Tertiary amide derivative substituted by quaternary carbon

Abstract

To provide a tertiary amide derivative substituted by a quaternary carbon that is useful as a medicine, and a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising these, or a therapeutic or prophylactic agent for a disease condition in which CBP / P300 is involved, comprising the compositions.SOLUTION: A compound is represented by the following general formula (1) [where A represents CR6aR6b, C=O, C=CH2, or S(=O)2; the ring Q represents an optionally substituted 6- to 10-membered aromatic hydrocarbon ring or an optionally substituted 5- to 10-membered aromatic heterocyclic ring; and Z represents -O-, -N(R7a)-, an optionally substituted 6- to 10-membered bivalent aromatic ring group, an optionally substituted 5- to 10-membered bivalent aromatic heterocyclic ring group, or an optionally substituted 4- to 10-membered bivalent non-aryl heterocyclic ring group] or a pharmaceutically acceptable salt thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present disclosure relates to tertiary amide derivatives substituted with a quaternary carbon that are useful as pharmaceuticals, pharmaceutically acceptable salts thereof, pharmaceutical compositions containing them, or therapeutic or preventive agents for pathologies involving CBP / P300 that contain these compositions. [Background technology]

[0002] Chromosomes dynamically control gene replication and transcription by changing their higher-order structure through methylation of their constituent DNA and various modifications (acetylation, methylation, phosphorylation, ubiquitination, etc.) of their histones (histones H2A, H2B, H3, H4) (Non-patent document 1).

[0003] Histone acetylation is a common post-translational modification in eukaryotes, promoting gene transcription. Histone acetyltransferases (HATs), which function in histone acetylation, are enzymes that transfer acetyl groups to the lysine side chains of histones. They are broadly classified into four groups based on amino acid sequence homology, higher-order structure, and function: CBP / P300 (E1A binding protein p300 / CREB), These are GCN5 / PCAF (general control nonrepressed-protein 5 / P300 / CBP-associated factor), 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 over 90% amino acid sequence identity and contain a HAT domain, as well as CH1 / CH2 / CH3 (cysteine-histidine-rich) domains, a KIX domain, and a bromodomain (Non-Patent Document 2).

[0004] CBP / P300 were discovered as binding partners of E1A adenoviral protein and cAMP-regulated enhancer binding protein, respectively (Non-patent Documents 3-5). Subsequently, it was found that CBP / P300 has HAT activity (Non-patent Documents 6 and 7), and its substrate specificity was also investigated. In addition to lysine residues of histones (H2A, H2B, H3, and H4), it was found to bind to p53 (Non-patent Document 8), MyoD (Non-patent Document 9), STAT3 (Non-patent Document 10), and Androgen It has been reported that CBP / P300 also acetylates receptors (Non-Patent Document 11). CBP / P300 is also involved in numerous biological reactions such as division, proliferation, and differentiation (Non-Patent Document 12).

[0005] CBP / P300 has been reported to play an important role in the proliferation of various cancers, including prostate cancer (Non-Patent Documents 13 and 14), liver cancer (Non-Patent Documents 15 and 16), lung cancer (Non-Patent Documents 17, 18, and 19), breast cancer (Non-Patent Document 20), colorectal cancer and gastric cancer (Non-Patent Document 21), hematological cancer (Non-Patent Documents 22 and 23), pancreatic cancer (Non-Patent Document 24), bladder cancer (Non-Patent Document 25), gastrointestinal stromal tumor (Non-Patent Document 26), NUT midline carcinoma (Non-Patent Document 27), ovarian cancer (Non-Patent Document 28), malignant rhabdoid tumor, and epithelioid sarcoma (Patent Document 11).

[0006] For these reasons, drugs that inhibit the function of CBP / P300 are expected to be useful as antitumor agents. To date, Patent Documents 1 to 10 and Non-Patent Document 29 have disclosed small molecule inhibitors that target the HAT domain of CBP / P300. [Prior art documents] [Patent documents]

[0007] [Patent Document 1] International Publication No. 2016 / 044770 [Patent Document 2] International Publication No. 2018 / 235966 [Patent Document 3] International Publication No. 2019 / 111980 [Patent Document 4] International Publication No. 2019 / 049061 [Patent Document 5] International Publication No. 2019 / 161157 [Patent Document 6] International Publication No. 2019 / 161162 [Patent Document 7] International Publication No. 2020 / 176558 [Patent Document 8] International Publication No. 2019 / 201291 [Patent Document 9] International Publication No. 2020 / 108500 [Patent Document 10] International Publication No. 2020 / 198567 [Patent Document 11] International Publication No. 2022 / 138944 [Non-patent literature]

[0008] [Non-Patent Document 1] Genes Dev.2002,16(14):1739-1742. [Non-patent document 2] Mol Genet Metab.2016,119(1-2):37-43. [Non-patent document 3] Virology.1985,147(1):142-153. [Non-patent document 4] Mol Cell Biol.1986,6(5):1579-158 9. [Non-Patent Document 5] Nature.1993,365(6449):855-859. [Non-patent document 6] Cell.1996,87(5):953-959. [Non-Patent Document 7] Nature.1996,384(6610):641-643.

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[0009] The present disclosure provides compounds that exert anticancer effects by inhibiting CBP / P300, which has been reported to be overexpressed, mutated, or hyperactive in various cancers. Preferably, the present disclosure provides compounds that have high CBP / P300 inhibitory activity, as well as "high water solubility that exerts anticancer effects upon intravenous administration" and "high oral absorbability that exerts anticancer effects upon oral administration." In other words, the present disclosure provides compounds that are extremely useful as anticancer agents that can be expected to be applied to the treatment of a wide range of cancer types.

[0010] As a result of extensive research, the present inventors have found that a compound represented by the following formula (1) or a pharmaceutically acceptable salt thereof (hereinafter, sometimes referred to as "the compound of the present disclosure") exhibits excellent anticancer activity due to its strong inhibitory effect on the HAT domain of CBP / P300, and also exhibits high oral absorbability and water solubility suitable for oral and intravenous administration, thereby completing the present disclosure.

[0011] That is, the present disclosure is as follows.

