonvulsants (other drugs) to suppress their side effects.

[0382] As used in this article, "or" is used when there are "at least one or more" items listed in the sentence. When explicitly described in this article as "within a range of two values," that range also includes the two values ​​themselves.

[0383] References cited in this article, such as scientific literature, patents, and patent applications, are incorporated herein by reference to the same extent that each reference is specifically described in its full text.

[0384] For ease of understanding, preferred embodiments have been shown alongside the description of this disclosure. Although the disclosure is described below based on embodiments, the foregoing description and the following embodiments are provided for illustrative purposes only and are not intended to limit the disclosure. Therefore, the scope of this disclosure is not limited to the embodiments and examples specifically described herein, but is limited only by the scope of the claims.

[0385] [Example] The present disclosure will be described in more detail below with reference to examples, embodiments and test examples, but the disclosure is not limited thereto.

[0386] The following abbreviations may be used in this instruction manual.

[0387] Me: Methyl Et: Ethyl Ph: phenyl Bn: Benzyl Boc: tert-Butoxycarbonyl DMPU: N,N'-Dimethylacrylurea n-: positive- tert-: Uncle- p-: to- Ac: Acetyl group dppf: 1,1'-bis(diphenylphosphino)ferrocene X-PHOS: 2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl.

[0388] NMR (nuclear magnetic resonance) data used to identify the compounds were obtained using a JNM-ECS 400 NMR spectrometer (400 MHz) (JEOL Ltd.).

[0389] In NMR, the symbols s represent a singlet, d a doublet, dd a doublet, t a triplet, td a doublet of triplets, q a quartet, m a multiplet, br a broad peak, brs a broad singlet, brm a broad multiplet, and J a coupling constant.

[0390] The LC / MS (liquid chromatography-mass spectrometry) analytical conditions used for compound identification are as follows. In the observed mass spectrometry values ​​[MS(m / z)], the values ​​corresponding to the monoisotopic mass (the precise mass composed only of the major isotope) are derived from [M+H]. + [MH] - Or [M+2H] 2+ The values ​​are represented as Rt (minutes), and the retention time is represented as Rt (minutes).

[0391] LC / MS measurement method: Detector: ACQUITY (registered trademark) SQ detector (Waters) HPLC: ACQUITY UPLC (registered trademark) system Chromatographic column: Waters ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm, 2.1 mm × 30 mm) Solvents: Solution A: 0.06% formic acid / H₂O, Solution B: 0.06% formic acid / MeCN Gradient condition: 0.0-1.3 minutes, linear gradient from B 2% to 96%. Flow rate: 0.8 mL / min UV: 220 nm and 254 nm Column temperature: 40℃.

[0392] Reference Example 1 N-(4-Fluorobenzyl)-2-hydroxy-N-(3-(trifluoromethyl)oxetane-3-yl)acetamide [Chemical Formula 26] a) Preparation of N-(4-fluorobenzyl)-3-(trifluoromethyl)oxetane-3-amine (compound Y1) 10.0 g of 3-(trifluoromethyl)oxetane-3-amine hydrochloride was dissolved in chloroform (188 mL), and 7.25 mL of 4-fluorobenzaldehyde and 22.4 g of sodium triacetoxyborohydride were added at 0 °C. The mixture was stirred at room temperature for 16 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (10.6 g).

[0393] LC-MS([M+H] + / Rt(min)):250.1 / 0.936.

[0394] b) Preparation of 2-(benzyloxy)-N-(4-fluorobenzyl)-N-(3-(trifluoromethyl)oxetane-3-yl)acetamide (compound Y2) Compound Y1 (7.6 g) was dissolved in DMPU (102 mL), sodium hydride (2.0 g) was added at 0 °C, and the mixture was stirred at room temperature for 30 min. Benzyloxyacetyl chloride (12.0 mL) was added at 0 °C, and the mixture was stirred at room temperature for 5 h. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (10.8 g).

[0395] LC-MS([M+H] + / Rt(min)):398.2 / 1.034.

[0396] c) Preparation of N-(4-fluorobenzyl)-2-hydroxy-N-(3-(trifluoromethyl)oxetane-3-yl)acetamide Compound Y2 (15.1 g) was dissolved in methanol (127 mL), and palladium hydroxide-activated carbon (2.1 g) was added. The mixture was stirred at room temperature for 4 hours under a hydrogen atmosphere. The mixture was filtered through diatomaceous earth, the residue was washed with methanol, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (11.0 g).

[0397] LC-MS([M+H] + / Rt(min)):308.1 / 0.745.

[0398] Refer to Examples 2 to 5 According to the method described in Reference Example 1, the compounds of Reference Examples 2 to 6 are obtained using the corresponding raw material compounds.

[0399] See Example 8 (3'R,4S)-5'-bromo-3'-fluoro-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-2,5-dione [Chemical Formula 27] a) Preparation of (3'S,4S)-5'-bromo-3'-hydroxy-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-2,5-dione (compound Y3) (4S)-5'-bromospiro(imidazolidine-4,1'-indene)-2,3',5(2'H)-trione (20.0 g) was dissolved in methanol (339 mL), and sodium borohydride (2.8 g) was added at -78 °C. The mixture was stirred at 0 °C for 1 hour. A saturated aqueous solution of ammonium chloride was added to the reaction mixture at 0 °C. The reaction mixture was extracted twice with an ethyl acetate / methanol mixture. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure to give the title compound (19.0 g).

[0400] LC-MS ([M+H]+ / Rt (min)): 297.0 / 0.529.

[0401] b) Preparation of (3'R,4S)-5'-bromo-3'-fluoro-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-2,5-dione Compound Y3 (18.6 g) was dissolved in dichloromethane (313 mL), and (diethylamino)sulfur trifluoride (28.9 mL) was added at -78 °C. The mixture was stirred at 0 °C for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture at 0 °C. The reaction mixture was extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (15.6 g).

[0402] LC-MS ([M+H]+ / Rt (min)): 299.0 / 0.681.

[0403] See Example 9 (S)-2-(5'-bromo-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(4-fluorobenzyl)-N-(3-(trifluoromethyl)oxetane-3-yl)acetamide [Chemical Formula 28] The compound of Reference Example 1 (264 mg) was dissolved in tetrahydrofuran (3 mL), and (S)-5'-bromo-2',3'-dihydrospiro(imidazolidine-4,1'-indene)-2,5-dione (230 mg), diisopropyl azodicarbonate (0.56 mL), and triphenylphosphine (279 mg) were added at 0 °C. The mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (460 mg).

[0404] LC-MS ([M+H]+ / Rt (min)): 572.3 / 1.038.

[0405] Refer to Examples 10 to 16 According to the method described in Reference Example 9, the compounds of Reference Examples 10 to 16 are obtained using the corresponding raw material compounds.

[0406] See Example 17 (S)-2-(5'-bromo-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl)acetamide [Chemical Formula 29] a) The compound of Reference Example 3 (1.83 g) was dissolved in tetrahydrofuran (29 mL), and (S)-5'-bromo-2',3'-dihydrospiro(imidazolidine-4,1'-indene)-2,5-dione (1.21 g), bis(2-methoxyethyl) azodicarbonate (1.3 g), and triphenylphosphine (1.5 g) were added at 0 °C, and the mixture was stirred at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound.