[0012] [Section 1] [ka] [In the formula, A is CR 6a R 6b , C=O, C=CH2, or S(=O)2; B is represented by the following formula (B-1): [ka] [wherein * represents the bonding position to the nitrogen atom of 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 is -O-, -N(R 7a )-, an optionally substituted 6- to 10-membered divalent aromatic ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, or an optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, R 1 may be substituted C 1-6 Alkyl or optionally substituted C 3-10 represents an alicyclic group, R 2a and R 2b each independently represents an optionally substituted C 1-6 represents alkyl, where R 2a and R 2btogether with the carbon atom to which they are attached, may be substituted C 3-6 It may form a cycloalkylene or an optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, R 3 may be substituted C 6-10 Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted C 3-10 represents an alicyclic group or an optionally substituted 4- to 10-membered non-aryl heterocyclic group, R 4 is a single bond, optionally substituted C 1-6 Alkylene, optionally substituted C 3-10 represents a cycloalkylene or an optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, R 5 is a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkenyl, optionally substituted C 1-6 Alkynyl, optionally substituted C 1-3 Alkoxy, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , optionally substituted C 3-10 an alicyclic group, an optionally substituted 4- to 10-membered non-aryl heterocyclic group, an optionally substituted C 6-10 aryl, or an optionally substituted 5- to 10-membered heteroaryl; R 6a and R 6b are each independently a hydrogen atom, a fluorine atom, or an optionally substituted C 1-6 Alkyl or optionally substituted C 1-3 represents alkoxy, where R 6a and R 6b together with the carbon atom to which they are attached, may be substituted C 3-6 may form a cycloalkylene or an optionally substituted 4- to 6-membered divalent non-aryl heterocycle, R 7a , R 7b , R 7c , R 7d , R 7e , R 7f are each independently a hydrogen atom or an optionally substituted C 1-6 represents alkyl] or a pharmaceutically acceptable salt thereof. [Section 2] R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6a , R 6b , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 8 , R 9a , R 9b , an optionally substituted 6- to 10-membered aromatic hydrocarbon ring, an optionally substituted 5- to 10-membered aromatic heterocyclic ring, an optionally substituted 6- to 10-membered divalent aromatic hydrocarbon ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, an optionally substituted C 6-10 Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 a alkenyl, optionally substituted C 1-6 Alkynyl, optionally substituted C 3-10 Alicyclic groups, optionally substituted C 3-6 Cycloalkylene, optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, optionally substituted C 1-6 Alkylene, optionally substituted C 3-10 Cycloalkylene, optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, optionally substituted C 1-3 Each alkoxy is independently (1) a halogen atom, (2) hydroxyl group, (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, (8) C 1-6 Alkoxy, (9) C 1-6 Alkylthio (10)C 3-10 alicyclic group, (11) a 3- to 10-membered non-aryl heterocyclic group, (12) carboxyl, (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) sulfonic acids, (28) Phosphoric acid, (29) cyano, and (30) Nitro may be substituted with 1 to 5 identical or different substituents selected from the group consisting of Here, the above (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, (8)C 1-6 Alkoxy, (9)C 1-6 Alkylthio, (10)C 3-10 The alicyclic group and the group shown in (11) 3- to 10-membered non-aryl heterocyclic group are (a) a halogen atom, (b) hydroxyl group, (c)C 6-10 aryl, (d) 5- to 12-membered heteroaryl, (e)C 1-6 Alkyl, (f)C 2-6 alkenyl, (g)C 2-6 Alkynyl, (h)C 1-6 Alkoxy, (I C 3-10 alicyclic group, (j) a 3- to 10-membered non-aryl heterocyclic group, (k) carboxyl, (l)-COR 10 , (m)-CO2R 10 , (n)-CONR 11 R 12 , (o)-NR 11 R 12 , (p)-NR 13 COR 10 , (q)-NR 13 SO2R10 , (r)-SO2R 10 , (s)-SO2NR 11 R 12 , (t) sulfonic acids, (u) phosphoric acid, (v) cyano, and (w) Nitro may be substituted with 1 to 5 identical or different substituents selected from the group consisting of R 10 However, if there are multiple, each is independently C 1-6 is alkyl, R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, and R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be bonded together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle, R 13 is a hydrogen atom or C 1-6 is alkyl, Item 1. The compound according to item 1, or a pharmaceutically acceptable salt thereof. [Section 3] R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6a , R 6b , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 8 , R 9a , R 9b, an optionally substituted 6- to 10-membered aromatic hydrocarbon ring, an optionally substituted 5- to 10-membered aromatic heterocyclic ring, an optionally substituted 6- to 10-membered divalent aromatic hydrocarbon ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, an optionally substituted C 6-10 Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkenyl, optionally substituted C 1-6 Alkynyl, optionally substituted C 3-10 Alicyclic groups, optionally substituted C 3-6 Cycloalkylene, optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, optionally substituted C 1-6 Alkylene, optionally substituted C 3-10 Cycloalkylene, optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, optionally substituted C 1-3 Each alkoxy is independently (1) a halogen atom, (2) hydroxyl group, (3) C 6-10 aryl, (4) 5- to 12-membered heteroaryl, (5) C optionally substituted with 1 to 3 halogen atoms 1-6 Alkyl, (6) C 2-6 alkenyl, (7) C 2-6 Alkynyl, (8) C 1-6 Alkoxy, (9) C 3-10 alicyclic group, (10) a 3- to 10-membered non-aryl heterocyclic group, (11) carboxyl, (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) sulfonic acids, (19) Phosphoric acid, (20) cyano, and (21) Nitro may be substituted with 1 to 5 identical or different substituents selected from the group consisting of R 10 However, if there are multiple, each is independently C 1-6 is alkyl, R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, and R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be joined together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle; Item 3. The compound according to any one of Items 1 and 2, or a pharmaceutically acceptable salt thereof. [Section 4] R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6a , R 6b , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 8 , R 9a , R 9b, an optionally substituted 6- to 10-membered aromatic hydrocarbon ring, an optionally substituted 5- to 10-membered aromatic heterocyclic ring, an optionally substituted 6- to 10-membered divalent aromatic hydrocarbon ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, an optionally substituted C 6-10 Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkenyl, optionally substituted C 1-6 Alkynyl, optionally substituted C 3-10 Alicyclic groups, optionally substituted C 3-6 Cycloalkylene, optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, optionally substituted C 1-6 Alkylene, optionally substituted C 3-10 Cycloalkylene, optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, optionally substituted C 1-3 Each alkoxy is independently (1) a halogen atom, (2) hydroxyl group, (3) phenyl, (4) 5-6 membered heteroaryl, (5) C optionally substituted with 1 to 3 halogen atoms 1-6 Alkyl, (6) C 1-6 Alkoxy, (7) C 3-7 alicyclic group, (8) a 3- to 7-membered non-aryl heterocyclic group, (9)-COR 10 , (10)-CO2R 10 , (11)-CONR 11 R 12 , (12)-NR 11 R 12 , (13)-SO2R 10 , (14)-SO2NR 11 R12 , and (15) Cyano may be substituted with 1 to 5 identical or different substituents selected from the group consisting of R 10 However, if there are multiple, each is independently C 1-6 is alkyl, R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, and R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be joined together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle; Item 4. The compound according to any one of Items 1 to 3, or a pharmaceutically acceptable salt thereof. [Section 5] R 6a and R 6b are each independently a fluorine atom or a methyl group; Item 5. The compound according to any one of Items 1 to 4, or a pharmaceutically acceptable salt thereof. [Section 6] R 6a and R 6b is a fluorine atom, Item 6. The compound according to any one of Items 1 to 5, or a pharmaceutically acceptable salt thereof. [Section 7] A is CF2, C(F)CH3, or C=O; Item 7. The compound according to any one of Items 1 to 6, or a pharmaceutically acceptable salt thereof. [Section 8] A is CF2 or C=O; Item 8. The compound according to any one of Items 1 to 7, or a pharmaceutically acceptable salt thereof. [Section 9] B is represented by the following formula (B-2), (B-3), or (B-4): [ka] [wherein * represents the bonding position to the nitrogen atom of the hydantoin ring, a represents 0, 1, or 2; b represents 1 or 2; R 8 is a hydrogen atom or an optionally substituted C 1-6 represents alkyl, R 9a and R 9b are each independently a hydrogen atom, a halogen atom, or an optionally substituted C 1-6 represents alkyl], Item 9. The compound according to any one of Items 1 to 8, or a pharmaceutically acceptable salt thereof. [Section 10] R 1 C optionally substituted with 1 to 3 fluorines 1-3 is alkyl, Item 10. The compound according to any one of Items 1 to 9, or a pharmaceutically acceptable salt thereof. [Section 11] R 1 But it is CF3. Item 11. The compound according to any one of Items 1 to 10, or a pharmaceutically acceptable salt thereof. [Section 12] R 3 But C 6-10 Aryl (the aryl is a halogen atom and C 1-6 12. The compound according to any one of items 1 to 11, or a pharmaceutically acceptable salt thereof, wherein R is 1 to 3, and ... [Section 13] R 3 is 4-fluorophenyl; Item 13. The compound according to any one of Items 1 to 12, or a pharmaceutically acceptable salt thereof. [Section 14] Ring Q is a 6- to 10-membered aromatic hydrocarbon ring (the aromatic hydrocarbon ring is not substituted with a halogen atom or C 1-6alkyl), Item 14. The compound according to any one of Items 1 to 13, or a pharmaceutically acceptable salt thereof. [Section 15] Ring Q is benzene. Item 15. The compound according to any one of Items 1 to 14, or a pharmaceutically acceptable salt thereof. [Section 16] a is 1 or 2; Item 16. The compound according to any one of Items 1 to 15, or a pharmaceutically acceptable salt thereof. [Section 17] a is 1, Item 17. The compound according to any one of Items 1 to 16, or a pharmaceutically acceptable salt thereof. [Section 18] b is 1, Item 18. The compound according to any one of Items 1 to 17, or a pharmaceutically acceptable salt thereof. [Section 19] Equation (1) is changed to the following equation (2): [ka] [In the formula, A represents CF2 or C=O; Z is -O-, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and --NR11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 teeth, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 teeth, hydrogen atoms, halogen atoms, hydroxyl groups, Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkenyl (the alkenyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkynyl (the alkynyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 6-10 Aryl (the aryl is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5-10 membered heteroaryl (the heteroaryl is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7b , R 7c , R 7d , R 7e , R 7f are each independently a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. That is, Item 1. The compound according to item 1 or a pharmaceutically acceptable salt thereof. [Section 20] A is CF2, Item 20. The compound according to any one of Items 1 to 19, or a pharmaceutically acceptable salt thereof. [Section 21] Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 a Rukil and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 21. The compound according to any one of items 1 to 20, or a pharmaceutically acceptable salt thereof. [Section 22] Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 22. The compound according to any one of items 1 to 21, or a pharmaceutically acceptable salt thereof. [Section 23] R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 23. The compound according to any one of items 1 to 22, or a pharmaceutically acceptable salt thereof. [Section 24] R 5 but, hydrogen atoms, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 24. The compound according to any one of items 1 to 23, or a pharmaceutically acceptable salt thereof. [Section 25] Equation (1) is changed to the following equation (3): [ka] [In the formula, R 4 teeth, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 teeth, hydrogen atoms, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7b , R 7c are each independently a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. Item 1. The compound according to item 1 or a pharmaceutically acceptable salt thereof. [Section 26] R 4 but, a 4- to 10-membered divalent non-aryl heterocyclic group; 26. The compound according to any one of items 1 to 25, or a pharmaceutically acceptable salt thereof. [Section 27] R 4 but, a 4- to 6-membered divalent non-aryl heterocyclic group; 27. The compound according to any one of items 1 to 26, or a pharmaceutically acceptable salt thereof. [Section 28] R 4 but, azetidinylene, 28. The compound according to any one of items 1 to 27, or a pharmaceutically acceptable salt thereof. [Section 29] R 5 but, C 1-6 alkyl, or 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not substituted by a halogen atom or a C 1-6 and (optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of alkyl, Item 29. The compound according to any one of Items 1 to 28, or a pharmaceutically acceptable salt thereof. [Section 30] R 5 but, C 1-3 alkyl, or 4- to 6-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not substituted with a halogen atom or C 1-6 and (optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of alkyl, Item 30. The compound according to any one of Items 1 to 29, or a pharmaceutically acceptable salt thereof. [Section 31] R 5 but, is methyl, 31. The compound according to any one of items 1 to 30, or a pharmaceutically acceptable salt thereof. [Section 32] R 5 but, oxetanyl, 31. The compound according to any one of items 1 to 30, or a pharmaceutically acceptable salt thereof. [Section 33] Equation (1) is changed to the following equation (4): [ka] [In the formula, A represents CF2 or C=O; Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and --NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 teeth, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 teeth, hydrogen atoms, halogen atoms, hydroxyl groups, Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkenyl (the alkenyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkynyl (the alkynyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-3 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 6-10 Aryl (the aryl is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5-10 membered heteroaryl (the heteroaryl is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7a , R7b , R 7c , R 7d , R 7e , R 7f are each independently a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 8 teeth, a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. That is, Item 1. The compound according to item 1 or a pharmaceutically acceptable salt thereof. [Section 34] A is CF2, 34. The compound according to any one of items 1 to 33, or a pharmaceutically acceptable salt thereof. [Section 35] Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 35. The compound according to any one of items 1 to 34, or a pharmaceutically acceptable salt thereof. [Section 36] Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 36. The compound according to any one of items 1 to 35, or a pharmaceutically acceptable salt thereof. [Section 37] R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), 37. The compound according to any one of items 1 to 36, or a pharmaceutically acceptable salt thereof. [Section 38] R 5 but, hydrogen atoms, Cyano, C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of Item 38. The compound according to any one of Items 1 to 37, or a pharmaceutically acceptable salt thereof. [Section 39] R 8 but, C 1-6 is alkyl, Item 39. The compound according to any one of Items 1 to 38, or a pharmaceutically acceptable salt thereof. [Section 40] Equation (1) is changed to the following equation (5): [ka] [In the formula, R 4 teeth, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 teeth, hydrogen atoms, Cyano, C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of -SO2R 7d , -CONR 7e R 7f , or 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7d , R 7e , R 7f are each independently a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. Item 1. The compound according to item 1 or a pharmaceutically acceptable salt thereof. [Section 41] R 4 but, a single bond, or C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), 41. The compound according to any one of items 1 to 40, or a pharmaceutically acceptable salt thereof. [Section 42] R 4 is a single bond, 42. The compound according to any one of items 1 to 41, or a pharmaceutically acceptable salt thereof. [Section 43] R 4 But C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), 43. The compound according to any one of items 1 to 42, or a pharmaceutically acceptable salt thereof. [Section 44] R 5 but, C 1-6 alkyl, or It is cyano, 44. The compound according to any one of items 1 to 43, or a pharmaceutically acceptable salt thereof. [Section 45] R 5 but, is a methyl group, 45. The compound according to any one of items 1 to 44, or a pharmaceutically acceptable salt thereof. [Section 46] R 5 but, It is cyano, 45. The compound according to any one of items 1 to 44, or a pharmaceutically acceptable salt thereof. [Section 47] Equation (1) is changed to the following equation (6): [ka] [In the formula, A represents CF2 or C=O; Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and --NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 teeth, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 teeth, hydrogen atoms, halogen atoms, hydroxyl groups, Cyano, -NR 7b R 7c , -SO2R 7d , -CONR 7e R 7f , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 and substituted with 1 to 3 identical or different substituents selected from the group consisting of (also acceptable), C 1-6 Alkenyl (the alkenyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkynyl (the alkynyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-3 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 6-10 Aryl (the aryl is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5-10 membered heteroaryl (the heteroaryl is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7a , R7b , R 7c , R 7d , R 7e , R 7f are each independently a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 9a and R 9b are each independently hydrogen atoms, a halogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be joined together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. ] Item 1. The compound according to item 1 or a pharmaceutically acceptable salt thereof. [Section 48] A is CF2, Item 48. The compound according to any one of Items 1 to 47, or a pharmaceutically acceptable salt thereof. [Section 49] Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of Item 49. The compound according to any one of Items 1 to 48, or a pharmaceutically acceptable salt thereof. [Section 50] Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of Item 50. The compound according to any one of Items 1 to 49, or a pharmaceutically acceptable salt thereof. [Section 51] R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 51. The compound according to any one of items 1 to 50, or a pharmaceutically acceptable salt thereof. [Section 52] R 5 but, hydrogen atoms, Cyano, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of 52. The compound according to any one of items 1 to 51, or a pharmaceutically acceptable salt thereof. [Section 53] R 9a and R 9b but, is a fluorine atom, 53. The compound according to any one of items 1 to 52, or a pharmaceutically acceptable salt thereof. [Section 54] Equation (1) is changed to the following equation (7): [ka] [In the formula, R 4 teeth, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 teeth, hydrogen atoms, Cyano, C 1-6 Alkyl, C 1-6 alkenyl, C 1-6 alkynyl, or 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 11 and R 12 are each independently a hydrogen atom or C 1-6 represents alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. Item 1. The compound according to item 1 or a pharmaceutically acceptable salt thereof. [Section 55] R 4 but, a 4- to 10-membered divalent non-aryl heterocyclic group; 55. The compound according to any one of items 1 to 54, or a pharmaceutically acceptable salt thereof. [Section 56] R 4 but, a 4- to 6-membered divalent non-aryl heterocyclic group; 56. The compound according to any one of items 1 to 55, or a pharmaceutically acceptable salt thereof. [Section 57] R 4 but, azetidinylene, 57. The compound according to any one of items 1 to 56, or a pharmaceutically acceptable salt thereof. [Section 58] R 5 but, C 1-6 alkyl, or a 4- to 10-membered non-aryl heterocyclic group; Item 58. The compound according to any one of Items 1 to 57, or a pharmaceutically acceptable salt thereof. [Section 59] R 5 but, C 1-3 alkyl, or a 4- to 6-membered non-aryl heterocyclic group; Item 59. The compound according to any one of Items 1 to 58, or a pharmaceutically acceptable salt thereof. [Section 60] R 5 but, is methyl, Item 60. The compound according to any one of Items 1 to 59, or a pharmaceutically acceptable salt thereof. [Section 61] R 5 but, oxetanyl, Item 60. The compound according to any one of Items 1 to 59, or a pharmaceutically acceptable salt thereof. [Section 62] The compound according to item 1 or a pharmaceutically acceptable salt thereof, selected from the following compounds: N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 1); N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 2), 2-[(1'S)-5'-{1-[2-(azetidin-1-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 3), N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclobutyl]acetamide (Example 4), N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1'S)-5'-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]acetamide (Example 5), N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-{(1′S)-5′-[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]-2,3′,5-trioxo-2′,3′-dihydrospiro[imidazolidine-4,1′-inden]-1-yl}acetamide (Example 6), N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide (Example 7), N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)acetamide (Example 8), N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-4-(trifluoromethyl)piperidin-4-yl]acetamide (Example 9), N-[(4-fluorophenyl)methyl]-2-(6-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-1,1,2',5'-tetraoxo-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl)-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 10), N-[(4-fluorophenyl)methyl]-2-{6-[1-(1-methylazetidine- 3-yl)-1H-pyrazol-4-yl]-1,1,2',5'-tetraoxo-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl}-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 11), 2-{(1'S)-5'-[1-(1-cyanocyclopropyl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Example 12), 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Example 13), N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Example 14), N-[(4-fluorophenyl)methyl]-2-[6-(1-methyl-1H-pyrazol-4-yl)-1,1,2',5'-tetraoxo-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Example 15), 2-{(1'S)-5'-[1-(1-cyclobutylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 16), N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(3-methoxyazetidin-1-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 17), 2-[(1'S)-5'-{1-[(2R)-2-(dimethylamino)propyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 18), N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 19), N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]-2-[(1'S)-2,3',5-trioxo-5'-{1-[1-(propyl-2-en-1-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide (Example 20), 2-[(1'S)-5'-{1-[1-(2,2-difluoroethyl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydro Drospiro[imidazolidine-4,1′-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 21), 2-[(1'S)-5'-{1-[1-(3,3-difluorocyclobutyl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 22), 2-[(1'S)-5'-{1-[3-(cyanomethyl)-1-methylazetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 23), 2-[(1'S)-5'-{1-[(2S)-2-(dimethylamino)propyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 24), 2-{(1'S)-5'-[1-(1-cyclopropylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 25), 2-[(1'S)-5'-{1-[(3-fluoro-1-methylazetidin-3-yl)methyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 26), N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide (Example 27), N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetan-3-yl)piperidin-4-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide (Example 28), 2-{(1'S)-5'-[1-(1-cyclobutylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide (Example 29), N-[(4-fluorophenyl)methyl]-2-(1,1,2',5'-tetraoxo-6-{1-[1-(propyl-2-yn-1-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl)-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 30), N-[(4-fluorophenyl)methyl]-2-(1,1,2',5'-tetraoxo-6-{1-[1-(propyl-2-en-1-yl)azetidin-3-yl]-1H-pyra {1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl)-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 31), 2-[(1'S)-3',3'-difluoro-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 32), 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 33), 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 34), 2-[(1'S)-3',3'-difluoro-2,5-dioxo-5'-(pyridin-3-yl)-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 35), 2-[(1'S)-3',3'-difluoro-2,5-dioxo-5'-(pyridin-4-yl)-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 36), 2-[(1'S)-3',3'-difluoro-2,5-dioxo-5'-(pyrimidin-5-yl)-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 37), 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 38), 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 39), 2-{(1'S)-3',3'-difluoro-2,5-dioxo-5'-[6-(pyrrolidin-1-yl)pyridin-3-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 40), 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 41), 2-{(1'S)-3',3'-difluoro-5'-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazole] {dazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 42), 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide (Example 43), 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-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 44), 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-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 45), 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 46), 2-[(1'S)-3',3'-difluoro-5'-{1-[(3-fluoro-1-methylazetidin-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 47), 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 48), 2-[(1'S)-5'-{1-[(2R)-2-(dimethylamino)propyl]-1H-pyrazol-4-yl}-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 49), 2-[(1'S)-3',3'-difluoro-5'-{1-[(3-fluoro-1-methylazetidin-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 50), 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide (Example 51), 2-{(1'S)-5'-[1-(azetidin-3-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imine {dazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 52), 2-{(1'S)-5'-[2-(dimethylamino)ethoxy]-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 53), 2-[(1'S)-3',3'-difluoro-5'-(3-methoxyazetidin-1-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 54), 2-[(1'S)-3',3'-difluoro-5'-(3-methoxypiperidin-1-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 55), N-[(4-fluorophenyl)methyl]-2-[(1'S)-3'-methylidene-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Example 56), N-[(4-fluorophenyl)methyl]-2-[(1'S)-3'-methylidene-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 57), N-[(4-fluorophenyl)methyl]-2-[(3′S)-6′-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2″,5″-dioxo-2′H-dispiro[cyclopropane-1,1′-indene-3′,4″-imidazolidine]-1″-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (Example 58), 2-[(1'S,3'R)-3'-Fluoro-3'-methyl-5'-(1-methyl-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 59). [Section 63] The compound according to item 1, selected from the following compounds, or a pharmaceutically acceptable salt thereof: 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 34), 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide (Example 43), 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-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 44) , 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-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 45), 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide (Example 46), 2-[(1'S)-3',3'-Difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide (Example 51). [Section 64] 64. A pharmaceutical comprising the compound according to any one of items 1 to 63 or a pharmaceutically acceptable salt thereof as an active ingredient. [Section 65] 64. A pharmaceutical composition comprising the compound according to any one of items 1 to 63 or a pharmaceutically acceptable salt thereof. [Section 66] Item 64. A therapeutic and / or preventive agent for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease, comprising the compound according to any one of Items 1 to 63 or a pharmaceutically acceptable salt thereof as an active ingredient. [Section 67] 64. A cancer treatment and / or prevention agent comprising the compound according to any one of items 1 to 63 or a pharmaceutically acceptable salt thereof as an active ingredient. [Section 68] Item 68. The therapeutic and / or preventive agent according to Item 66 or 67, wherein the cancer is at least one type of cancer selected from the group consisting of SMARC-deficient cancer, SS18-SSX fusion cancer, and ARID-deficient cancer. [Section 69] The cancer is selected from the group consisting of malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordotomy meningioma, neuroepithelial tumor, glioneuronal tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraskeletal myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, basaloid carcinoma of the paranasal sinus, esophageal cancer, papillary thyroid cancer, follicular thyroid cancer, gastrointestinal stromal tumor, pancreatic undifferentiated rhabdoid tumor, gastrointestinal rhabdoid tumor, renal medullary cancer, endometrial cancer, myoepithelioma-like tumor of the female vulva, colorectal cancer, mesothelioma, lung adenocarcinoma, large cell lung carcinoma, and pulmonary nerve tumor. Item 69. The therapeutic and / or prophylactic agent according to any one of Items 66 to 68, wherein the cancer is at least one type selected from the group consisting of endocrine tumors, gastroesophageal junction cancer, gastric cancer, bladder cancer, lung squamous cell carcinoma, pancreatic cancer, medulloblastoma, renal clear cell carcinoma, liver cancer, lung pleomorphic carcinoma, breast sarcoma, ovarian small cell carcinoma, primary gallbladder tumor, uterine sarcoma, ovarian granulosa tumor, adrenocortical carcinoma, small cell lung cancer, ovarian cancer, endometrial cancer, neuroblastoma, ovarian mucinous tumor, nasal and paranasal cancer, thoracic sarcoma, biliary tract cancer, neuroblastoma, melanoma, breast cancer, and Ewing's sarcoma. [Section 70] A method for treating or preventing cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease, comprising administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of the compound according to any one of items 1 to 63 or a pharmaceutically acceptable salt thereof. How to do this. [Section 71] Use of the compound or a pharmaceutically acceptable salt thereof according to any one of items 1 to 63 for the manufacture of a therapeutic or preventive agent for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease. [Section 72] Item 64. The compound or pharmaceutically acceptable salt thereof according to any one of Items 1 to 63, for use in the treatment or prevention of cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease. [Section 73] Item 64. The compound according to any one of Items 1 to 63, or a pharmaceutically acceptable salt thereof, for use in combination with a concomitant drug or a pharmaceutically acceptable salt thereof to treat cancer, wherein the concomitant drug is at least one or more selected from the group consisting of hormone therapy agents, chemotherapeutic agents, immunotherapy agents, and drugs that inhibit the action of cell growth factors and their receptors, or a pharmaceutically acceptable salt thereof. [Section 74] Item 64. A pharmaceutical composition according to any one of Items 1 to 63, comprising the compound according to any one of Items 1 to 63, or a pharmaceutically acceptable salt thereof, in combination with a concomitant drug, wherein the concomitant drug is at least one or more selected from the group consisting of hormone therapeutic agents, chemotherapeutic agents, immunotherapeutic agents, and drugs that inhibit the action of cell growth factors and their receptors. [Effects of the Invention]

[0013] The present disclosure provides CBP / P300 inhibitors, including tertiary amide derivatives substituted at a quaternary carbon and pharmaceutically acceptable salts thereof. The present disclosure provides drugs that inhibit the function of CBP / P300 and are applicable to a wide range of diseases and administration methods. The present disclosure also provides compounds represented by formula (1), which are tertiary amide derivatives substituted with a quaternary carbon, and drugs related thereto, that can be used as such drugs.

[0014] The compounds of the present disclosure exhibit excellent CBP / P300 inhibitory activity and are useful as therapeutic agents for diseases in which CBP / P300 is involved, and specifically are applicable to patients with cancer, non-alcoholic fatty liver disease (NAFLD), acute liver injury, heart disease, metabolic disease, etc. DETAILED DESCRIPTION OF THE INVENTION

[0015] The present disclosure will be described in more detail below. Throughout this specification, unless otherwise specified, singular expressions should be understood to include the plural concept. Therefore, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, it should be understood that terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In the case of conflict, the present specification (including definitions) will prevail.

[0016] The terms used in this specification are explained below.

[0017] In this specification, the number of substituents in a group defined as "optionally substituted" is not particularly limited as long as it is substitutable. When the number of substituents is specified and it is described as "substituted" with that number of substituents, it means that the group is substituted with that number of substituents. For example, "substituted with 2 to 5 substituents" means that the group is substituted with 2, 3, 4, or 5 substituents. Unless otherwise specified, the explanation of each group also applies when that group is a part or substituent of another group.

[0018] Examples of "halogen atom" include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom. A fluorine atom or a chlorine atom is preferred.

[0019] "C 1-6 "Alkyl" means a linear or branched saturated hydrocarbon group having 1 to 6 carbon atoms, and "C6 alkyl" means an alkyl group having 6 carbon atoms. The same applies to other numbers. 1-6 As the alkyl, preferably "C 1-4 alkyl" and more preferably "C 1-3 "C alkyl" is an example. 1-3Specific examples of "alkyl" include methyl, ethyl, propyl, 1-methylethyl, etc. 1-4 Specific examples of "alkyl" include the above-mentioned "C 1-3 In addition to the specific examples of "alkyl", butyl, 1,1-dimethylethyl, 1-methylpropyl, 2-methylpropyl, etc. are also included. 1-6 Specific examples of "alkyl" include the above-mentioned "C 1-4 In addition to the specific examples of "alkyl", pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 1-methylbutyl, 2-methylbutyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, hexyl, etc. are included.

[0020] "C 2-6 "Alkenyl" means a straight or branched chain unsaturated hydrocarbon group having 2 to 6 carbon atoms and containing 1 to 3 double bonds. 2-6 Alkenyl" is preferably "C 2-4 Alkenyl" is an example of "C 2-4 Specific examples of "alkenyl" include vinyl, propenyl, methylpropenyl, butenyl, etc. 2-6 Specific examples of "alkenyl" include the above-mentioned "C 2-4 In addition to the specific examples of "alkenyl", pentenyl, hexenyl, etc. are also included.

[0021] "C 2-6 The term "alkynyl" refers to a straight or branched unsaturated hydrocarbon group having 2 to 6 carbon atoms and containing one triple bond. 2-6 As "alkynyl", preferably "C 2-4 Alkynyl" is an example of "C 2-4 Specific examples of "alkynyl" include propynyl, methylpropynyl, butynyl, etc. 2-6 Specific examples of "alkynyl" include the above-mentioned "C 2-4 In addition to the specific examples of "alkynyl", methylbutynyl, pentynyl, hexynyl, etc. are included.

[0022] "C 1-6 "Alkoxy" means "C 1-6 "C alkyloxy" 1-6 The "C alkyl" portion is 1-6 "C" is synonymous with "alkyl." 1-6 The "alkoxy" is preferably "C 1-4 Alkoxy" is preferred, and "C 1-3 "Alkoxy" is one example. 1-3 Specific examples of "alkoxy" include methoxy, ethoxy, propoxy, 1-methylethoxy, etc. 1-4 Specific examples of "alkoxy" include the above-mentioned "C 1-3 In addition to the specific examples of "alkoxy", butoxy, 1,1-dimethylethoxy, 1-methylpropoxy, 2-methylpropoxy, etc. are also included. 1-6 Specific examples of "alkoxy" include the above-mentioned "C 1-4 In addition to the specific examples of "alkoxy", pentyloxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 1-methylbutoxy, 2-methylbutoxy, 4-methylpentyloxy, 3-methylpentyloxy, 2-methylpentyloxy, 1-methylpentyloxy, hexyloxy, and the like can be mentioned.

[0023] "C 1-6 "C" in "Alkylthio" 1-6 The "C alkyl" portion is 1-6 "C" is synonymous with "alkyl." 1-6 As the alkylthio, preferably "C 1-4 alkylthio", and more preferably "C 1-3 "C alkylthio" 1-3 Specific examples of "alkylthio" include methylthio, ethylthio, propylthio, 1-methylthio, and 1-methylthio. ethyl thio, etc. 1-4 Specific examples of "alkylthio" include the above-mentioned "C 1-3In addition to the specific examples of "alkylthio," butylthio, 1,1-dimethylethylthio, 1-methylpropylthio, 2-methylpropylthio, etc. are also included. 1-6 Specific examples of "alkylthio" include the above-mentioned "C 1-4 In addition to the specific examples of "alkylthio", pentylthio, 1,1-dimethylpropylthio, 1,2-dimethylpropylthio, 1-methylbutylthio, 2-methylbutylthio, 4-methylpentylthio, 3-methylpentylthio, 2-methylpentylthio, 1-methylpentylthio, hexylthio, and the like can be mentioned.

[0024] "C 1-6 "Alkylene" means a linear or branched divalent saturated hydrocarbon group having 1 to 6 carbon atoms. 1-6 As "alkylene", preferably "C 1-4 alkylene", and more preferably "C 1-3 "C alkylene" is an example. 1-3 Specific examples of "alkylene" include a methylene group, an ethylene group, and a propylene group. 1-4 Specific examples of "alkylene" include the above-mentioned "C 1-3 In addition to the specific examples of "alkylene," examples include a butylene group, a 1,1-dimethylethylene group, a 1,2-dimethylethylene group, a 1-methyltrimethylene group, and a 2-methyltrimethylene group. 1-6 Specific examples of "alkylene" include the above-mentioned "C 1-4 In addition to the examples given as specific examples of "alkylene," examples include a pentylene group, a 1,1-dimethyltrimethylene group, a 1,2-dimethyltrimethylene group, a 1-methylbutylene group, a 2-methylbutylene group, a 1-methylpentylene group, a 2-methylpentylene group, a 3-methylpentylene group, and a hexylene group.

[0025] "C 2-6 "Alkenylene" means a straight-chain or branched-chain divalent unsaturated hydrocarbon group having 2 to 6 carbon atoms and containing 1 to 3 double bonds. 2-6 Alkenylene" is preferably "C2-4 Alkenylene" is an example of "C 2-4 Specific examples of "alkenylene" include a vinylene group, a vinylidene group, a propenylene group, a methylpropenylene group, and a butenylene group. 2-6 Specific examples of "alkenyl" include the above-mentioned "C 2-4 In addition to the specific examples of "alkenyl", pentenylene group, hexenylene group, etc. are also included.

[0026] "C 3-10 The term "alicyclic group" refers to a cyclic saturated hydrocarbon group having 3 to 10 carbon atoms, and includes those having a partially unsaturated bond and those having a crosslinked structure. 3-10 As the "alicyclic group", preferably "C 3-7 Alicyclic groups are examples of "C 3-7 Specific examples of the "alicyclic group" include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, etc. 3-10 Specific examples of the "alicyclic group" include the above-mentioned "C 3-7 In addition to the specific examples of the "alicyclic group", cyclooctyl, cyclononyl, cyclodecyl, adamantyl, etc. are also included.

[0027] Also, "C 3-10 The "alicyclic group" includes the C 3-10 Bicyclic compounds in which an alicyclic group and an aromatic hydrocarbon ring are fused together are also included. Specific examples of such fused ring compounds include those having the structures shown below. [ka]

[0028] Specific examples of the crosslinked structure include the structures shown below. [ka]

[0029] "C 3-10"Cycloalkylene" means a cyclic divalent saturated hydrocarbon group having 3 to 10 carbon atoms, and includes those having a partially unsaturated bond and those having a crosslinked structure. 3-10 As "cycloalkylene", preferably "C 3-7 "Cycloalkylene" is an example. 3-7 Specific examples of "cycloalkylene" include cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, etc. 3-10 Specific examples of "cycloalkylene" include the above-mentioned "C 3-7 In addition to the specific examples of "cycloalkylene", cyclooctylene, cyclononylene, cyclodecylene, adamantylene, etc. are included.

[0030] Specific examples of the crosslinked structure include the structures shown below. [ka]

[0031] "C 3-10 "Cycloalkenylene" means a cyclic divalent unsaturated hydrocarbon group having 3 to 10 carbon atoms, including those with a bridged structure. 3-10 Specific examples of "cycloalkenylene" include cyclobutenylene, cyclopentenylene, cyclohexenylene, and the like.

[0032] The term "3- to 10-membered saturated carbocyclic ring" refers to a cyclic saturated hydrocarbon having 3 to 10 carbon atoms. A preferred example of the "3- to 10-membered saturated carbocyclic ring" is a "4- to 6-membered saturated carbocyclic ring." Specific examples of the "4- to 6-membered saturated carbocyclic ring" include a cyclobutane ring, a cyclopentane ring, and a cyclohexane ring. Specific examples of the "3- to 10-membered saturated carbocyclic ring" include the above-mentioned specific examples of the "4- to 6-membered saturated carbocyclic ring," as well as a cyclopropane ring, a cycloheptane ring, cyclooctane, cyclononane, and cyclodecane.

[0033] The term "4- to 10-membered non-aryl heterocyclic group" refers to a monovalent non-aryl heterocyclic group composed of 2 to 9 carbon atoms and 1 to 2 atoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, and includes those having a partially unsaturated bond and those having a bridged structure. The atoms constituting the ring may include those oxidized to -C(O)-, -S(O)-, and -SO2-. The "4- to 10-membered non-aryl heterocyclic group" is preferably a "4- to 6-membered non-aryl heterocyclic group." Specific examples of the "4- or 5-membered non-aryl heterocyclic group" include oxetanyl, azetidinyl, pyrrolidinyl, imidazolidinyl, oxazolidinyl, thiazolidinyl, oxoimidazolidinyl, dioxoimidazolidinyl, oxooxazolidinyl, dioxooxazolidinyl, dioxothiazolidinyl, tetrahydrofuranyl, piperidinyl, morpholinyl, thiomorpholinyl, dioxothiomorpholinyl, and tetrahydropyranyl. Examples of the "aryl heterocyclic group" include the specific examples of the "4- to 6-membered monocyclic non-aryl heterocyclic group" as well as azepanyl.

[0034] The "4- to 10-membered non-aryl heterocyclic group" also includes a bicyclic group in which the above-mentioned 4- to 10-membered non-aryl heterocyclic group and a 6-membered aromatic hydrocarbon ring or a 6-membered aromatic heterocyclic ring form a fused ring. Examples of the 6-membered aromatic hydrocarbon ring forming a fused ring include a benzene ring. Examples of the 6-membered aromatic heterocyclic ring forming a fused ring include pyridine, pyrimidine, and pyridazine. Specific examples of the bicyclic "4- to 10-membered non-aryl heterocyclic group" forming a fused ring include dihydroindolyl, dihydroisoindolyl, dihydropurinyl, dihydrothiazolopyrimidinyl, dihydrobenzodioxanyl, isoindolyl, indazolyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and tetrahydronaphthyridinyl.

[0035] The term "4- to 10-membered divalent non-aryl heterocyclic group" refers to a divalent non-aryl heterocyclic group composed of 2 to 9 carbon atoms and 1 to 2 atoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, and includes those having a partially unsaturated bond and those having a bridged structure. The atoms constituting the ring may include those oxidized to -C(O)-, -S(O)-, or -SO2-. The "4- to 10-membered divalent non-aryl heterocyclic group" is preferably a "4- to 6-membered divalent non-aryl heterocyclic group." Specific examples of the "4- to 6-membered divalent non-aryl heterocyclic group" include, for example, oxetanylene, azetidinylene, tetrahydrofurylene, pyrrolidinylene, imidazolidinylene, piperidinylene, morpholinylene, thiomorpholinylene, dioxothiomorpholinylene, hexamethyleneiminylene, oxazolidinylene, thiazolidinylene, oxoimidazolidinylene, dioxoimidazolidinylene, oxooxazolidinylene, dioxooxazolidinylene, dioxothiazolidinylene, tetrahydrofuranylene, tetrahydropyranylene, etc. Examples of the "4- to 10-membered divalent non-aryl heterocyclic group" include, in addition to the specific examples of the "4- to 6-membered divalent non-aryl heterocyclic group", azepanylene, etc.