[0407] LC-MS ([M+H]+ / Rt (min)): 615.2 / 1.178.

[0408] b) Preparation of (S)-2-(5'-bromo-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl)-N-(1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl)acetamide The obtained compound Y4 was dissolved in chloroform (17 mL), and trifluoroacetic acid (13.2 mL) was added at room temperature. The mixture was stirred for 5 hours. The reaction mixture was concentrated under reduced pressure and azeotropically reacted with toluene. The obtained crude substance was dissolved in chloroform (21 mL), and 37% formalin aqueous solution (1.4 mL) and sodium triacetoxyborohydride (2.7 g) were added at 0 °C. The mixture was stirred at room temperature for 15 hours. Saturated sodium bicarbonate aqueous solution was added to the reaction mixture at 0 °C. The reaction mixture was extracted twice with chloroform. The obtained organic layer was washed with saturated brine and dried over magnesium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by aminosilica gel column chromatography (hexane / ethyl acetate) to give the title compound (1.16 g).

[0409] LC-MS ([M+H]+ / Rt (min)): 583.3 / 0.778.

[0410] See Examples 18 to 22 According to the method described in Reference Example 17, the compounds of Reference Examples 18 to 22 are obtained using the corresponding raw material compounds.

[0411] Example 1 N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide [Chemical Formula 30] The compound of Reference Example 9 (100 mg) was dissolved in 1,4-dioxane (0.7 mL) and water (0.2 mL), and potassium carbonate (52 mg), 1-(1-(oxecyclobutane-3-yl)azacyclobutane-3-yl)-1H-pyrazole-4-borate pinacol ester (68 mg) and [1,1'-bis(diphenylphosphine)ferrocene]palladium(II) dichloride (14 mg) were added at room temperature, and the mixture was stirred at 90 °C for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The obtained organic layer was washed with saturated brine and dried over sodium sulfate. It was removed by filtration, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / methanol) to give the title compound (29 mg).

[0412] LC-MS ([M+H]+ / Rt (min)): 669.5 / 1.005.

[0413] Examples 2 to 35 According to the method described in Example 1, the compounds of Examples 2 to 35 were obtained using corresponding reference example compounds and commercially available compounds as raw materials.

[0414] Comparative Example 1 [Chemical Formula 31] The compound of Comparative Example 1 was obtained by the method described in WO 2016 / 044770.

[0415] LC-MS ([M+H]+ / Rt (min)): 619.4 / 0.938.

[0416] Comparative Example 2 [Chemical Formula 32] The compound of Comparative Example 2 was obtained by the method described in WO 2020 / 108500.

[0417] LC-MS ([M+H]+ / Rt (min)): 531.3 / 0.965.

[0418] Test case The test results of representative compounds disclosed herein are shown below, and the pharmacological, chemical and pharmacokinetic properties of the compounds are explained below, but this disclosure is not limited to these test examples.

[0419] Experimental Example 1: HAT Activity Inhibition Experiment The HAT activity inhibitory activity of the HAT inhibitors was evaluated using the SensoLyte HAT (p300) Assay Kit (ANASPEC, AS-72172). Specifically, 7.5 μL of the compounds from Examples 1 to 35 diluted with assay buffer was added to 7.5 μL of recombinant p300 solution diluted 10-fold with assay buffer, and the mixture was incubated at room temperature for 10 min. Then, 7.5 μL of acetyl-CoA solution diluted 10-fold with assay buffer and 15 μL of histone H3 peptide diluted 10-fold with assay buffer were added, and the mixture was incubated at 37°C for 30 min. The reaction was terminated by adding 37.5 μL of stop solution. Finally, 75 μL of p300 chromogenic reagent solution diluted 50-fold with assay buffer was added, and the mixture was incubated at room temperature under light-shielded conditions for 30 min. Fluorescence at 513 nm under 389 nm excitation light was measured using a multi-plate reader. Based on the measured fluorescence intensity, the IC50 was calculated. 50 The value corresponds to the concentration of the compound that shows 50% inhibition of the enzyme reaction. The results are shown in Table 5.

[0420] As shown in Table 5, a series of compounds of the present invention are confirmed to inhibit the function of the HAT domain of P300 / CBP. In particular, Examples 3 to 5, 7, 9 to 13, 15, 17, 18 to 20, 23 to 27 and 29 to 35 show strong inhibition of HAT activity.

[0421] Experiment 2: Cell proliferation inhibition experiment using G-401 cells G-401 cells (derived from malignant rhabdomyosarcoma) were obtained from the American Type Culture Collection (ATCC). G-401 cells were cultured in McCoy's 5A medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C and 5% CO2.

[0422] 500 cells per well were seeded into 384-well plates. One day after seeding, DMSO from Examples 1 to 35 was added to achieve a final concentration of 0.1%, and the cells were cultured for 3 days. After culture, cell viability was measured using the CellTiter-Glo Luminescent Cell Viability Assay (Promega, G7570). IC50 was calculated from the viability curve. 50 The value corresponds to the concentration of the evaluation compound that showed 50% inhibition of cell proliferation. The results are shown in Table 6.

[0423] As shown in Table 6, a series of compounds of the present invention exhibit strong inhibitory effects on G-401 cells (which are derived from malignant rhabdoid tumors). In particular, Examples 2 to 5, 7, 9 to 13, 15, 17, 19, 20, 22 to 27 and 29 to 35 showed strong inhibitory effects on cell proliferation.

[0424] Experiment 3: Cell proliferation inhibition experiment using Kuramochi cells Kuramochi cells (derived from ovarian cancer) were obtained from the JCRB (Japanese Collection of Research Bioresources) cell bank. Kuramochi cells were cultured in RPMI-1640 medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C and 5% CO2.

[0425] 500 cells per well were seeded into 384-well plates. One day after seeding, DMSO solutions from Examples 3, 7, 9, 10, 11, 20, 23 to 25, and 30 to 34 were added to bring the final concentration of DMSO to 0.1%, and the cells were cultured for 6 days. After culture, cell viability was measured using the CellTiter-Glo luminescent cell viability assay kit (Promega, G7570). IC50 was calculated from the viability curve. 50 The value corresponds to the concentration of the evaluation compound that showed 50% inhibition of cell proliferation. The results are shown in Table 7.

[0426] Experiment 4: Cell proliferation inhibition experiment using RMGI cells RMGI cells (derived from ovarian cancer) were obtained from the JCRB cell bank. RMGI cells were cultured in Ham's F12 medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C and 5% CO2.

[0427] 200 cells per well were seeded into 384-well plates. One day after seeding, DMSO solutions 3, 7, 9, 10, 11, 20, and 23 to 25 were added to bring the final concentration to 0.1%, and the cells were cultured for 6 days. After culture, cell viability was measured using the CellTiter-Glo luminescent cell viability assay kit (Promega, G7570). IC50 was calculated from the viability curve. 50 The value corresponds to the concentration of the evaluation compound that showed 50% inhibition of cell proliferation. The results are shown in Table 8.

[0428] Experimental Example 5: Solubility Test Solubility measurements were performed on Examples 7, 10, 20, 23, 24 and 30 to 34, and Comparative Examples 1 and 2. The test compounds were added to 10 mmol / L glycine buffer (pH 2.0) and 10 mmol / L citrate buffer (pH 3.0), and the mixtures were stored at a constant temperature of 5°C. After standing overnight, the mixtures were filtered through a membrane filter, and the concentration of the filtrate was measured by HPLC.

[0429] The HPLC measurement conditions are as follows.

[0430] HPLC conditions Column: Acquity UPLC BEH C18, 1.7 μm, 50×2.1 mm Column temperature: 40℃ Mobile phase: A: Water containing 0.1% trifluoroacetic acid B: Acetonitrile A / B(min):95 / 5(0)→0 / 100(3.5)→0 / 100(4)→95 / 5(4.01)→95 / 5(5) Flow rate: 0.8 mL / min Detection: UV-Vis detector, measurement wavelength 254 nm Injection volume: 5 μL or Column: Acquity UPLC BEH C18, 1.7 μm, 50×2.1 mm Column temperature: 40℃ Mobile phase: A: Water containing 0.1% trifluoroacetic acid B: Acetonitrile A / B(min): 80 / 20(0)→40 / 60(3.0)→0 / 100(3.5)→0 / 100(4)→80 / 20(4.01)→80 / 20(5) Flow rate: 0.8 mL / min Detection: UV-Vis detector, measurement wavelength 254 nm Injection volume: 2 μL or Column: Acquity UPLC BEH C18, 1.7 μm, 50×2.1 mm Column temperature: 40℃ Mobile phase: A: Water containing 0.1% trifluoroacetic acid B: Acetonitrile A / B(min): 80 / 20(0)→40 / 60(3.0)→0 / 100(3.5)→0 / 100(4)→100 / 0(4.01)→100 / 0(5) Flow rate: 0.8 mL / min Detection: UV-Vis detector, measurement wavelength 254 nm Injection volume: 3 μL The results are shown in Table 9.

[0431] Examples 7, 10, 20, 23, 24, and 30 to 34 exhibited high solubility. On the other hand, Comparative Examples 1 and 2 showed extremely low solubility of 0.002 mg / mL, 0.004 mg / mL, and 0.005 mg / mL at pH 2.0 and pH 3.0, respectively. The experimental results confirm that Examples 7, 10, 20, 23, 24, and 30 to 34 are compounds that exhibit outstanding solubility effects.

[0432] Test Example 6: Membrane permeability test The membrane permeability of the test compound was tested using a parallel artificial membrane permeability assay (PAMPA) as follows: 200 μL of system solution (pION Inc.) containing the test compound and 4 μL of GIT Lipid-0 (pION Inc.) were added to the donor plate. 200 μL of acceptor sink buffer (pION Inc.) was added to the acceptor plate. The two plates were overlapped and incubated at 37°C for 4 hours, after which the UV absorbance of the acceptor and donor side solutions was measured using a UV plate reader (190-500 nm). Compounds with poor UV absorbance were measured using LC-MS. The permeability coefficient Pe (10⁻¹⁰) of the drug was calculated using the following formula. -6 cm / sec).

[0433] The results are shown in Table 10.

[0434] Experimental Example 7: Pharmacokinetic Study in Mice The test compound was administered intravenously in 50% PEG solution (0.01 mol / L HCl) (dose: 1 mg / kg) or orally in 0.5% methylcellulose aqueous solution (dose: 10 mg / kg) to 7-week-old female BALB / c (BALB / cAnNCrlCrlj) mice, and blood was collected at the following time points: Intravenous administration: 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours after administration. Oral administration: 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, and 24 hours after administration. Blood samples were centrifuged at 3000 rpm for 10 minutes using a refrigerated centrifuge set to 4°C, and the resulting plasma was measured by LC-MS. A calibration curve was prepared by dividing the peak area of ​​the test substance in the MS by the peak area of ​​the internal standard (peak ratio) and using the plasma calibration curve sample concentrations. The concentrations in the samples were calculated from the peak ratios and the calibration curves for each sample.

[0435] The results of Examples 1, 3 to 5, 7, 9 to 12, 20 and 23 to 25 are shown in Table 11.

[0436] The experimental results confirm that the compounds of this invention have excellent pharmacokinetic properties and are useful in vivo.

[0437] Experiment Example 8: Evaluation of drug efficacy through oral administration in G-401 xenograft model mice G-401 cells (ATCC) were used at a rate of 5 × 10⁻⁶. 5 One cell / mouse intradermal transplantation into 4-7 week old BALB / cAnNCrj-nu / nu mice (CAnN.Cg-Foxn1) <nu>(CrlCrlj, Jackson Laboratory Japan). After confirming G-401 cell engraftment 10–40 days post-transplantation, the test compound, suspended in a solvent such as 0.5% methylcellulose solution, was orally administered twice daily at a dose of 1–100 mg / kg. Tumor volume was measured over time from the start of administration, and the reduction in tumor volume caused by the test compound was evaluated. Tumor volume was calculated using the minor axis and major axis of the tumor measured with electronic calipers (Mitutoyo) using the following formula.

[0438] Tumor volume [mm] 3 = 0.5 × minor diameter [mm] × (major diameter [mm]) 2 .

[0439] The control group and the test compound group were compared using solvents such as 0.5% methylcellulose solution, and the antitumor effect was evaluated by calculating the T / C ratio using the following formula.

[0440] T / C (%) = (Tumor volume at the end of administration in the test compound group - Tumor volume at the beginning of administration in the test compound group) / (Tumor volume at the end of administration in the control group - Tumor volume at the beginning of administration in the control group) × 100.

[0441] The results of Examples 7, 10, 20 and 23 are shown in Table 12.

[0442] Based on the experimental results, Examples 7, 10, 20 and 23 showed strong anti-tumor effects in the G-401 xenograft model (a cell line derived from malignant rhabdoid tumor).

[0443] Experiment Example 9: Evaluation of drug efficacy via intravenous administration using a G-401 xenograft mouse model G-401 cells (ATCC) were used at a rate of 5 × 10⁻⁶. 5 One cell / mouse intradermal transplantation into 4-7 week old BALB / cAnNCrj-nu / nu mice (CAnN.Cg-Foxn1) <nu> / CrlCrlj, Jackson Laboratory Japan). After confirming G-401 cell engraftment 10–40 days post-transplantation, the test compound, suspended in a solvent such as 10 mmol / L glycine buffer (pH 2.0), was administered via tail vein at a dose of 0.015–20 mg / kg at least once weekly. Tumor volume was measured over time from the start of administration, and the reduction in tumor volume caused by the test compound was evaluated. Tumor volume was calculated using the short and long diameters of the tumor measured with electronic calipers (Mitutoyo) using the following formula.

[0444] Tumor volume [mm] 3 = 0.5 × minor diameter [mm] × (major diameter [mm]) 2 .

[0445] The control group and the test compound group were compared using a solvent such as 10 mmol / L glycine buffer solution (pH 2.0), and the antitumor effect was evaluated by calculating the T / C ratio using the following formula.