[0036] Furthermore, the "4- to 10-membered divalent non-aryl heterocyclic group" also includes a bicyclic group in which the above-mentioned 4- to 10-membered divalent non-aryl heterocyclic group and a 6-membered aromatic hydrocarbon ring or a 6-membered aromatic heterocyclic ring form a fused ring. Examples of the 6-membered aromatic hydrocarbon ring forming a fused ring include a benzene ring. Examples of the 6-membered aromatic heterocyclic ring forming a fused ring include pyridine, pyrimidine, and pyridazine. Specific examples of the bicyclic "4- to 10-membered divalent non-aryl heterocyclic group" forming a fused ring include dihydroindolylene, dihydroisoindolylene, dihydropurinylene, dihydrothiazolopyrimidinylene, dihydrobenzodioxanylene, isoindolylene, indazolylene, tetrahydroquinolinylene, tetrahydroisoquinolinylene, and tetrahydronaphthyridinylene.

[0037] "C6-10 "Aryl" means an aromatic hydrocarbon ring group having 6 to 10 carbon atoms. 6-10 Specific examples of "aryl" include phenyl, 1-naphthyl, 2-naphthyl, etc. Preferably, phenyl is used.

[0038] Also, "C 6-10 "Aryl" includes the C 6-10 Aryl and C 4-6 Also included are bicyclic rings formed by condensing with an alicyclic group or a 5- to 6-membered non-aryl heterocycle. 6-10 Specific examples of "aryl" include groups shown below. [ka]

[0039] The "aromatic hydrocarbon ring" is defined as "C 6-10 The term "aryl" refers to the ring portion of an "aryl."

[0040] The term "5- to 10-membered heteroaryl" refers to a monocyclic 5- to 7-membered aromatic heterocyclic ring group or a bicyclic 8- to 10-membered aromatic heterocyclic ring group containing 1 to 4 atoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms. A "5- to 7-membered monocyclic heteroaryl" is preferred. Pyridyl, pyrimidinyl, quinolyl, or isoquinolyl is more preferred. Pyridyl is even more preferred. Specific examples of the "5- to 7-membered monocyclic heteroaryl" include pyridyl, pyridazinyl, isothiazolyl, pyrrolyl, furyl, thienyl, thiazolyl, imidazolyl, pyrimidinyl, thiadiazolyl, pyrazolyl, oxazolyl, isoxazolyl, pyrazinyl, triazinyl, triazolyl, oxadiazolyl, triazolyl, and tetrazolyl. Specific examples of the "5- to 12-membered heteroaryl" include, in addition to the specific examples of the "5- to 7-membered monocyclic heteroaryl", indolyl, indazolyl, chromenyl, quinolyl, isoquinolyl, benzofuranyl, benzothienyl, benzoxazolyl, benzothiazolyl, benzisoxazolyl, benzisothiazolyl, benzotriazolyl, benzimidazolyl, etc.

[0041] The term "aromatic heterocycle" refers to the ring moiety of the above "5- to 12-membered heteroaryl."

[0042] "3- to 10-membered cycloalkane" refers to a cyclic saturated hydrocarbon having 3 to 10 carbon atoms, and includes those having a partially unsaturated bond and those having a bridged structure, and a part of the ring may be fused with another ring. Specific examples of "3- to 10-membered cycloalkane" include cyclobutane, cyclopentane, cyclohexane, cycloheptane, etc.

[0043] The term "6- to 10-membered aromatic hydrocarbon ring" refers to a cyclic aromatic hydrocarbon having 6 to 10 carbon atoms, and a part of the ring may be condensed with another ring. Specific examples of the "6- to 10-membered aromatic hydrocarbon ring" include benzene and naphthalene.

[0044] The term "5- to 10-membered aromatic heterocycle" refers to a monocyclic 4- to 7-membered aromatic heterocycle or a bicyclic 8- to 12-membered aromatic heterocycle containing 1 to 4 atoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms, and a portion of the ring may be fused with another ring. Preferred examples include a "5- to 6-membered aromatic heterocycle," a "5-membered aromatic heterocycle," and a "6-membered aromatic heterocycle." Specific examples of "5- to 6-membered aromatic heterocycles" include furan, thiophene, oxazole, pyrazole, pyridine, pyrazine, pyrimidine, and pyridazine. Specific examples of "5-membered aromatic heterocycles" include pyrazole, furan, thiophene, and oxazole. Specific examples of "6-membered aromatic heterocycles" include pyridine, pyrazine, pyrimidine, and pyridazine.

[0045] The term "6- to 10-membered divalent aromatic hydrocarbon ring group" refers to a monocyclic or bicyclic divalent aromatic hydrocarbon ring group having 6 to 10 carbon atoms. As the "6- to 10-membered divalent aromatic hydrocarbon ring group", a "6-membered divalent aromatic hydrocarbon ring group" is preferably used. Specific examples of the "6- to 10-membered divalent aromatic hydrocarbon ring group" and the "6-membered divalent aromatic hydrocarbon ring group" include, for example, An example is divalent benzene.

[0046] The term "5- to 10-membered divalent aromatic heterocyclic group" refers to a monocyclic divalent 5- to 7-membered aromatic heterocyclic group or a bicyclic divalent 8- to 10-membered aromatic heterocyclic group containing 1 to 4 atoms independently selected from the group consisting of nitrogen, oxygen, and sulfur atoms. A "5- or 6-membered divalent aromatic heterocyclic group" is preferred, and a "5-membered divalent aromatic heterocyclic group" is more preferred. Specific examples of the "5-membered divalent aromatic heterocyclic group" include divalent pyrazole, divalent furan, divalent thiophene, and divalent oxazole. Examples of the "5- to 10-membered divalent aromatic heterocyclic group" and the "5- to 6-membered divalent aromatic heterocyclic group" include, in addition to the specific examples of the "5-membered divalent aromatic heterocyclic group," divalent pyridine, divalent pyrimidine, divalent pyrazine, and divalent pyridazine.

[0047] "Cancer" refers to malignant tumors, and includes carcinoma, sarcoma, and hematological malignancies. Specific examples of "cancer" include acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myeloid leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic, and promyelocytic), acute T-cell leukemia, basal cell carcinoma, gallbladder and bile duct 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, chronic myeloid leukemia, colorectal cancer, cystadenocarcinoma, diffuse large B-cell lymphoma, proliferative dysfunction (dysplasia and metaplasia), embryonic Carcinoma, endometrial cancer, epithelial sarcoma, ependymoma, epithelial carcinoma, erythroleukemia, esophageal cancer, estrogen receptor positive breast cancer, essential thrombocythemia, Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, glioblastoma, gliosarcoma, heavy chain disease, hemangioblastoma, liver cancer, hepatocellular carcinoma, hormone insensitive prostate cancer, leiomyosarcoma, leukemia, liposarcoma, lung cancer, lymphangiosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignant tumors and overgrowth of the bladder, breast, colon, lung, ovary, pancreas, prostate, skin and uterus Sexual disorders, lymphoid malignancies of T-cell or B-cell origin, leukemia, lymphoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, multiple myeloma, myeloid leukemia, myeloma, myxosarcoma, neuroblastoma, NUT midline carcinoma (NMC), non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinoma, papillary carcinoma, pinealoma, 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, Waldenstrom's macroglobulin These include hematoma, testicular tumor, uterine cancer, Wilms' tumor, malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordomatoid meningioma, neuroepithelial tumor, glioneuronal tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraskeletal myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, basaloid carcinoma of the paranasal sinus, esophageal adenocarcinoma, papillary thyroid cancer, follicular thyroid cancer, gastrointestinal stromal tumor, pancreatic undifferentiated rhabdoid tumor, gastrointestinal rhabdoid tumor, renal medullary cancer, endometrial cancer, myoepithelioma-like tumor of the female vulva, colorectal cancer, and mesothelioma.

[0048] In the present disclosure, "CBP" and "P300" are both histone acetyltransferases involved in chromatin regulation, and are paralogs. "CBP / P300" refers to "CBP" and "P300." Histone acetyltransferases are enzymes that transfer acetyl groups to lysine residues located primarily, but not exclusively, on the amino-terminal tails of histone proteins. CBP and P300 primarily, but not exclusively, acetylate histones H2A, H2B, H3, and H4. In particular, for histone H3, they acetylate primarily, but not exclusively, lysine 18, lysine 27, lysine 56, and lysine 122 (H3K18, H3K27, H3K56, and H3K122, respectively). In particular, acetylation of histone H3K27 is known as a marker of open chromatin and plays an important role in regulating gene expression (J Hum Genet. 2013 Jul; 58(7): 439-45). Acetylation of histone H3K27 is also known as a substrate of p53 (Cell. 1997 Aug; 90(4): 595-60). 6), MyoD (J Biol Chem. 2000 Nov; 275(44):34359-34364), STAT3 (Science. 2005 Jan; 307(5707):269-273), and androgen receptor (J Biol Chem. 2000 Jul; 275(27):20853-20860). As used herein, the terms "CBP" and "P300" generally refer to proteins, but may also refer to nucleic acids encoding them or conceptual genes, depending on the context, and those skilled in the art will be able to appropriately understand this depending on the context.

[0049] Important functional domains of CBP and P300 include the HAT domain, bromodomain (BRD), and CH1 / CH2 / CH3 domain (cysteine-histidine HAT domains are primarily, but not exclusively, domains that transfer acetyl groups to lysine residues present on the amino-terminal tails of histone proteins. Bromodomains are protein domains that recognize N-acetylated lysine residues found primarily, but not exclusively, on the amino-terminal tails of histone proteins.

[0050] As used herein, the term "CBP," unless otherwise specified, refers to any native CBP from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats). The term encompasses unprocessed CBP and any form of CBP resulting from processing in cells. The term also encompasses naturally occurring variants of CBP, such as splice variants or allelic variants. Human CBP is registered under UniProt Accession Number: Q92793. Representative amino acid sequences of human CBP are set forth in UniProt Q92793-1 (SEQ ID NO: 1) or UniProt Q92793-2 (SEQ ID NO: 2).

[0051] As used herein, the term "P300," unless otherwise specified, refers to any native P300 from any vertebrate source, including mammals such as primates (e.g., humans) and rodents (e.g., mice and rats). The term encompasses unprocessed P300 and any form of P300 resulting from processing in cells. The term also encompasses naturally occurring variants of P300, such as splice variants or allelic variants. Human P300 is registered under UniProt Accession Number: Q09472. A representative amino acid sequence of human P300 is set forth in UniProt Accession Number Q09472-1 (SEQ ID NO: 3).

[0052] A "CBP / P300 inhibitor" is a substance that inactivates, reduces the activity, and / or reduces the expression of CBP and / or P300. "Reducing CBP / P300 expression" may be an inhibitor that acts at any stage, such as the pre-transcriptional level (e.g., genomic level), the transcriptional level, the post-transcriptional regulatory level, the translational level, or the post-translational modification level. Preferred "CBP / P300 inhibitors" are HAT inhibitors and BRD inhibitors, and more preferably HAT inhibitors.

[0053] The term "HAT inhibitor" refers to a compound that inhibits the histone acetyltransferase (HAT) activity of CBP and / or P300. Histone acetyltransferase activity can be detected, for example, by fluorescent detection of CoA-SH, which is generated as a by-product during the histone acetyltransferase reaction (e.g., Gao T. et al., Methods Mol Biol. 2013; 981: 229-38), radioisotope detection (e.g., Lau OD et al., J Biol Chem. 2000; 275(29): 21953-9), or by converting acetylated histone peptides into TR-F. Methods for detection using the RET method (e.g., PerkinElmer's LANCE Ultra product or AlphaLISA product), and methods for detection using NADH (e.g., Berndsen et al. Methods. 2005; 36(4): 321-31) can be used. Examples of HAT inhibitors include compounds disclosed in WO2016 / 044770, WO2016 / 044771, WO2016 / 044777, WO2018 / 235966, WO2019 / 111980, WO2019 / 049061, WO2019 / 161162, WO2019 / 161157, WO2019 / 201291, and WO2020 / 108500.

[0054] A "BRD inhibitor" is a compound that inhibits the function of the bromodomain (BRD) of CBP and / or P300. Bromodomain function can be detected, for example, by using the TR-FRET method to detect the binding between the bromodomain and an acetylated lysine residue (e.g., Acta Pharmacol Sin. 2020; 41(2):286-292). Examples of BRD inhibitors include compounds disclosed in WO2017 / 205538, WO2016 / 086200, WO2018 / 073586, WO2019 / 055877, WO2017 / 140728, WO2019 / 191667, and WO2019 / 195846.

[0055] Histone acetyltransferase (HAT) activity is an enzymatic activity that transfers an acetyl group to a lysine residue in a substrate protein, such as histone protein or p53.

[0056] Bromodomains are protein domains that recognize N-acetylated lysine residues, which are found, for example, on the amino-terminal tails of histone proteins.

[0057] In the compounds of the present disclosure represented by formula (1), (2), (3), (4), (5), (6), or (7), A, B, R 1 , R 2a , R 2b , R 3 , R 4 , R 5 , R 6a , R 6b , R 7a , R 7b , R 7c , R 7d , R 7e , R 7f , R 8 , R 9a , R 9b Preferred examples of a, b, ring Q and Z are as follows, but the technical scope of the present disclosure is not limited to the range of compounds listed below.

[0058] A preferred embodiment of A is CR 6a R 6b , C=O, C=CH2, or S(=O)2.

[0059] A more preferred embodiment of A is CR 6a R 6b or C=O.

[0060] A more preferred embodiment of A is CR 6a R 6b Examples include:

[0061] An even more preferred embodiment of A is CF2.

[0062] A preferred embodiment of B is represented by the following formula (B-1). [ka] [wherein * represents the bonding position to the nitrogen atom of the hydantoin ring] More preferred embodiments of B include the following formula (B-2), (B-3) or (B-4). [ka] [wherein * represents the bonding position to the nitrogen atom of the hydantoin ring]

[0063] R 1 A preferred embodiment of the formula is C 1-6 Alkyl, or C 3-10 Examples include alicyclic groups (the alkyl or alicyclic groups may be substituted with 1 to 3 identical or different halogen atoms).

[0064] R 1 A more preferred embodiment of the above is C 1-6 Alkyl, or C 3-10 Examples include alicyclic groups (the alkyl or alicyclic group may be substituted with 1 to 3 fluorine atoms).

[0065] R 1 In a more preferred embodiment, C optionally substituted with 1 to 3 fluorines is 1-3 Examples of alkyl include: R 1 An even more preferred embodiment of is CF3.

[0066] R 2a and R 2b In a preferred embodiment, C may be independently substituted with 1 to 3 identical or different halogen atoms. 1-6 Examples of alkyl include: R 2a and R 2b Another preferred embodiment of R 2a and R 2b together with the carbon atom to which it is attached, C 3-6 Examples include forming a cycloalkylene or a 4- to 6-membered divalent non-aryl heterocyclic group (the cycloalkylene or divalent non-aryl heterocyclic group may be substituted with 1 to 3 identical or different halogen atoms).

[0067] R 2a and R 2b Another preferred embodiment of R 2a and R 2b together with the carbon atom to which it is attached, C 3-6 Cycloalkylene or a 4- to 6-membered divalent non-aryl heterocyclic group (the cycloalkylene or divalent non-aryl heterocyclic group is substituted with 1 to 3 fluorine atoms). Examples include the case where a substituted or unsubstituted alkyl group is formed.