[0446] T / C (%) = (Tumor volume at the end of administration in the test compound group - Tumor volume at the beginning of administration in the test compound group) / (Tumor volume at the end of administration in the control group - Tumor volume at the beginning of administration in the control group) × 100.

[0447] The results of Examples 7, 10, 20, 23 and 24 and Comparative Example 1 are shown in Table 13.

[0448] Based on the experimental results, Examples 7, 10, 20, 23, and 24 showed strong antitumor effects even when administered intravenously in the G-401 xenograft model (which is derived from cells of malignant rhabdoid tumor). On the other hand, Comparative Example 1 did not show any antitumor effect even when administered at the maximum concentration.

[0449] Experimental Example 10: Evaluation of Dopamine Receptor Inhibitory Activity The binding assay was outsourced to Eurofins. Specifically, CHO-S / hDAT cells were homogenized in an incubation buffer consisting of 50 mmol / L Tris-HCl (pH 7.4), 100 mmol / L NaCl, 1 μmol / L leupeptin, and 10 μmol / L PMSF. The membrane pellet obtained by centrifugation was resuspended in the incubation buffer to prepare the membrane preparation. The test compound (1–10 μmol / L DMSO solution), the membrane preparation, and 0.15 nmol / L [3H]kparoxetine were mixed and incubated at 4°C for 180 min. The cell membrane-[125I]RTI-55 complex was bound to a GF / B filter pad by vacuum filtration and washed with 50 mmol / L Tris-HCl (pH 7.4). The effect on the receptor was evaluated by measuring radioactivity using a scintillation counter.

[0450] The results are shown in Table 14.

[0451] Experiment 11: Evaluation of Serotonin Receptor Inhibitory Activity The binding assay was outsourced to Eurofins. Specifically, HEK293 / hSERT cells were homogenized in a buffer consisting of 100 mmol / L NaCl, 1 μmol / L leucopeptide, 10 μmol / L PMSF, and 50 mmol / L Tris-HCl (pH 7.4). The membrane precipitate obtained by centrifugation was resuspended in an incubation buffer consisting of 50 mmol / L Tris-HCl (pH 7.4), 120 mmol / L NaCl, and 5 mmol / L KCl to prepare the membrane preparation. The test compound (1–10 μmol / L DMSO solution), the membrane preparation, and 0.4 nmol / L [3H]paroxetine were mixed and incubated at 25°C for 60 min. The cell membrane-[3H]paroxetine complex was bound to a GF / B filter pad by vacuum filtration and washed with 50 mmol / L Tris-HCl (pH 7.4). The effect on the receptor was evaluated by measuring radioactivity using a scintillation counter.

[0452] The results are shown in Table 15.

[0453] The results of Test Examples 10 and 11 confirm that the disclosed compounds do not act on off-targets that could cause safety concerns. On the other hand, Comparative Example 2 reveals a strong inhibitory effect on dopamine and serotonin receptors.

[0454] Based on the results of Test Examples 1 to 11, the disclosed compounds exhibited strong HAT inhibitory activity (Test Example 1) and strong inhibitory effects on cancer cell proliferation (Test Examples 2 to 4). Furthermore, the disclosed compounds exhibited excellent solubility (Test Example 5), high membrane permeability (Test Example 6), and favorable pharmacokinetics (Test Example 7), as well as outstanding antitumor effects (Test Example 8). In addition, the disclosed compounds showed outstanding antitumor effects in xenograft model mice, even when administered intravenously (Test Example 9), and due to the absence of strong inhibitory activity against off-target dopamine and serotonin receptors, they also demonstrated remarkably heterogeneous safety (Test Examples 10 and 11).

[0455] The inventors have discovered a new problem with the low solubility of Comparative Examples 1 and 2, which makes intravenous administration difficult. Generally, when structural transformation is performed to increase solubility, lipophilicity is reduced and membrane permeability is impaired. However, the compounds of the present invention, especially those represented by formulas (2) to (7), have the effect of combining excellent solubility (Example 5) and high membrane permeability (Example 6), and are therefore excellent CBP / P300 inhibitors that can be administered orally and intravenously.

[0456] Among the compounds of the present invention, Examples 7, 10, 20, 23, 24, 25, and 30 to 34, comprising formulas (2), (3), (5), or (6), exhibited strong HAT inhibitory activity (Example 1) and strong cancer cell proliferation inhibitory effects (Examples 2 to 4). Furthermore, while lipophilicity is typically reduced and membrane permeability impaired when structural transformations are performed to increase solubility, Examples 7, 10, 20, 23, 24, and 30 to 34 combine better solubility than Comparative Examples 1 and 2 (Example 5) and membrane permeability comparable to Comparative Examples 1 and 2 (Example 6), achieving a balance of multiple properties. In addition, Examples 7, 10, 20, 23, and 24 exhibited excellent pharmacokinetics (Example 7). Examples 7, 10, 20, and 23 showed outstanding antitumor effects upon oral administration (Example 8) and also exhibited extremely significant antitumor effects in tumors unattainable by Comparative Example 1 upon intravenous administration (Example 9). Therefore, they are CBP / P300 inhibitors with profiles suitable for oral and intravenous administration. Furthermore, although Comparative Example 2 showed strong inhibitory activity against off-target dopamine and serotonin receptors, Examples 7, 10, 20, 23, 24, and 25 did not show strong inhibitory activity, demonstrating a remarkably high level of safety that balances multiple characteristics (Examples 10 and 11).

[0457] (Note) As described above, although this disclosure has been illustrated using its preferred embodiments, it is understood that the scope of this disclosure should be interpreted solely by the claims. It is understood that patents, patent applications, and other documents referenced herein are incorporated by reference to the same extent as they are specifically set forth herein.

[0458] [Industrial Applicability] The disclosed compounds and their pharmaceutically acceptable salts can be used as therapeutic or preventative agents for conditions involving CBP / P300 by potently inhibiting CBP / P300.< / nu> < / nu>

Claims

1. Compounds represented by the following formula: [Chemical Formula 1] in A represents CHF or CH2. B represents the following formula (B-1): [Chemical Formula 2] in Indicates the bonding position with the nitrogen atom on the hydantoin ring. Ring Q represents an optionally substituted 6- to 10-membered aromatic ring or an optionally substituted 5- to 10-membered aromatic heterocycle. Z represents -O-, -N(R) 7a )-, optionally substituted 6- to 10-membered divalent aromatic ring groups, optionally substituted 5- to 10-membered divalent aromatic heterocyclic groups, or optionally substituted 4- to 10-membered divalent non-aryl heterocyclic groups, R 1 C represents optional substitution 1-6 Alkyl or optionally substituted C 3-10 Alicyclic groups, R 2a and R 2b Each independently represents an optional substitution of C. 1-6 Alkyl, wherein R 2a and R 2b Together with the carbon atoms they are attached to, they can form optionally substituted C atoms. 3-6 Cycloalkyl or optionally substituted 4- to 6-membered divalent nonaryl heterocyclic groups, R 3 C represents optional substitution 6-10 aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted C 3-10 Alicyclic groups or optionally substituted 4- to 10-membered non-aryl heterocyclic groups, R 4 C represents a single bond or optional substitution. 1-6 Alkylene, optionally substituted C 3-10 Cycloalkyl or optionally substituted 4- to 10-membered divalent nonaryl heterocyclic groups, R 5 C represents hydrogen atom, halogen atom, hydroxyl group, cyano group, or optional substitution. 1-6 Alkyl, optionally substituted C 1-6 alkenyl, optionally substituted C 1-6 alkynyl group, optionally substituted C 1-3 Alkoxy, -NR 7b R 7c -SO2R 7d -CONR 7e R 7f Optional substitution of C 3-10 Alicyclic groups, optionally substituted 4- to 10-membered non-aryl heterocyclic groups, optionally substituted C 6-10 Aryl or optionally substituted 5 to 10-membered heteroaryl, and R 7a R 7b R 7c R 7d R 7e and R 7f Each of the C atoms independently represents a hydrogen atom or an optional substituted C atom. 1-6 alkyl, Or its pharmaceutically acceptable salt.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 R 2a R 2b R 3 R 4 R 5 R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9a R 9b The optionally substituted 6- to 10-membered aromatic rings in rings Q and Z, the optionally substituted 5- to 10-membered aromatic heterocycles, the optionally substituted 6- to 10-membered divalent aromatic ring groups, the optionally substituted 5- to 10-membered divalent aromatic heterocycle groups, and the optionally substituted C 6-10 aryl, the optionally substituted 5- to 10-membered heteroaryl, the optionally substituted 4- to 10-membered non-aryl heterocyclic group, the optionally substituted C 1-6 Alkyl groups, the optionally substituted C 1-6 alkenyl, the optionally substituted C 1-6 alkynyl group, the optional substituted C 3-10 Alicyclic groups, the optionally substituted C 3-6 Cycloalkylene, the optionally substituted 4- to 6-membered divalent nonaryl heterocyclic group, the optionally substituted C 1-6 Alkylene, the optionally substituted C 3-10 Cycloalkylene, the optionally substituted 4- to 10-membered divalent nonaryl heterocyclic group, or the optionally substituted C-membered group 1-3 Each alkoxy group may be independently substituted by one to five identical or different substituents selected from the following: (1) Halogen atom, (2) Hydroxyl group, (3) C 6-10 Aryl, (4) 5- to 12-membered heteroaryl groups, (5) C 1-6 alkyl, (6) C 2-6 alkenyl, (7) C 2-6 alkynyl group, (8) C 1-6 Alkoxy (9) C 1-6 Alkylthio, (10) C 3-10 Alicyclic groups, (11) 3 to 10-membered non-aryl heterocyclic groups, (12) Carboxyl group, (13) -COR 10 , (14) -CO2R 10 , (15) -CONR 11 R 12 , (16) -NR 11 R 12 , (17) -NR 13 COR 10 , (18) -NR 13 CO2R 10 , (19) -NR 13 SO2R 10 , (20) -NR 13 CONR 11 R 12 , (21) -NR 13 SO2NR 11 R 12 , (22) -SO2R 10 , (23) -SO2NR 11 R 12 , (24) -OCOR 10 , (25) -OCO2R 10 , (26) -OCONR 11 R 12 , (27) sulfonyl, (28) Phosphate group, (29) Cyano, and (30) Nitro, Among them, (3) C 6-10 Aryl, (4) 5 to 12-membered heteroaryl, (5) C 1-6 Alkyl, (6) C 2-6 alkenyl, (7) C 2-6 alkynyl group, (8) C 1-6 Alkoxy, (9) C 1-6 Alkylthio, (10) C 3-10 The alicyclic group and (11) the 3 to 10-membered nonaryl heterocyclic group may be optionally substituted by 1 to 5 identical or different substituents selected from the following: (a) Halogen atom, (b) Hydroxyl group, (c) C 6-10 Aryl, (d) 5 to 12-benzyl aryl, (e) C 1-6 alkyl, (f) C 2-6 alkenyl, (g) C 2-6 alkynyl group, (h) C 1-6 Alkoxy (i) C 3-10 Alicyclic groups, (j) 3- to 10-membered non-aryl heterocyclic groups, (k) carboxyl group, (l) -COR 10 , (m) -CO2R 10 , (n) -CONR 11 R 12 , (o) -NR 11 R 12 , (p)-NR 13 COR 10 , (q) -NR 13 SO2R 10 , (r) -SO2R 10 , (s)-SO2NR 11 R 12 , (t) sulfonyl, (u) Phosphate group, (v) cyano, and (w) Nitro, R 10 If multiple cases exist, each is independently designated as C. 1-6 alkyl, R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 Alkyl groups, and if multiple R groups are present 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which it is attached, it can form a 3 to 8-membered nitrogen-containing non-aryl heterocyclic group, and R 13 It is a hydrogen atom or a carbon atom. 1-6 alkyl.

3. The compound of any one of claims 1 to 2, or a pharmaceutically acceptable salt thereof, wherein R 1 R 2a R 2b R 3 R 4 R 5 R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9a R 9b The optionally substituted 6- to 10-membered aromatic rings in rings Q and Z, the optionally substituted 5- to 10-membered aromatic heterocycles, the optionally substituted 6- to 10-membered divalent aromatic ring groups, the optionally substituted 5- to 10-membered divalent aromatic heterocycle groups, and the optionally substituted C 6-10 aryl, the optionally substituted 5- to 10-membered heteroaryl, the optionally substituted 4- to 10-membered non-aryl heterocyclic group, the optionally substituted C 1-6 Alkyl groups, the optionally substituted C 1-6 alkenyl, optionally substituted C 1-6 alkynyl group, the optional substituted C 3-10 Alicyclic groups, the optionally substituted C 3-6 Cycloalkylene, the optionally substituted 4- to 6-membered divalent nonaryl heterocyclic group, the optionally substituted C 1-6 Alkylene, the optionally substituted C 3-10 Cycloalkylene, the optionally substituted 4- to 10-membered divalent nonaryl heterocyclic group, or the optionally substituted C-membered group 1-3 Each alkoxy group may be independently substituted by one to five identical or different substituents selected from the following: (1) Halogen atom, (2) Hydroxyl group, (3) C 6-10 Aryl, (4) 5- to 12-membered heteroaryl groups, (5) C atoms substituted with 1 to 3 halogen atoms 1-6 alkyl, (6) C 2-6 alkenyl, (7) C 2-6 alkynyl group, (8) C 1-6 Alkoxy (9) C 3-10 Alicyclic groups, (10) 3 to 10-membered non-aryl heterocyclic groups, (11) Carboxyl group, (12) -COR 10 , (13) -CO2R 10 , (14) -CONR 11 R 12 , (15) -NR 11 R 12 , (16) -SO2R 10 , (17) -SO2NR 11 R 12 , (18) Sulfonate, (19) Phosphate group, (20) Cyano, and (21) Nitro, R 10 If multiple cases exist, each is independently designated as C. 1-6 Alkyl, and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 Alkyl groups, and if multiple R groups are present 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