[0068] R 3 A preferred embodiment of the formula is C 6-10 Aryl, 5-10 membered heteroaryl, C 3-10 an alicyclic group, or a 4- to 10-membered non-aryl heterocyclic group (the aryl, heteroaryl, alicyclic group, or non-aryl heterocyclic group is not substituted with a halogen atom or C 1-6 alkyl).

[0069] R 3 A more preferred embodiment of the above is C 6-10 Aryl (the aryl is a halogen atom and C 1-6 alkyl).

[0070] R 3 A more preferred embodiment of the formula is C 6-10 Aryl (the aryl is a fluorine atom and C 1-6 alkyl).

[0071] R 3 An even more preferred embodiment of is 4-fluorophenyl.

[0072] R 4 Preferred embodiments of the formula include a single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and the like. The alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of:

[0073] R 4 More preferred embodiments of the group include a single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and the like. The alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of:

[0074] R 4 A more preferred embodiment of is a 4- to 6-membered divalent non-aryl heterocyclic group.

[0075] R 4 An even more preferred embodiment of is azetidinylene.

[0076] R 4 In another more preferred embodiment, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl).

[0077] R 5 Preferred embodiments of the group include a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, and -NR 7b R 7c , -SO2R 7d or -CONR 7e R 7f , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkenyl (the alkenyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkynyl (the alkynyl is a halogen atom, C 1-6Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 6-10 Aryl (the aryl is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and 5- to 10-membered heteroaryl (the heteroaryl may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 or a 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and the like. The alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of:

[0078] R 5 More preferred embodiments of the group include a hydrogen atom, cyano, -NR 7b R 7c , -SO2R 7d or -CONR 7e R 7f , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 or a 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and the like. The alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of:

[0079] R 5 More preferred embodiments of the group include cyano, C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 or a 4- to 6-membered non-aryl heterocyclic group (the non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and the like. The alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of:

[0080] R 5 Even more preferred embodiments of include cyano, methyl group, or oxetane.

[0081] R 6a and R 6b In a preferred embodiment, each independently represents a fluorine atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl).

[0082] R 6a and R 6bMore preferred embodiments of the above are each independently a fluorine atom or a methyl group.

[0083] R 6a and R 6b More preferred embodiments of the above are each independently a fluorine atom.

[0084] R 7a , R 7b , R 7c , R 7d , R 7e and R 7f In a preferred embodiment, each independently represents a hydrogen atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl).

[0085] R 7a , R 7b , R 7c , R 7d , R 7e and R 7f In a more preferred embodiment, Each of these independently represents a hydrogen atom or a methyl group.

[0086] R 8 In a preferred embodiment, it is a hydrogen atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl).

[0087] R 8 A more preferred embodiment of the above is C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl).

[0088] R 8 A more preferred embodiment of is a methyl group.

[0089] R 9a and R 9b In a preferred embodiment, each independently represents a hydrogen atom, a halogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl).

[0090] R 9a and R 9b More preferred embodiments of the above are each independently a halogen atom.

[0091] R 9a and R 9b A more preferred embodiment of is a fluorine atom.

[0092] R 10 A preferred embodiment of the formula is C 1-6 Examples of alkyl include:

[0093] R 11 and R 12 In a preferred embodiment, each independently represents a hydrogen atom or C 1-6 Examples of alkyl include:

[0094] R 11 and R 12 In another preferred embodiment, R 11 and R 12 Both are C 1-6 When they are alkyl, they may be combined with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle.

[0095] A preferred embodiment of ring Q is a 6- to 10-membered aromatic hydrocarbon ring (the aromatic hydrocarbon ring is substituted with a halogen atom and C 1-6 alkyl).

[0096] A more preferred embodiment of ring Q is benzene.

[0097] Preferred embodiments of Z include —O—, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and a 5- to 10-membered divalent aromatic heterocyclic group (which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and --NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of A more preferred embodiment of Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 or a 5- to 10-membered divalent aromatic heterocyclic group (which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 mosquito and the alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of: A more preferred embodiment of Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and the like. The alkyl group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of:

[0098] An even more preferred embodiment of Z is pyrazole.

[0099] Preferred embodiments of a include 0, 1, and 2.

[0100] More preferred embodiments of a include 1 and 2.

[0101] A more preferred embodiment of a is 1.

[0102] Preferred embodiments of b include 1 and 2.

[0103] A more preferred embodiment of b is 1.

[0104] One embodiment of the compound represented by formula (1) is the following (A). (A) A is CF2, C(F)CH3, or C=O; B is the following formula (B-1): [ka] [wherein * represents the bonding position to the nitrogen atom of the hydantoin ring], Ring Q is a 6- to 10-membered aromatic hydrocarbon ring (the aromatic hydrocarbon ring is not substituted with a halogen atom or C 1-6 alkyl), Z is -O-, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and a 5- to 10-membered divalent aromatic heterocyclic group (which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and --NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 1 C optionally substituted with 1 to 3 fluorines 1-3 is alkyl, R 2a and R 2b together with the carbon atoms to which they are attached, C 3-6 forming a cycloalkylene or a 4- to 6-membered divalent non-aryl heterocyclic group (the cycloalkylene or divalent non-aryl heterocyclic group may be substituted with 1 to 3 fluorine atoms); R 3 But C 6-10 Aryl (the aryl is a halogen atom and C 1-6 alkyl), R 4 is a single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 is a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, -NR 7b R 7c , -SO2R 7d or -CONR 7e R 7f , C1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkenyl (the alkenyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkynyl (the alkynyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 6-10 Aryl (the aryl is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and 5- to 10-membered heteroaryl (the heteroaryl may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 or a 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7b , R 7c , R 7d , R 7e and R 7f are each independently a hydrogen atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0105] One embodiment of the compound represented by formula (1) is the following (B). (B) A is CF2 or C=O, B is represented by the following formula (B-2), (B-3), or (B-4): [ka] [wherein * represents the bonding position to the nitrogen atom of the hydantoin ring, a is 0, 1, or 2; b is 1 or 2, R 8 is a hydrogen atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6alkyl), R 9a and R 9b are each independently a hydrogen atom, a halogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), and Ring Q is a 6- to 10-membered aromatic hydrocarbon ring (the aromatic hydrocarbon ring is not substituted with a halogen atom or C 1-6 alkyl), Z is -O-, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and a 5- to 10-membered divalent aromatic heterocyclic group (which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and --NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 1 is CF3, R 3 is 4-fluorophenyl, R 4 is a single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 is a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, -NR 7b R 7c , -SO2R 7d or -CONR 7e R 7f , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkenyl (the alkenyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkynyl (the alkynyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 A group consisting of may be substituted with 1 to 3 identical or different substituents selected from 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 6-10Aryl (the aryl is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and 5- to 10-membered heteroaryl (the heteroaryl may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 or a 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group may be substituted with 1 to 3 identical or different substituents selected from the group consisting of halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7b , R 7c , R 7d , R 7e and R 7f are each independently a hydrogen atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0106] One embodiment of the compound represented by formula (2) is the following (C). A is CF2 or C=O, Z, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 but, hydrogen atoms, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7b , R 7c However, each independently, a hydrogen atom, or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0107] One embodiment of the compound represented by formula (2) is the following (D). A is CF2, Z is a 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 but, hydrogen atoms, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 1-6 Alkoxy (the alkoxy is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 7b , R 7c are each independently a hydrogen atom or C 1-6 Alkyl (the alkyl is a halogen atom and C 1-6 alkyl), R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0108] One embodiment of the compound represented by formula (3) is the following (E). R 4 is a 4- to 6-membered divalent non-aryl heterocyclic group, R 5 but, C 1-3 alkyl, or 4- to 6-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not substituted with a halogen atom or C 1-6 and (optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of alkyl, The compound or a pharmaceutically acceptable salt thereof.

[0109] One embodiment of the compound represented by formula (3) is the following (F). R 4 is azetidinylene, R 5 but, methyl, or oxetanyl, The compound or a pharmaceutically acceptable salt thereof.

[0110] One embodiment of the compound represented by formula (4) is the following (G). A is CF2 or C=O, Z, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is 1-6 Alkyl and -NR 11 R 12and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), R 5 but, hydrogen atoms, Cyano, C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 8 But C 1-6 is alkyl, R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0111] One embodiment of the compound represented by formula (4) is the following (G). A is CF2, Z is a 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 A group consisting of alkyl and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: C 3-10 Cycloalkylene (the cycloalkylene is a halogen atom and C 1-6 alkyl), R 5 but, hydrogen atoms, Cyano, C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 8 is a methyl group, R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0112] One embodiment of the compound represented by formula (5) is the following (H). R 4 but, a single bond, or C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), R 5 but, C 1-6 alkyl, or It is cyano, The compound or a pharmaceutically acceptable salt thereof.

[0113] One embodiment of the compound represented by formula (5) is the following (I): R 4 but, is a single bond, R 5 but, a methyl group, or It is cyano, The compound or a pharmaceutically acceptable salt thereof.

[0114] One embodiment of the compound represented by formula (5) is the following (J). R 4 but, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), R 5 but, a methyl group, or It is cyano, The compound or a pharmaceutically acceptable salt thereof.

[0115] One embodiment of the compound represented by formula (6) is (K) below. A is CF2 or C=O, Z, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 but, hydrogen atoms, Cyano, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 9a and R 9b is a halogen atom, R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0116] One embodiment of the compound represented by formula (6) is the following (L). A is CF2, Z, 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 4 but, single bond, C 1-6 Alkylene (the alkylene is a halogen atom and C 1-6 alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 5 but, hydrogen atoms, Cyano, -NR 7b R 7c , C 1-6 Alkyl (the alkyl is a halogen atom, C 1-6 Alkyl, hydroxyl and -NR 11 R 12 may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C 3-10 Alicyclic group (the alicyclic group is a halogen atom, C 1-6 Alkyl and -NR 11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4-10 membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C 1-6 Alkyl and -NR11 R 12 and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R 9a and R 9b is a fluorine atom, R 11 and R 12 are each independently a hydrogen atom or C 1-6 is alkyl, R 11 or R 12 If there are multiple 11 or R 12 may be the same or different, and R 11 and R 12 Both are C 1-6 When they are alkyl, they may be taken together with the nitrogen atom to which they are bonded to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. The compound or a pharmaceutically acceptable salt thereof.

[0117] One embodiment of the compound represented by formula (7) is the following (M). R 4 but, a 4- to 6-membered divalent non-aryl heterocyclic group, R 5 but, C 1-3 alkyl, or a 4- to 6-membered non-aryl heterocyclic group; The compound or a pharmaceutically acceptable salt thereof.

[0118] One embodiment of the compound represented by formula (7) is the following (N). R 4 but, is azetidinylene, R 5 but, is methyl, The compound or a pharmaceutically acceptable salt thereof.

[0119] One embodiment of the compound represented by formula (7) is the following (O). R 4 but, is azetidinylene, R 5 but, oxetanyl, The compound or a pharmaceutically acceptable salt thereof.

[0120] The compound of the present disclosure may be administered orally, parenterally, or rectally, with the daily dosage varying depending on the type of compound, the administration method, the patient's symptoms, age, and other factors. For example, oral administration typically involves administering approximately 0.01 to 1,000 mg, more preferably approximately 0.1 to 500 mg, per kg of body weight to a human or mammal, in one or several divided doses. Parenteral administration, such as intravenous injection, typically involves administering approximately 0.01 to 300 mg, more preferably approximately 1 to 100 mg, per kg of body weight to a human or mammal. Examples of administration schedules include a single dose, once daily for three consecutive days, or twice daily for one week. Furthermore, each of the above-described administration methods can be repeated at intervals of approximately 1 to approximately 60 days.

[0121] The compounds of the present disclosure can be administered parenterally or orally, either directly or after formulation using an appropriate dosage form. Examples of dosage forms include, but are not limited to, tablets, capsules, powders, granules, liquids, suspensions, injections, patches, and poultices. The formulations are prepared by known methods using pharmaceutically acceptable additives. Depending on the purpose, additives that can be used include excipients, disintegrants, binders, flow agents, lubricants, coating agents, solubilizers, solubilizers, thickeners, dispersants, stabilizers, sweeteners, and flavors. Specific examples of additives include lactose, mannitol, crystalline cellulose, low-substituted hydroxypropyl cellulose, corn starch, partially pregelatinized starch, carmellose calcium, croscarmellose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinyl alcohol, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, propylene glycol, titanium oxide, and talc.

[0122] Examples of methods for producing the compounds of the present disclosure represented by formulas (1) to (7) are described below, but the methods for producing the compounds of the present disclosure are not limited to these. The compounds used in the following production methods may form salts as long as they do not interfere with the reaction.

[0123] The compounds of the present disclosure can be produced using known compounds as starting materials by, for example, the following production methods A, B, C, and D, or methods similar thereto, or by appropriately combining synthesis methods known to those skilled in the art.

[0124] Manufacturing method A Among the compounds represented by formula (1), the compound (1-11) in which A is CF2 and Q is a benzene ring can be produced, for example, by the following production method. [ka] [In the formula, R 1 , R 2a , R 2b , R 4 , R5 and Z have the same meanings as in [Item 1] above.]

[0125] Step 1-1: Production process of compound (1-3) Compound (1-3) can be prepared by reacting compound (1-1) with compound (1-2) in an inert solvent with a reducing agent It is prepared by reacting in the presence of

[0126] Specific examples of the reducing agent include sodium borohydride, sodium triacetoxyborohydride, sodium cyanoborohydride, and the like.

[0127] Specific 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-pyrrolidinone.

[0128] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 0° C. to 25° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0129] Step 1-2: Preparation of Compound (1-5) Compound (1-5) is produced by an amidation reaction using compound (1-3) and compound (1-4) in an inert solvent in the presence of a base.

[0130] Specific examples of the base include inorganic bases such as potassium hydroxide, sodium hydroxide, and sodium hydride; and metal alkoxides such as sodium methoxide and potassium tert-butoxide.

[0131] Specific 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-pyrrolidinone, and N,N-dimethylpropylene urea.

[0132] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 25° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0133] Step 1-3: Preparation of Compound (1-6) Compound (1-6) can be prepared by deprotecting the benzyl group of compound (1-5) by, for example, catalytic reduction using a metal catalyst such as palladium / carbon or palladium hydroxide / carbon under a hydrogen atmosphere.

[0134] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 100° C., preferably 0° C. to 25° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0135] Step 1-4: Preparation of Compound (1-8) Compound (1-8) can be produced by reacting commercially available compound (1-7) with 1,2-ethanedithiol in an inert solvent in the presence of an acid.

[0136] Specific examples of the acid include boron trifluoride diethyl ether complex, p-toluenesulfonic acid, perchloric acid, and aluminum chloride.

[0137] Specific examples of the inert solvent include halogenated hydrocarbons such as chloroform and dichloromethane; aromatic hydrocarbons such as toluene; diethyl ether and tetrahydrofuran (TH F) ether solvents such as 1,4-dioxane; and aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidinone, and N,N-dimethylpropylene urea.

[0138] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 0° C. to 25° C. The reaction time is usually 30 minutes to 72 hours, preferably 30 minutes to 24 hours.

[0139] Step 1-5: Preparation of Compound (1-9) Compound (1-9) can be produced by reacting compound (1-8) with a brominating agent and a fluorinating agent in an inert solvent.