4. The compound of any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, wherein R 1 R 2a R 2b R 3 R 4 R 5 R 7a R 7b R 7c R 7d R 7e R 7f R 8 R 9a R 9b The optionally substituted 6- to 10-membered aromatic rings in rings Q and Z, the optionally substituted 5- to 10-membered aromatic heterocycles, the optionally substituted 6- to 10-membered divalent aromatic ring groups, the optionally substituted 5- to 10-membered divalent aromatic heterocycle groups, and the optionally substituted C 6-10 aryl, the optionally substituted 5- to 10-membered heteroaryl, the optionally substituted 4- to 10-membered non-aryl heterocyclic group, the optionally substituted C 1-6 Alkyl groups, the optionally substituted C 1-6 alkenyl, the optionally substituted C 1-6 alkynyl group, the optional substituted C 3-10 Alicyclic groups, the optionally substituted C 3-6 Cycloalkylene, the optionally substituted 4- to 6-membered divalent nonaryl heterocyclic group, the optionally substituted C 1-6 Alkylene, the optionally substituted C 3-10 Cycloalkylene, the optionally substituted 4- to 10-membered divalent nonaryl heterocyclic group, or the optionally substituted C-membered group 1-3 Each alkoxy group may be independently substituted by one to five identical or different substituents selected from the following: (1) Halogen atom, (2) Hydroxyl group, (3) Phenyl, (4) 5- to 6-heteroaryl compounds, (5) C atoms substituted with 1 to 3 halogen atoms 1-6 alkyl, (6) C 1-6 Alkoxy (7) C 3-7 Alicyclic groups, (8) 3- to 7-membered non-aryl heterocyclic groups, (9) -COR 10 , (10) -CO2R 10 , (11) -CONR 11 R 12 , (12) -NR 11 R 12 , (13) -SO2R 10 , (14) -SO2NR 11 R 12 ,and (15) Cyano group, R 10 If multiple cases exist, each is independently designated as C. 1-6 Alkyl, and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 Alkyl groups, and if multiple R groups are present 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

5. The compound of any one of claims 1 to 4, or a pharmaceutically acceptable salt thereof, wherein B is of the following formula (B-2), (B-3), or (B-4): [Chemical Formula 3] in Indicates the bonding position with the nitrogen atom on the hydantoin ring. 'a' represents 0, 1, or 2. b represents 1 or 2. R 8 C represents a hydrogen atom or an optional substitution. 1-6 Alkyl, and R 9a and R 9b Each C atom independently represents a hydrogen atom, a halogen atom, or an optionally substituted C atom. 1-6 alkyl.

6. The compound of any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof, wherein R 1 C atoms are optionally substituted with 1 to 3 fluorine atoms. 1-3 alkyl.

7. The compound of any one of claims 1 to 6, or a pharmaceutically acceptable salt thereof, wherein R 1 It is CF3.

8. The compound of any one of claims 1 to 7, or a pharmaceutically acceptable salt thereof, wherein R 3 C 6-10 Aryl (the aryl group is optionally replaced by 1 to 3 identical or different C atoms selected from halogen atoms and optionally substituted C atoms) 1-6 Alkyl substituents) or 5 to 10-membered heteroaryl groups (the heteroaryl group is optionally replaced by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

9. The compound of any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl, 4-(trifluoromethyl)phenyl or 4-fluoro-2-pyridyl.

10. The compound of any one of claims 1 to 9, or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl or 4-fluoro-2-pyridyl.

11. The compound of any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein ring Q is a 6- to 10-membered aromatic ring (the aromatic ring is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

12. The compound of any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein ring Q is a benzene ring (the benzene ring is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C). 1-6 Alkyl substituents).

13. The compound of any one of claims 1 to 12 or a pharmaceutically acceptable salt thereof, wherein a is 1 or 2.

14. The compound of any one of claims 1 to 13 or a pharmaceutically acceptable salt thereof, wherein a is 1.

15. The compound of any one of claims 1 to 14 or a pharmaceutically acceptable salt thereof, wherein b is 1.

16. The compound of any one of claims 1 to 15 or a pharmaceutically acceptable salt thereof, wherein a is 1 and b is 1.

17. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (2): [Chemical Formula 4] in A represents CHF or CH2. R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. Z represents -O-， 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Halogen atoms, hydroxyl group Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic group (the alicyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 Represents a hydrogen atom or a halogen atom. R 7b R 7c R 7d R 7e and R 7f Each represents independently hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

18. The compound of claim 17 or a pharmaceutically acceptable salt thereof, wherein A is CHF.

19. The compound of any one of claims 17 or 18, or a pharmaceutically acceptable salt thereof, wherein R 6 It is a hydrogen atom.

20. The compound of any one of claims 17 to 19 or a pharmaceutically acceptable salt thereof, wherein Z is 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

21. The compound of any one of claims 17 to 20, or a pharmaceutically acceptable salt thereof, wherein Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C... 1-6 Alkyl and -NR 11 R 12 (Substituents).

22. The compound of any one of claims 17 to 21, or a pharmaceutically acceptable salt thereof, wherein R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

23. The compound of any one of claims 17 to 22, or a pharmaceutically acceptable salt thereof, wherein R 5 for hydrogen atom, Halogen atoms, Cyano, -NR 7b R 7c , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

24. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is formula (3): [Chemical Formula 5] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

25. The compound of claim 24 or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl.

26. The compound of any one of claims 24 or 25, or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluoro-2-pyridyl.

27. The compound of any one of claims 24 to 26, or a pharmaceutically acceptable salt thereof, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

28. The compound of any one of claims 24 to 27 or a pharmaceutically acceptable salt thereof, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

29. The compound of any one of claims 24 to 28, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a nitrosobutyryl or piperidinyl group.

30. The compound of any one of claims 24 to 29, or a pharmaceutically acceptable salt thereof, wherein R 5 for C 1-6 alkyl, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

31. The compound of any one of claims 24 to 30, or a pharmaceutically acceptable salt thereof, wherein R 5 for C 1-3 alkyl, or 4 to 6-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

32. The compound of any one of claims 24 to 31, or a pharmaceutically acceptable salt thereof, wherein R 5 It is methyl.

33. The compound of any one of claims 24 to 31, or a pharmaceutically acceptable salt thereof, wherein R 5 It is an oxocyclic butyl group.

34. The compound of any one of claims 24 to 33, or a pharmaceutically acceptable salt thereof, wherein R 11 and R 12 It is a methyl group.

35. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is formula (4): [Chemical Formula 6] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

36. The compound of claim 35 or a pharmaceutically acceptable salt thereof, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

37. The compound of any one of claims 35 or 36, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

38. The compound of any one of claims 35 to 37, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a nitrosobutane.

39. The compound of any one of claims 35 to 38, or a pharmaceutically acceptable salt thereof, wherein R 5 for C 1-6 alkyl, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

40. The compound of any one of claims 35 to 39, or a pharmaceutically acceptable salt thereof, wherein R 5 for C 1-3 alkyl, or 4 to 6-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

41. The compound of any one of claims 35 to 40, or a pharmaceutically acceptable salt thereof, wherein R 5 It is an oxocyclic butyl group.

42. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (5): [Chemical Formula 7] in A represents CHF or CH2. R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. Z represents 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Halogen atoms, hydroxyl group Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-3 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic group (the alicyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 Represents a hydrogen atom or a halogen atom. R 7a R 7b R 7c R 7d R 7e and R 7f Each represents independently hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 8 express hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

43. The compound of claim 42 or a pharmaceutically acceptable salt thereof, wherein A is CHF.

44. The compound of any one of claims 42 or 43, or a pharmaceutically acceptable salt thereof, wherein R 6 It is a hydrogen atom.

45. The compound of any one of claims 42 to 44 or a pharmaceutically acceptable salt thereof, wherein Z is 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

46. ​​The compound of any one of claims 42 to 45 or a pharmaceutically acceptable salt thereof, wherein Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C... 1-6 Alkyl and -NR 11 R 12 (Substituents).

47. The compound of any one of claims 42 to 46, or a pharmaceutically acceptable salt thereof, wherein R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

48. The compound of any one of claims 42 to 47, or a pharmaceutically acceptable salt thereof, wherein... R 5 for hydrogen atom, hydroxyl group Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic group (the alicyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 7d C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

49. The compound of any one of claims 42 to 48, or a pharmaceutically acceptable salt thereof, wherein R 8 C 1-6 alkyl.

50. The compound of any one of claims 42 to 49, or a pharmaceutically acceptable salt thereof, wherein R 8 It is a methyl group.

51. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (6): [Chemical Formula 8] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, hydroxyl group Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic group (the alicyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

52. The compound of claim 51 or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl.

53. The compound of any one of claims 51 or 52, or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluoro-2-pyridyl.

54. The compound of any one of claims 51 to 53, or a pharmaceutically acceptable salt thereof, wherein R 4 for Single key, or C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

55. The compound of any one of claims 51 to 54, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a single key.

56. The compound of any one of claims 51 to 54, or a pharmaceutically acceptable salt thereof, wherein R 4 C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

57. The compound of any one of claims 51 to 56, or a pharmaceutically acceptable salt thereof, wherein R 5 for hydroxyl group Cyano, C 1-6 alkyl, C 3-10 Alicyclic groups, or 4 to 10-membered non-aryl heterocyclic groups.

58. The compound of any one of claims 51 to 57 or a pharmaceutically acceptable salt thereof, wherein R 5 It is a methyl group.

59. The compound of any one of claims 51 to 57 or a pharmaceutically acceptable salt thereof, wherein R 5 It is an oxocyclic butyl group.

60. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (7): [Chemical Formula 9] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Cyano, C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

61. The compound of claim 60 or a pharmaceutically acceptable salt thereof, wherein R 4 for Single key, or C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

62. The compound of any one of claims 60 or 61, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a single key.

63. The compound of any one of claims 60 to 62, or a pharmaceutically acceptable salt thereof, wherein R 4 C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents).

64. The compound of any one of claims 60 to 63, or a pharmaceutically acceptable salt thereof, wherein R 5 for C 1-6 alkyl, or Cyano group.

65. The compound of any one of claims 60 to 64, or a pharmaceutically acceptable salt thereof, wherein R 5 It is a methyl group.

66. The compound of any one of claims 60 to 64, or a pharmaceutically acceptable salt thereof, wherein R 5 It is a cyano group.

67. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is formula (8): [Chemical Formula 10] in A represents CHF or CH2. R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. Z represents 6 to 10-membered divalent aromatic ring groups (the divalent aromatic ring groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), C 3-10 Cycloalkylene groups (the cycloalkylene groups are optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Halogen atoms, hydroxyl group Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkenyl (the alkenyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-6 Alkyne group (the alkynyl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 1-3 Alkoxy groups (the alkoxy groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic group (the alicyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) C 6-10 Aryl (the aryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) 5 to 10-membered heteroaryl (the heteroaryl group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 6 Represents a hydrogen atom or a halogen atom. R 7a R 7b R 7c R 7d R 7e and R 7f Each represents independently hydrogen atom, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), R 9a and R 9b Each represents independently hydrogen atom, Halogen atoms, or C 1-6 Alkyl groups (the alkyl group optionally consisting of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

68. The compound of claim 67 or a pharmaceutically acceptable salt thereof, wherein A is CHF.

69. The compound of any one of claims 67 or 68, or a pharmaceutically acceptable salt thereof, wherein R 6 It is a hydrogen atom.

70. The compound of any one of claims 67 to 69 or a pharmaceutically acceptable salt thereof, wherein Z is 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 5 to 10-membered divalent aromatic heterocyclic groups (the divalent aromatic heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

71. The compound of any one of claims 67 to 70 or a pharmaceutically acceptable salt thereof, wherein Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C... 1-6 Alkyl and -NR 11 R 12 (Substituents).

72. The compound of any one of claims 67 to 71, or a pharmaceutically acceptable salt thereof, wherein R 4 for single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent nonaryl heterocyclic groups (the divalent nonaryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

73. The compound of any one of claims 67 to 72 or a pharmaceutically acceptable salt thereof, wherein R 5 for hydrogen atom, Cyano, -NR 7b R 7c , C 1-6 Alkyl groups (the alkyl group may optionally be composed of 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 (substituents) C 3-10 Alicyclic group (the alicyclic group is optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituent substitution), or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (Substituents).

74. The compound of any one of claims 67 to 73 or a pharmaceutically acceptable salt thereof, wherein R 9a and R 9b It is a fluorine atom.

75. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (9): [Chemical Formula 11] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Cyano, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 acetylenic group, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

76. The compound of claim 75 or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluorophenyl.

77. The compound of any one of claims 75 or 76, or a pharmaceutically acceptable salt thereof, wherein R 3 It is 4-fluoro-2-pyridyl.

78. The compound of any one of claims 75 to 77, or a pharmaceutically acceptable salt thereof, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

79. The compound of any one of claims 75 to 78 or a pharmaceutically acceptable salt thereof, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

80. The compound of any one of claims 75 to 79 or a pharmaceutically acceptable salt thereof, wherein R 4 It is a nitrosobutane.

81. The compound of any one of claims 75 to 80, or a pharmaceutically acceptable salt thereof, wherein R 5 It is a 4- to 10-membered non-aryl heterocyclic group.

82. The compound of any one of claims 75 to 81, or a pharmaceutically acceptable salt thereof, wherein R 5 It is a 4- to 6-membered non-aryl heterocyclic group.

83. The compound of any one of claims 75 to 82, or a pharmaceutically acceptable salt thereof, wherein R 5 It is an oxocyclic butyl group.

84. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein formula (1) is the following formula (10): [Chemical Formula 12] in R 3 It represents 4-fluorophenyl or 4-fluoro-2-pyridyl. R 4 express single bond, C 1-6 Alkylenes (the alkylene group is optionally composed of 1 to 3 identical or different atoms selected from halogen atoms and C) 1-6 Alkyl substituents), or 4 to 10-membered divalent non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents) R 5 express hydrogen atom, Cyano, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 acetylenic group, or 4 to 10-membered non-aryl heterocyclic groups (the non-aryl heterocyclic groups are optionally surrounded by 1 to 3 identical or different atoms selected from halogen atoms, C 1-6 Alkyl and -NR 11 R 12 (substituents), and R 11 and R 12 Each independently represents a hydrogen atom or a carbon atom. 1-6 alkyl, And if there are multiple R 11 Or R 12 In the case of R 11 Or R 12 Each of them can be the same or different, where R connected to the same nitrogen atom 11 and R 12 Both are C 1-6 When alkyl, together with the nitrogen atom to which they are attached, they can form 3 to 8-membered nitrogen-containing non-aryl heterocyclic groups.