[0140] Specific 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-pyrrolidinone, and N,N-dimethylpropylene urea.

[0141] Specific examples of the brominating agent include N-bromosuccinimide and 1,3-dibromo-5,5-dimethylhydantoin.

[0142] Specific examples of the fluorinating agent include hydrogen fluoride pyridine, potassium fluoride, cesium fluoride, and (diethylamino)sulfur trifluoride.

[0143] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 25° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0144] Step 1-6: Preparation of Compound (1-10) Compound (1-10) is produced by Mitsunobu reaction using compound (1-6) and compound (1-9) in the presence of a Mitsunobu reagent in an inert solvent.

[0145] Specific examples of the inert solvent include aromatic hydrocarbons such as toluene; and ether solvents such as diethyl ether, tetrahydrofuran (THF), 1,4-dioxane, and the like.

[0146] Examples of Mitsunobu reagents include diethyl azodicarboxylate (DEAD), isopropyl azodicarboxylate (DIAD), N,N,N',N'-tetramethylazodicarboxamide, triphenylphosphine, tributylphosphine, and the like, and cyanomethylenetrimethylphosphorane (Tsunoda reagent) can also be used.

[0147] The reaction temperature is not particularly limited, but is usually selected in the range of 0° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0148] Step 1-7: Preparation of Compound (1-11) Compound (1-11) can be produced by subjecting compound (1-10) to a palladium-catalyzed cross-coupling reaction using various coupling reagents in an inert solvent.

[0149] Specific examples of the inert solvent include aromatic hydrocarbons such as toluene; ether solvents such as diethyl ether, tetrahydrofuran (THF), and 1,4-dioxane; acetonite; Examples of suitable solvents include aprotic polar solvents such as methyl ether, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidinone, and N,N-dimethylpropylene urea.

[0150] Specific examples of palladium reagents include tetrakis(triphenylphosphine)palladium(0), bis(dibenzylideneacetone)palladium(0), tris(dibenzylideneacetone)dipalladium(0), bis(tri-tert-butylphosphine)palladium(0), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride.

[0151] Specific examples of the base include inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, and sodium hydroxide.

[0152] Specific examples of the coupling reagent include Z-bonded boronic acid, Z-bonded boronic acid pinacol ester, and the like.

[0153] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 25° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours. Manufacturing method B Among the compounds represented by formula (1), the compound (1-11) in which A is CF2 and Q is a benzene ring can also be produced by the following production method. [ka] [In the formula, R 1 , R 2a , R 2b , R 4 , R 5 and Z are as defined in [Item 1] above. W represents a halogen atom.]

[0154] Step 2-1: Production process of compound (2-1) Compound (2-1) can be obtained by reacting compound (1-3) with an amidating agent in an inert solvent. Manufactured by

[0155] Specific examples of the amidating agent include chloroacetyl chloride, bromoacetyl chloride, and chloroacetic anhydride.

[0156] Specific 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; aprotic polar solvents such as acetonitrile, acetone, methyl ethyl ketone, N,N-dimethylformamide, N-methyl-2-pyrrolidinone and N,N-dimethylpropylene urea; and pyridine.

[0157] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 25° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0158] Step 2-2: Preparation of Compound (1-10) Compound (1-10) is produced by alkylation reaction of compound (2-1) with compound (1-9) in the presence of a base in an inert solvent.

[0159] Specific 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-pyrrolidinone, and N,N-dimethylpropylene urea.

[0160] Specific examples of the base include inorganic bases such as potassium carbonate and cesium carbonate; and metal alkoxides such as sodium methoxide and potassium tert-butoxide.

[0161] The reaction temperature is not particularly limited, but is usually selected in the range of 0° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0162] Manufacturing method C Among the compounds represented by formula (1), the compound (1-11) in which A is CF2 and Q is a benzene ring can also be produced by the following production method. [ka] [In the formula, R 1 , R 2a , R 2b , R 4 , R 5 and Z have the same meanings as in [Item 1] above.]

[0163] Step 3-1: Production process of compound (3-1) Compound (3-1) can be produced by subjecting compound (1-9) to a palladium-catalyzed cross-coupling reaction using various coupling reagents in an inert solvent.

[0164] Specific 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-pyrrolidinone, and N,N-dimethylpropylene urea.

[0165] Specific examples of palladium reagents include tetrakis(triphenylphosphine)palladium(0), bis(dibenzylideneacetone)palladium(0), tris(dibenzylideneacetone)dipalladium(0), bis(tri-tert-butylphosphine)palladium(0), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride.

[0166] Specific examples of the base include inorganic bases such as potassium carbonate, sodium carbonate, cesium carbonate, potassium phosphate, potassium hydroxide, and sodium hydroxide.

[0167] Specific examples of the coupling reagent include Z-bonded boronic acid, Z-bonded boronic acid pinacol ester, and the like.

[0168] The reaction temperature is not particularly limited, but is usually selected from the range of 0° C. to 150° C., preferably 25° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0169] Step 3-2: Preparation of Compound (1-11) Compound (1-11) is produced by Mitsunobu reaction using compound (3-1) and compound (1-6) in the presence of a Mitsunobu reagent in an inert solvent.

[0170] Specific examples of the inert solvent include aromatic hydrocarbons such as toluene; and ether solvents such as diethyl ether, tetrahydrofuran (THF), 1,4-dioxane, and the like.

[0171] Examples of Mitsunobu reagents include diethyl azodicarboxylate (DEAD), isopropyl azodicarboxylate (DIAD), N,N,N',N'-tetramethylazodicarboxamide, triphenylphosphine, tributylphosphine, and the like, and cyanomethylenetrimethylphosphorane (Tsunoda reagent) can also be used.

[0172] The reaction temperature is not particularly limited, but is usually selected in the range of 0° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0173] Manufacturing method D Among the compounds represented by formula (1), the compound (1-11) in which A is CF2 and Q is a benzene ring can also be produced by the following production method. [ka] [In the formula, R 1 , R 2a , R2b , R 4 , R 5 and Z are as defined in [Item 1] above. W represents a halogen atom.]

[0174] Step 4-1: Preparation of Compound (1-11) Compound (1-11) is produced by alkylation reaction using compound (3-1) and compound (2-1) in the presence of a base in an inert solvent.

[0175] Specific 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-pyrrolidinone, and N,N-dimethylpropylene urea.

[0176] Specific examples of the base include inorganic bases such as potassium carbonate and cesium carbonate; and metal alkoxides such as sodium methoxide and potassium tert-butoxide.

[0177] The reaction temperature is not particularly limited, but is usually selected in the range of 0° C. to 100° C. The reaction time is usually 1 hour to 72 hours, preferably 1 hour to 24 hours.

[0178] In the above-described production methods, starting materials or intermediates for which production methods are not described are commercially available or can be synthesized from commercially available compounds by methods known to those skilled in the art or methods similar thereto.

[0179] In each reaction of the production method described above, even when the use of a protecting group is not specifically specified, a protecting group can be used as needed. For example, when any functional group other than the reactive site changes under the reaction conditions described, or when the method described is inappropriate to carry out without a protecting group, the target compound can be obtained by protecting the functional group other than the reactive site as needed and deprotecting it after the reaction or after a series of reactions.

[0180] Examples of the protecting group that can be used include those described in Protective Groups in Organic Synthesis (Theodora W. Greene, Peter G.M. Wuts, John Wiley & Sons, Inc., 1999). Specific examples of the amino protecting group include benzyloxycarbonyl, tert-butoxycarbonyl, acetyl, benzyl, etc. Specific examples of the hydroxyl protecting group include trialkylsilyl such as trimethylsilyl and tert-butyldimethylsilyl, acetyl, benzyl, etc.

[0181] The introduction and removal of the protecting group can be carried out by a method commonly used in organic synthetic chemistry (for example, the above-mentioned Protective Group Groups in Organic Synthesis) or a method analogous thereto.

[0182] In this specification, protecting groups, condensing agents, etc. may be represented by abbreviations according to IUPAC-IUB (International Union of Biochemical Nomenclature Commission), which are commonly used in this technical field. Note that the names of compounds used in this specification do not necessarily conform to the IUPAC nomenclature.

[0183] The intermediates or target compounds in the above-described production methods can be converted into other compounds included in the present disclosure by appropriately converting their functional groups (for example, by protecting or deprotecting the functional groups as necessary, and then performing various conversions using amino, hydroxyl, carbonyl, halogen, etc. as a stepping stone). The conversion of functional groups can be performed by a commonly used method (see, for example, Comprehensive Organic Transformations, RC Larock, John Wiley & Sons Inc. (1999)).

[0184] The intermediates and target compounds in the production methods described above can be isolated and purified by purification methods commonly used in organic synthetic chemistry (e.g., neutralization, filtration, extraction, washing, drying, concentration, recrystallization, various types of chromatography, etc.). In addition, the intermediates can also be used in the next reaction without any particular purification.

[0185] Examples of the protecting group that can be used include those described in Protective Groups in Organic Synthesis (Theodora W. Greene, Peter G.M. Wuts, John Wiley & Sons, Inc., 1999). Specific examples of the amino protecting group include benzyloxycarbonyl, tert-butoxycarbonyl, acetyl, benzyl, etc. Specific examples of the hydroxyl protecting group include trialkylsilyl such as trimethylsilyl and tert-butyldimethylsilyl, acetyl, benzyl, etc.

[0186] The introduction and removal of the protecting group can be carried out by a method commonly used in organic synthetic chemistry (for example, the above-mentioned Protective Group Groups in Organic Synthesis) or a method analogous thereto.

[0187] In this specification, protecting groups, condensing agents, etc. may be represented by abbreviations according to IUPAC-IUB (International Union of Biochemical Nomenclature Commission), which are commonly used in this technical field. Note that the names of compounds used in this specification do not necessarily conform to the IUPAC nomenclature.

[0188] The intermediates or target compounds in the above-described production methods can be converted into other compounds included in the present disclosure by appropriately converting their functional groups (for example, by protecting or deprotecting the functional groups as necessary, and then performing various conversions using amino, hydroxyl, carbonyl, halogen, etc. as a stepping stone). The conversion of functional groups can be performed by a commonly used method (see, for example, Comprehensive Organic Transformations, RC Larock, John Wiley & Sons Inc. (1999)).

[0189] The intermediates and target compounds in the production methods described above can be isolated and purified by purification methods commonly used in organic synthetic chemistry (e.g., neutralization, filtration, extraction, washing, drying, concentration, recrystallization, various types of chromatography, etc.). In addition, the intermediates can also be used in the next reaction without any particular purification.

[0190] The term "pharmaceutically acceptable salt" includes acid addition salts and base addition salts. For example, acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, hydroiodide, nitrate, and phosphate, and salts of citrate, oxalate, phthalate, fumarate, maleate, succinate, malate, acetate, formate, propionate, benzoate, trifluoromethane, and the like. Examples of the base addition salt include inorganic base salts such as sodium salt, potassium salt, calcium salt, magnesium salt, barium salt, and aluminum salt, and organic base salts such as trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, tromethamine [tris(hydroxymethyl)methylamine], tert-butylamine, cyclohexylamine, dicyclohexylamine, and N,N-dibenzylethylamine. Furthermore, examples of the "pharmaceutically acceptable salt" include amino acid salts with basic or acidic amino acids such as arginine, lysine, ornithine, aspartic acid, and glutamic acid.

[0191] Suitable salts of starting materials and intermediates, as well as salts acceptable as pharmaceutical raw materials, are conventional non-toxic salts, including, for example, acid addition salts such as organic acid salts (e.g., acetate, trifluoroacetate, maleate, fumarate, citrate, tartrate, methanesulfonate, benzenesulfonate, formate, toluenesulfonate, etc.) and inorganic acid salts (e.g., hydrochloride, hydrobromide, hydroiodide, sulfate, nitrate, phosphate, etc.), salts with amino acids (e.g., arginine, aspartic acid, glutamic acid, etc.), metal salts such as alkali metal salts (e.g., sodium salt, potassium salt, etc.) and alkaline earth metal salts (e.g., calcium salt, magnesium salt, etc.), ammonium salts, organic base salts (e.g., trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, N,N'-dibenzylethylenediamine salt, etc.), and others that can be appropriately selected by those skilled in the art.

[0192] Compounds of the present disclosure may be isotopically enriched, 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 I, etc.), and these compounds are also included in the compounds of the present disclosure.

[0193] The present disclosure includes compounds represented by formulas (1) to (7) or pharmaceutically acceptable salts thereof. In addition, the compounds of the present disclosure may exist in the form of hydrates and / or solvates with various solvents (such as ethanolates), and these hydrates and / or solvates are also included in the compounds of the present disclosure.

[0194] Furthermore, the compounds of the present disclosure include all possible isomers such as optical isomers based on optically active centers, atropisomers based on axial or planar chirality resulting from restricted intramolecular rotation, other stereoisomers, tautomers, geometric isomers, and the like, as well as all types of crystalline forms, and mixtures thereof.

[0195] In particular, optical isomers and atropisomers can be obtained as racemates, or as optically active isomers when optically active starting materials or intermediates are used. Furthermore, if necessary, at an appropriate stage of the production method, the racemate of the corresponding starting material, intermediate, or final product can be physically or chemically resolved into its optical antipodes by known separation methods such as a method using an optically active column or fractional crystallization. Examples of such resolution methods include a diastereomeric method in which a racemate is reacted with an optically active resolving agent to synthesize two diastereomers, which are then separated by a method such as fractional crystallization, taking advantage of their different physical properties.

[0196] When it is desired to obtain a pharmaceutically acceptable salt of a compound of the present disclosure, if the compound represented by formulas (1) to (7) is obtained in the form of a pharmaceutically acceptable salt, it can be purified as is. Alternatively, if it is obtained in the free form, it can be dissolved or suspended in an appropriate organic solvent, and an acid or a base can be added to form a salt by a conventional method.

[0197] The compounds of the present disclosure can be used in combination with other drugs to enhance their effects. Specifically, the compounds of the present disclosure can be used in combination with drugs such as hormone therapy agents, chemotherapy agents, immunotherapy agents, or drugs that inhibit cell growth factors and their receptor activity. Hereinafter, drugs that can be used in combination with the compounds of the present disclosure will be abbreviated as "concomitant drugs."

[0198] The compounds of the present disclosure exhibit excellent anticancer effects even when used as single agents, but by further using them in combination with one or more of the above-mentioned concomitant drugs (multidrug combination), the effects can be further enhanced or the patient's QOL can be improved.

[0199] Examples of "hormonal therapeutic agents" include fosfestrol, diethylstilbestrol, chlorotrianisene, medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, cyproterone acetate, danazol, dienogest, asoprisnil, allylestrenol, gestrinone, nomegestol, tadenane, mepartricin, raloxifene, ormeloxifene, levormeloxifene, antiestrogens (e.g., tamoxifen citrate, toremifene citrate, etc.), birth control pills, mepitiostane, testololactone, aminoglutethimide, LH-RH derivatives (LH-RH agonists (e.g., goserelin acetate, buserelin, levothyroxine), levothyroxine, ... prorelin, etc.), LH-RH antagonists), droloxifene, epitiostanol, ethinyl estradiol sulfonate, aromatase inhibitors (e.g., fadrozole hydrochloride, anastrozole, letrozole, exemestane, vorozole, formestane, etc.), antiandrogens (e.g., flutamide, enzalutamide, apalutamide, bicalutamide, nilutamide, etc.), corticosteroids (e.g., dexamethasone, prednisolone, betamethasone, triamcinolone, etc.), androgen synthesis inhibitors (e.g., abiraterone, etc.), retinoids, and agents that slow the metabolism of retinoids (e.g., liarozole, etc.).