85. The compound of claim 84 or a pharmaceutically acceptable salt thereof, wherein R 4 It consists of 4 to 10-membered divalent non-aryl heterocyclic groups.

86. The compound of any one of claims 84 or 85, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a 4 to 6-membered divalent non-aryl heterocyclic group.

87. The compound of any one of claims 84 to 86, or a pharmaceutically acceptable salt thereof, wherein R 4 It is a nitrosobutane.

88. The compound of any one of claims 84 to 87, or a pharmaceutically acceptable salt thereof, wherein R 5 It is a 4- to 10-membered non-aryl heterocyclic group.

89. The compound of any one of claims 84 to 88, or a pharmaceutically acceptable salt thereof, wherein R 5 It is a 4- to 6-membered non-aryl heterocyclic group.

90. The compound of any one of claims 84 to 89, or a pharmaceutically acceptable salt thereof, wherein R 5 It is an oxocyclic butyl group.

91. The compound of claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of: N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide, 2-[(1'S)-5'-{1-[(3-fluoro-1-methylazacyclobutane-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)azacyclobutan-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]acetamide, N-[(5-fluoropyridin-2-yl)methyl]-2-[(1'S)-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)azacyclobutan-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(5-fluoropyridin-2-yl)methyl]-2-[(1'S)-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxetane-3-yl)azacyclobutane-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-5'-[1-(2-cyanopropyl-2-yl)-1H-pyrazol-4-yl]-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S)-5'-[1-(2-cyanopropyl-2-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(5-methyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-3-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(5-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S)-5'-(5-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(3-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S)-5'-(3-fluoro-1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-5'-[1-(oxacyclohexane-4-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, N-[(5-fluoropyridin-2-yl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-5'-(1-{[3-(dimethylamino)oxetane-3-yl]methyl}-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)piperidin-4-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-5'-[1-(oxecyclobutan-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutan-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-{1-[(oxecyclobutan-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutan-3-yl]acetamide, 2-{(1'S,3'R)-5'-[1-(2-cyanopropyl-2-yl)-1H-pyrazol-4-yl]-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-5'-[1-(1-hydroxy-2-methylpropyl-2-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'R,3'S)-3',6'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3',6'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-5'-(1-cyclobutyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, and 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]-N-{[4-(trifluoromethyl)phenyl]methyl}acetamide.

92. The compound of claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of: 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)azacyclobutan-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-{1-[1-(oxecyclobutan-3-yl)piperidin-4-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[3-(trifluoromethyl)oxecyclobutan-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-5'-[1-(oxecyclobutan-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutan-3-yl]acetamide, 2-[(1'S,3'R)-3'-fluoro-5'-{1-[(oxecyclobutan-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutan-3-yl]acetamide, 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-[(1'S,3'R)-5'-(1-ethyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, 2-{(1'S,3'R)-3'-fluoro-2,5-dioxo-5'-[1-(prop-2-yl)-1H-pyrazol-4-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide, and 2-[(1'S,3'R)-5'-(1-cyclobutyl-1H-pyrazol-4-yl)-3'-fluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl]-N-[(5-fluoropyridin-2-yl)methyl]-N-[1-methyl-3-(trifluoromethyl)azacyclobutane-3-yl]acetamide.

93. A medicament comprising, as an active ingredient, any one of claims 1 to 92, a compound or a pharmaceutically acceptable salt thereof.

94. A pharmaceutical composition comprising the compound of any one of claims 1 to 92 or a pharmaceutically acceptable salt thereof.

95. A therapeutic and / or preventive agent for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disease, comprising the compound of any one of claims 1 to 92 or a pharmaceutically acceptable salt thereof as the active ingredient.

96. A therapeutic and / or preventive agent for cancer, comprising the compound of any one of claims 1 to 92 or a pharmaceutically acceptable salt thereof as an active ingredient.

97. The therapeutic and / or preventive agent of claim 95 or 96, wherein the cancer is at least one type of cancer selected from SMARC-deficient cancer, SS18-SSX fusion cancer, and ARID-deficient cancer.

98. The therapeutic and / or preventive agent according to any one of claims 95 to 97, wherein the cancer is selected from malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordal meningioma, neuroepithelial tumor, glial neuron tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraosseous myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, basal squamous cell carcinoma of the sinuses, esophageal cancer, papillary thyroid carcinoma, follicular thyroid carcinoma, gastrointestinal stromal tumor, undifferentiated rhabdoid tumor of the pancreas, gastrointestinal rhabdoid tumor, renal medullary carcinoma, endometrial cancer, vulvar stromal tumor. At least one type of cancer among the following: epithelioid tumors, colon cancer, mesothelioma, lung adenocarcinoma, large cell lung cancer, pulmonary neuroendocrine tumor, gastroesophageal junction cancer, gastric cancer, bladder cancer, lung squamous cell carcinoma, pancreatic cancer, medulloblastoma, renal clear cell carcinoma, liver cancer, pleomorphic carcinoma, thoracic sarcoma, ovarian small cell carcinoma, primary gallbladder tumor, uterine sarcoma, ovarian granulosa cell tumor, adrenocortical carcinoma, small cell lung cancer, ovarian cancer, uterine cancer, neuroblastoma, mucinous ovarian tumor, nasal cavity and sinus cancer, intrathoracic sarcoma, bile duct cancer, neuroblastoma, melanoma, breast cancer, undifferentiated round cell sarcoma, rhabdomyosarcoma, and Ewing sarcoma.

99. A method for treating and / or preventing cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disease, comprising administering to a patient in need a therapeutically effective amount and / or a preventively effective amount of the compound of any one of claims 1 to 92 or a pharmaceutically acceptable salt thereof.

100. Use of any compound of claims 1 to 92 or a pharmaceutically acceptable salt thereof in the manufacture of a therapeutic and / or preventative agent for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disease.

101. The compound of any one of claims 1 to 92 or a pharmaceutically acceptable salt thereof, for the treatment and / or prevention of cancer, non-alcoholic fatty liver disease (NAFLD), acute liver disease, heart disease, or metabolic disease.

102. The compound or a pharmaceutically acceptable salt thereof of any one of claims 1 to 92, used in combination with another drug or a pharmaceutically acceptable salt thereof for treating cancer, wherein the other drug is at least one selected from drugs such as hormone therapy agents, chemotherapy agents, immunotherapy agents, and agents that inhibit the action of cell growth factors and their receptors.

103. A pharmaceutical composition comprising the compound of any one of claims 1 to 92 or a pharmaceutically acceptable salt thereof, configured to be combined with another drug, wherein the other drug is at least one selected from drugs such as hormone therapy agents, chemotherapeutic agents, immunotherapy agents, and agents that inhibit the action of cell growth factors and their receptors.

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