[0200] Examples of "chemotherapeutic agents" that can be used include alkylating agents, antimetabolites, anticancer antibiotics, plant-derived anticancer agents, molecular targeted therapeutic agents, immunomodulators, and other chemotherapeutic agents. Representative examples are listed below.

[0201] Examples of the "alkylating agent" include nitrogen mustard, nitrogen mustard-N-oxide hydrochloride, chlorambucil, cyclophosphamide, ifosfamide, thiotepa, carboquone, improsulfan tosylate, busulfan, nimustine hydrochloride, mitobronitol, melphalan, dacarbazine, ranimustine, estramustine sodium phosphate, triethylenemelamine, carmustine, lomustine, streptozotocin, Examples of drugs that can be used include benzodiazepine, pipobroman, etoglucide, carboplatin, cisplatin, miboplatin, nedaplatin, oxaliplatin, altretamine, ambamustine, dibrospidium hydrochloride, fotemustine, prednimustine, pumitepa, ribomustine, temozolomide, treosulfan, trofosfamide, zinostatin stimalamer, adozelesin, systostin, bizelesin, trabectedin, and DDS formulations thereof.

[0202] Examples of "antimetabolites" include mercaptopurine, 6-mercaptopurine riboside, thioinosine, methotrexate, pemetrexed, eocitabine, cytarabine, cytarabine ocfosfate, ancitabine hydrochloride, 5-FU drugs (e.g., fluorouracil, tegafur, UFT, doxifluridine, carmofur, galocitabine, emitefur, capecitabine, etc.), aminopterin, nelzarabine, leucoporin calcium, tabloid, butosin, folinate calcium, levofolinate calcium, cladribine, emitefur, fludarabine, gemcitabine, hydroxycarbamide, pentostatin, piritrexim, idoxuridine, mitoguazone, tiazofurin, ambamustine, bendamustine, and DDS formulations thereof.

[0203] Examples of "anticancer antibiotics" include actinomycin D, actinomycin C, mitomycin C, chromomycin A3, bleomycin hydrochloride, bleomycin sulfate, peplomycin sulfate, daunorubicin hydrochloride, doxorubicin hydrochloride, aclarubicin hydrochloride, pirarubicin hydrochloride, epirubicin hydrochloride, neocarzinostatin, mithramycin, sarkomycin, carzinophilin, mitotane, zorubicin hydrochloride, mitoxantrone hydrochloride, idarubicin hydrochloride, eribulin, and DDS preparations thereof.

[0204] Examples of "plant-derived anticancer agents" include etoposide, etoposide phosphate, vinblastine sulfate, vincristine sulfate, vindesine sulfate, teniposide, paclitaxel, docetaxel, DJ-927, vinorelbine, irinotecan, topotecan, and DDS formulations thereof.

[0205] Examples of "molecular targeted therapeutic agents" include imatinib, gefitinib, erlotinib, sorafenib, dasatinib, sunitinib, nilotinib, lapatinib, pazopanib, ruxolitinib, crizotinib, vemurafenib, vandetanib, ponatinib, cabozantinib, tofacitinib, regorafenib, bosutinib, axitinib, dabrafenib, trametinib, nintedanib, idelalisib, ceritinib, lenvatinib, palbociclib, alectinib, afatinib, osimertinib, ribociclib, abemaciclib, and brigadimin. These include tinib, neratinib, copanlisib, cobimetinib, ibrutinib, acalabrutinib, encorafenib, binimetinib, baricitinib, fostamatinib, lorlatinib, erdafitinib, entrectinib, dacomitinib, sirolimus, everolimus, temsirolimus, olaparib, rucaparib, niraparib, venetoclax, azacitidine, decitabine, vorinostat, panobinostat, tazemetostat, romidepsin, bortezomib, carfilzomib, larotrectinib, and ixazomib.

[0206] "Immunomodulators" include, for example, lenalidomide and pomalidomide.

[0207] Examples of "other chemotherapeutic agents" include sobuzoxane.

[0208] Examples of "immunotherapeutic agents (BRM)" include picibanil, krestin, sizofiran, lentinan, ubenimex, interferon, interleukin, macrophage colony-stimulating factor, granulocyte colony-stimulating factor, erythropoietin, lymphotoxin, BCG vaccine, Corynebacterium parvum, levamisole, polysaccharide K, procodazole, anti-CTLA4 antibody, anti-PD-1 antibody, anti-PD-L1 antibody, and Toll-like receptor agonists (e.g., TLR7 agonist, TLR8 agonist, TLR9 agonist, etc.).

[0209] The cell growth factor in the agent that inhibits the action of cell growth factors and their receptors may be any substance that promotes cell growth, and examples thereof include peptides with a molecular weight of 20,000 or less that exert their effects at low concentrations by binding to receptors. Specific examples include epidermal growth factor (EGF) or substances with substantially the same activity as EGF (e.g., TGFalpha), insulin or substances with substantially the same activity as insulin (e.g., insulin, IGF (insulin-like growth factor)-1, IGF-2), fibroblast growth factor (FGF) or substances with substantially the same assay as FGF (e.g., acidic FGF, basic FGF, keratinocyte growth factor KGK), and the like. growth factor, FGF-10, etc.), and other cell growth factors (e.g., CSF (colony stimulating factor), EPO (erythropoietin), IL-2 (interleukin-2), NGF (nerve growth factor), PDGF (platelet-derived growth factor), etc. d growth factor), TGF-beta (transforming growth factor beta), HGF (hepatocyte growth These include vascular endothelial growth factor (VEGF), heregulin, and angiopoietin.

[0210] "SMARC-deficient cancer" refers to cancer in which the SMARC gene is defective and / or expression of the SMARC protein is deleted or attenuated. Preferably, it is cancer in which the SMARC gene is deleted and / or expression of the SMARC protein is deleted. More preferably, it is cancer in which the SMARCB1 gene, SMARCA2 gene, SMARCA4 gene, or SMARCA2 / A4 gene is deleted. Specific examples of SMARC-deficient cancer include malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordomatoid meningioma, neuroepithelial tumor, glioneuronal tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraskeletal myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, paranasal sinus basaloid carcinoma, esophageal adenocarcinoma, papillary thyroid carcinoma, follicular thyroid carcinoma, gastrointestinal stromal tumor, pancreatic undifferentiated rhabdoid tumor, gastrointestinal rhabdoid tumor, renal medullary carcinoma, Examples of such cancers include endometrial cancer, myoepithelioma-like tumors of the female vulva, colorectal cancer, mesothelioma, lung adenocarcinoma, large cell lung carcinoma, lung neuroendocrine tumor, esophageal cancer, gastroesophageal junction cancer, stomach cancer, bladder cancer, squamous cell lung carcinoma, pancreatic cancer, medulloblastoma, clear cell renal carcinoma, liver cancer, ovarian small cell carcinoma, ovarian mucinous tumor, endometrial cancer, uterine sarcoma, nasal and paranasal cancer, thoracic sarcoma, pulmonary pleomorphic carcinoma, thoracic sarcoma, ovarian small cell carcinoma, primary gallbladder tumor, and uterine sarcoma. Preferred are malignant rhabdoid tumor and lung adenocarcinoma.

[0211] "SMARCB1-deficient cancer" refers to cancer in which the SMARCB1 gene is defective and / or expression of the SMARCB1 protein is deleted or attenuated. Preferably, it is cancer in which the SMARCB1 gene is deleted and / or expression of the SMARCB1 protein is deleted. More preferably, it is cancer in which the SMARCB1 gene is deleted. Specific examples include malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordoma-like meningioma, neuroepithelial tumor, glioneuronal tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraskeletal myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, paranasal sinus basaloid carcinoma, esophageal adenocarcinoma, papillary thyroid carcinoma, follicular thyroid carcinoma, gastrointestinal stromal tumor, pancreatic undifferentiated rhabdoid tumor, gastrointestinal rhabdoid tumor, renal medullary cancer, endometrial cancer, myoepithelioma-like tumor of the female vulva, colorectal cancer, and mesothelioma. Preferably, the tumor is malignant rhabdoid tumor.

[0212] "SMARCA2-deficient cancer" refers to cancer in which the SMARCA2 gene is defective and / or expression of the SMARCA2 protein is deleted or attenuated. Preferably, it is cancer in which the SMARCA2 gene is deleted and / or expression of the SMARCA2 protein is deleted. More preferably, it is cancer in which the SMARCA2 gene is deleted. Specific examples include lung adenocarcinoma, lung large cell carcinoma, lung neuroendocrine tumor, esophageal cancer, gastroesophageal junction cancer, and malignant rhabdoid tumor. Preferably, it is lung adenocarcinoma.

[0213] "SMARCA4-deficient cancer" refers to cancer in which the SMARCA4 gene is defective and / or expression of the SMARCA4 protein is deleted or attenuated. Preferably, it is cancer in which the SMARCA4 gene is deleted and / or expression of the SMARCA4 protein is deleted. More preferably, it is cancer in which the SMARCA4 gene is deleted. Specific examples include lung adenocarcinoma, esophageal cancer, gastroesophageal junction cancer, gastric cancer, bladder cancer, lung squamous cell carcinoma, pancreatic cancer, medulloblastoma, renal clear cell carcinoma, liver cancer, ovarian small cell carcinoma, ovarian mucinous tumor, endometrial cancer, uterine sarcoma, nasal and paranasal cancer, rhabdoid tumor, and thoracic sarcoma. Preferably, it is lung adenocarcinoma.

[0214] "SMARCA2 / A4 deficient cancer" refers to cancers that are caused by the SMARCA2 gene and the SMARCA4 gene. The cancer is one in which the gene is deleted and / or the expression of the SMARCA2 protein and the SMARCA4 protein is deleted or attenuated. Preferably, the cancer is one in which the SMARCA2 gene and the SMARCA4 gene are deleted and / or the expression of the SMARCA2 protein and the SMARCA4 protein is deleted. More preferably, the cancer is one in which the SMARCA2 gene and the SMARCA4 gene are deleted. Specific examples include lung adenocarcinoma, lung pleomorphic carcinoma, lung large cell carcinoma, esophageal cancer, gastroesophageal junction cancer, breast sarcoma, ovarian small cell carcinoma, primary gallbladder tumor, uterine sarcoma, malignant rhabdoid tumor, ovarian granulosa tumor, adrenocortical carcinoma, and small cell lung cancer. Preferably, the cancer is lung adenocarcinoma.

[0215] "ARID-deficient cancer" refers to cancer in which the ARID gene is defective and / or expression of the ARID protein is deleted or attenuated. Preferably, it is cancer in which the ARID gene is deleted and / or expression of the ARID protein is deleted. More preferably, it is cancer in which the ARID1A gene, the ARID1B gene, or the ARID1A / 1B gene is deleted. Specific examples include ovarian cancer, gastric cancer, biliary tract cancer, pancreatic cancer, endometrial cancer, neuroblastoma, colorectal cancer, bladder cancer, liver cancer, melanoma, breast cancer, medulloblastoma, and neuroblastoma. Preferably, it is ovarian cancer.

[0216] "ARID1A-deficient cancer" refers to cancer in which the ARID1A gene is defective and / or expression of the ARID1A protein is deleted or attenuated. Preferably, it is cancer in which the ARID1A gene is deleted and / or expression of the ARID1A protein is deleted. More preferably, it is cancer in which the ARID1A gene is deleted. Specific examples include ovarian cancer, gastric cancer, biliary tract cancer, pancreatic cancer, uterine cancer, neuroblastoma, colorectal cancer, and bladder cancer. Preferably, it is ovarian cancer.

[0217] "ARID1B-deficient cancer" refers to cancer in which the ARID1B gene is defective and / or expression of the ARID1B protein is deleted or attenuated. Preferably, it is cancer in which the ARID1B gene is deleted and / or expression of the ARID1B protein is deleted. More preferably, it is cancer in which the ARID1B gene is deleted. Specific examples include ovarian cancer, colorectal cancer, pancreatic cancer, liver cancer, melanoma, breast cancer, medulloblastoma, uterine cancer, bladder cancer, and gastric cancer. Preferably, it is ovarian cancer.

[0218] "ARID1A / 1B-deficient cancer" refers to cancer in which the ARID1A gene and the ARID1B gene are deficient and / or the expression of the ARID1A protein and the ARID1B protein is deleted or attenuated. Preferably, it is cancer in which the ARID1A gene and the ARID1B gene are deleted and / or the expression of the ARID1A protein and the ARID1B protein is deleted. More preferably, it is cancer in which the ARID1A gene and the ARID1B gene are deleted. Specific examples include ovarian cancer, colorectal cancer, endometrial cancer, neuroblastoma, bladder cancer, and gastric cancer. Preferably, it is ovarian cancer.

[0219] "SS18-SSX fusion cancer" refers to cancer in which the SS18 gene and the SSX gene are fused. Specific examples include synovial sarcoma and Ewing's sarcoma. Synovial sarcoma is preferred.

[0220] "Heart disease" refers to a condition caused by some kind of damage to the heart, resulting in poor blood circulation. Specifically, it includes cardiomyopathy, heart failure, and myocardial infarction.

[0221] "Metabolic diseases" are diseases caused by impaired metabolic function, specifically dyslipidemia and diabetes.

[0222] The administration period of the compound of the present disclosure and the concomitant drug is not limited, and the compound and the concomitant drug are administered to the subject at the same time. The compounds of the present disclosure may be administered simultaneously or at different times. A combination of the compound of the present disclosure and a concomitant drug may also be used. The dosage of the concomitant drug can be appropriately selected based on the clinically used dose. The compounding ratio of the compound of the present disclosure to the concomitant drug can be appropriately selected depending on the administration subject, administration route, target disease, symptoms, combination, etc. For example, when the administration subject is a human, 0.01 to 100 parts by weight of the concomitant drug may be used per 1 part by weight of the compound of the present disclosure. Furthermore, for the purpose of suppressing side effects, the compound of the present disclosure may be used in combination with drugs (concomitant drugs) such as antiemetics, hypnotics, and anticonvulsants.

[0223] In this specification, "or" is used when "at least one or more" of the items listed in the sentence can be employed. The same applies to "alternative." In this specification, when it is stated that "within a range of two values," the range includes the two values ​​themselves.

[0224] All references cited herein, including scientific literature, patents, patent applications, and the like, are incorporated by reference in their entirety to the same extent as if each were specifically set forth.

[0225] The present disclosure has been described above by showing preferred embodiments for ease of understanding. The present disclosure will be described below based on examples. However, the above description and the following examples are provided for illustrative purposes only and are not intended to limit the present disclosure. Therefore, the scope of the present disclosure is not limited to the embodiments or examples specifically described herein, but is limited only by the scope of the claims.

[0226] SEQ ID NO: 1 MAENLLDGPPNPKRAKLSSPGFSANDSTDFGSLFDLENDLPDELIPNGGELGLLNSGNLVPDAASKHKQLSELLRGGSGSSINPGIGNVSASSPVQQGLGGQAQGQPNSANMASLSAMGKSPLSQGDSSAPSLPKQAASTSGPTPAASQALNPQAQKQVGLATSSPATSQTGPGICMNANFNQTHPGLLNSNSGHSLINQASQGQAQVMNGSLGAAGRGRGAGMPYPTPAMQGASSSVLAETLTQVSPQMTGHAGLNTAQAGGMAKMGITGNTSPFGQPFSQAGGQPMGATGVNPQLASKQSMVNSLPTFPTDIKNTSVTNVPNMSQMQTSVGIVPTQAIATGPTADPEKRKLIQQQLVLLLHAHKCQRREQANGEVRACSLPHCRTMKNVLNHMTHCQAGKACQVAHCASSRQIISHWKNCTRHDCPVCLPLKNASDKRNQQTILGSPASGIQNTIGSVGTGQQNATSLSNPNPIDPSSMQRAYAALGLPYMNQPQTQLQPQVPGQQPAQPQTHQQMRTLNPLGNNPMNIPAGGITTDQQPPNLISESALPTSLGATNPLMNDGSNSGNIGTLSTIPTAAPPSSTGVRKGWHEHVTQDLRSHLVHKLVQAIFPTPDPAALKDRRMENLVAYAKKVEGDMYESANSRDEYYHLLAEKIYKIQKELEEKRRSRLHKQGILGNQPALPAPGAQPPVIPQAQPVRPPNGPLSLPVNRMQVSQGMNSFNPMSLGNVQLPQAPMGPRAASPMNHSVQMNSMGSVPGMAISPSRMPQPPNMMGAHTNNMMAQAPAQSQFLPQNQFPSSSGAMSVGMGQPPAQTGVSQGQVPGAALPNPLNMLGPQASQLPCPPVTQSPLHPTPPPASTAAGMPSLQHTTPPGMTPPQPAAPTQPSTPVSSSGQTPTPTPGSVPSATQTQSTPTVQAAAQAQVTPQPQTPVQPPSVATPQSSQQQPTPVHAQPPGTPLSQAAASIDNRVPTPSSVASAETNSQQPGPDVPVLEMKTETQAEDTEPDPGESKGEPRSEMMEEDLQGASQVKEETDIAEQKSEPMEVDEKKPEVKVEVKEEEESSSNGTASQSTSPSQPRKKIFKPEELRQALMPTLEALYRQDPESLPFRQPVDPQLLGIPDYFDIVKNPMDLSTIKRKLDTGQYQEPWQYVDDVWLMFNNAWLYNRKTSRVYKFCSKLAEVFEQEIDPVMQSLGYCCGRKYEFSPQTLCCYGKQLCTIPRDAAYYSYQNRYHFCEKCFTEIQGENVTLGDDPSQPQTTISKDQFEKKKNDTLDPEPFVDCKECGRKMHQICVLHYDIIWPSGFVCDNCLKKTGRPRKENKFSAKRLQTTRLGNHLEDRVNKFLRRQNHPEAGEVFVRVVASSDKTVEVKPGMKSRFVDSGEMSESFPYRTKALFAFEEIDGVDVCFFGMHVQEYGSDCPPPNTRRVYISYLDSIHFFRPRCLRTAVYHEILIGYLEYVKKLGYVTGHIWACPPSEGDDYIFHCHPPDQKIPKPKRLQEWYKKMLDKAFAERIIHDYKDIFKQATEDRLTSAKELPYFEGDFWPNVLEESIKELEQEEEERKKEESTAASETTEGSQGDSKNAKKKNNKKTNKNKSSISRANKKKPSMPNVSNDLSQKLYATMEKHKEVFFVIHLHAGPVINTLPPIVDPDPLLSCDLMDGRDAFLTLARDKHWEFSSLRRSKWSTLCMLVELHTQGQDRFVYTCNECKHHVETRWHCTVCEDYDLCINCYNTKSHAHKMVKWGLGLDDEGSSQGEPQSKSPQESRRLSIQRCIQSLVHACQCRNANCSLPSCQKMKRVVQHTKGCKRKTNGGCPVCKQLIALCCYHAKHCQENKCPVPFCLNIKHKLRQQQIQHRLQQAQLMRRRMATMNTRNVPQQSLPSPTSAPPGTPTQQPSTPQTPQPPAQPQPSPVSMSPAGFPSVARTQPPTTVSTGKPTSQVPAPPPPAQPPPAAVEAARQIEREAQQQQHLYRVNINNSMPPGRTGMGTPGSQMAPVSLNVPRPNQVSGPVMPSMPPGQWQQAPLPQQQPMPGLPRPVISMQAQAAVAGPRMPSVQPPRSISPSALQDLLRTLKSPSSPQQQQQVLNILKSNPQLMAAFIKQRTAKYVANQPGMQPQPGLQSQPGMQPQPGMHQQPSLQNLNAMQAGVPRPGVPPQQQAMGGLNPQGQALNIMNPGHNPNMASMNPQYREMLRRQLLQQQQQQQQQQQQQQQQQQGSAGMAGGMAGHGQFQQPQGPGGY PPAMQQQQRMQQHLPLQGSSMGQMAAQMGQLGQMGQPGLGADSTPNIQQALQQRILQQQQMKQQIGSPGQPNPMSPQQHMLSGQPQASHLPGQQIATSLSN QVRSPAPVQSPRPQSQPPHSSPSPRIQPQPSPHHVSPQTGSPHPGLAVTMASSIDQGHLGNPEQSAMLPQLNTPSRSALSSELSLVGDTTGDTLEKFVEGL

[0227] SEQ ID NO: 2

[0228] SEQ ID NO: 3 MAENVVEPGPPSAKRPKLSSPALSASASDGTDFGSLFDLEHDLPDELINSTELGLTNGGDINQLQTSLGMVQDAASKHKQLSELLRSGSSPNLNMGVGGPGQVMASQAQQSSPGLGLINSMVKSPMTQAGLTSPNMGMGTSGPNQGPTQSTGMMNSPVNQPAMGMNTGMNAGMNPGMLAAGNGQGIMPNQVMNGSIGAGRGRQNMQYPNPGMGSAGNLLTEPLQQGSPQMGGQTGLRGPQPLKMGMMNNPNPYGSPYTQNPGQQIGASGLGLQIQTKTVLSNNLSPFAMDKKAVPGGGMPNMGQQPAPQVQQPGLVTPVAQGMGSGAHTADPEKRKLIQQQLVLLLHAHKCQRREQANGEVRQCNLPHCRTMKNVLNHMTHCQSGKSCQVAHCASSRQIISHWKNCTRHDCPVCLPLKNAGDKRNQQPILTGAPVGLGNPSSLGVGQQSAPNLSTVSQIDPSSIERAYAALGLPYQVNQMPTQPQVQAKNQQNQQPGQSPQGMRPMSNMSASPMGVNGGVGVQTPSLLSDSMLHSAINSQNPMMSENASVPSLGPMPTAAQPSTTGIRKQWHEDITQDLRNHLVHKLVQAIFPTPDPAALKDRRMENLVAYARKVEGDMYESANNRAEYYHLLAEKIYKIQKELEEKRRTRLQKQNMLPNAAGMVPVSMNPGPNMGQPQPGMTSNGPLPDPSMIRGSVPNQMMPRITPQSGLNQFGQMSMAQPPIVPRQTPPLQHHGQLAQPGALNPPMGYGPRMQQPSNQGQFLPQTQFPSQGMNVTNIPLAPSSGQAPVSQAQMSSSSCPVNSPIMPPGSQGSHIHCPQLPQPALHQNSPSPVPSRTPTPHHTPPSIGAQQPPATTIPAPVPTPPAMPPGPQSQALHPPPRQTPTPPTTQLPQQVQPSLPAAPSADQPQQQPRSQQSTAASVPTPTAPLLPPQPATPLSQPAVSIEGQVSNPPSTSST [Example]

[0229] The present disclosure will be explained in more detail below with reference to Reference Examples, Examples and Test Examples, but the present disclosure is not limited thereto.

[0230] The following abbreviations may be used in this specification: Me: Methyl Et: Ethyl Ph: Phenyl Bn: Benzyl Boc: tert-butoxycarbonyl n-: normal tert-: tertiary- p-:para- Ac: Acetyl dppf: 1,1'-bis(diphenylphosphino)ferrocene X-PHOS: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

[0231] The NMR (Nuclear Magnetic Resonance) data used for compound identification was obtained using a JNM-ECS400 nuclear magnetic resonance spectrometer (400 MHz) manufactured by JEOL Ltd.

[0232] The symbols used in NMR are s for singlet, d for doublet, dd for doublet of doublets, t for triplet, td for doublet of triplets, q for quartet, m for multiplet, br for broad, brs for broad singlet, brm for broad multiplet and J for coupling constant.

[0233] The LC / MS (Liquid Chromatography-Mass Spectrometry) analysis conditions used for compound identification are as follows. Among the observed mass spectrometry values ​​[MS (m / z)], the value corresponding to the monoisotopic mass (accurate mass consisting of only the main isotope) was defined as [M+H]. + , [MH] - Or [M+2H] 2+etc., and retention time is indicated as Rt (min).

[0234] LC / MS measurement method: Detector: ACQUITY (registered trademark) SQ detector (Waters) HPLC: ACQUITY UPLC® system Column: Waters ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm, 2.1 mm × 30 mm) Solvent: Solution A: 0.06% formic acid / H2O, Solution B: 0.06% formic acid / MeCN Gradient condition:0.0-1.3min Linear gradient from B 2% to 96% Flow rate: 0.8 mL / min UV: 220nm and 254nm Column temperature: 40℃

[0235] Reference example 1 N-(4-fluorobenzyl)-2-hydroxy-N-(3-(trifluoromethyl)oxetan-3-yl)acetamide [ka]

[0236] a) Preparation of N-(4-fluorobenzyl)-3-(trifluoromethyl)oxetan-3-amine (compound Y1) 3-(Trifluoromethyl)oxetan-3-amine hydrochloride (10.0 g) was dissolved in chloroform (188 mL), and 4-fluorobenzaldehyde (7.25 mL) and sodium triacetoxyborohydride (22.4 g) 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 resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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). LC-MS ([M+H] + / Rt(min)):250.1 / 0.936

[0237] b) Preparation of 2-(benzyloxy)-N-(4-fluorobenzyl)-N-(3-(trifluoromethyl)oxetan-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 minutes. Benzyloxyacetyl chloride (12.0 mL) was added at 0°C, and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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). LC-MS ([M+H] + / Rt(min)):398.2 / 1.034

[0238] c) Preparation of N-(4-fluorobenzyl)-2-hydroxy-N-(3-(trifluoromethyl)oxetan-3-yl)acetamide Compound Y2 (15.1 g) was dissolved in methanol (127 mL), palladium hydroxide-activated carbon (2.1 g) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere for 4 hours. 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). LC-MS ([M+H] + / Rt(min)):308.1 / 0.745

[0239] Reference examples 2~5 According to the method described in Reference Example 1, the compounds of Reference Examples 2 to 5 were obtained using the corresponding starting compounds. [Table 1]

[0240] Reference example 6 2-Bromo-N-(4-fluorobenzyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)acetamide [ka]

[0241] a) Preparation of 1,1,1-trifluoro-N-(4-fluorobenzyl)-2-methylpropan-2-amine (compound Y3) 1,1,1-Trifluoro-2-methylpropan-2-amine hydrochloride (1.1 g) was dissolved in chloroform (22 mL), and 4-fluorobenzaldehyde (1.08 mL) and sodium triacetoxyborohydride (3.56 g) 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 resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (1.4 g). LC-MS ([M+H] + / Rt(min)):237.2 / 0.957

[0242] b) Preparation of 2-bromo-N-(4-fluorobenzyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)acetamide Compound Y3 (600 mg) was dissolved in chloroform (6 mL), and bromoacetyl chloride (4.3 mL) was 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 ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (160 mg). LC-MS ([M+H] + / Rt(min)):356.1 / 1.091

[0243] Reference example 7 2-chloro-N-(4-fluorobenzyl)-N-(1-methyl-4-(trifluoromethyl)piperidin-4-yl)acetamide [ka]

[0244] a) Preparation of N-(4-fluorobenzyl)-1-methyl-4-(trifluoromethyl)piperidin-4-amine (compound Y4) 1-Methyl-4-(trifluoromethyl)piperidin-4-amine dihydrochloride (500 mg) was dissolved in chloroform (10 mL), and 4-fluorobenzaldehyde (0.25 mL) and sodium triacetoxyborohydride (780 mg) 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 resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (170 mg). LC-MS ([M+H] + / Rt(min)):291.2 / 0.785 b) Preparation of 2-chloro-N-(4-fluorobenzyl)-N-(1-methyl-4-(trifluoromethyl)piperidin-4-yl)acetamide Chloroacetic anhydride (2.50 g) was added to compound Y4 (170 mg), and the mixture was stirred for 2 hours at 130° C. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to obtain the title compound (150 mg). LC-MS ([M+H] + / Rt(min)):367.1 / 0.808

[0245] Reference example 8 (S)-5'-Bromo-3',3'-difluoro-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-2,5-dione [ka]

[0246] a) Preparation of (S)-5'-bromo-2'H-dispiro[imidazolidine-4,1'-indene-3',2"-[1,3]dithiolane]-2,5-dione (compound Y5) (4S)-5'-Bromospiro(imidazolidine-4,1'-indene)-2,3',5(2'H)-trione (30.0 g) was dissolved in chloroform (200 mL), and 1,2-ethanedithiol (9.40 mL) and boron trifluoride diethyl ether complex (7.0 mL) were added at room temperature, followed by stirring at 50°C for 6 hours. Diethyl ether was added to the reaction mixture at 0°C, and the mixture was stirred at 0°C for 30 minutes. The precipitated solid was collected by filtration, washed with diethyl ether, and dried under reduced pressure to obtain the title compound (36.4 g). LC-MS ([M+H] + / Rt(min)):373.0 / 0.836

[0247] b) Preparation of (4S)-2',5'-dibromo-3',3'-difluoro-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-2,5-dione (compound Y6) In a three-neck PFA flask, 1,3-dibromo-5,5-dimethylhydantoin (11.1 g) was dissolved in dichloromethane (150 mL), and hydrogen fluoride pyridine (10.5 mL) was added at 0°C. The mixture was stirred at 0°C for 5 minutes. Compound Y5 (7.20 g) was added at 0°C, and the mixture was stirred at 0°C for 30 minutes. Aqueous sodium thiosulfate solution and 4 mol / L aqueous sodium hydroxide solution were added to the reaction mixture at 0°C, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, and then filtered. The solvent was evaporated under reduced pressure to give the title compound (11.6 g). LC-MS ([M+H] + / Rt(min)):396.9 / 0.862

[0248] c) Preparation of (S)-5'-bromo-3',3'-difluoro-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-2,5-dione Compound Y6 (13.5 g) was dissolved in toluene (200 mL), and tributyltin hydride (9.15 mL) and azobisisobutyronitrile (370 mg) were added at room temperature, followed by stirring at 100°C for 8 hours. The solvent was evaporated under reduced pressure, hexane was added to the residue, and the solid was collected by filtration and dried under reduced pressure. Chloroform (50 mL) and hexane (50 mL) were added to the solid, followed by stirring at 50°C for 1 hour. The precipitated solid was collected by filtration and dried under reduced pressure to obtain the title compound (6.82 g). LC-MS ([M+H] + / Rt(min)):317.0 / 0.771

[0249] Reference example 9 (S)-2-(5'-Bromo-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(4-fluorobenzyl)-N-(3-(trifluoromethyl)oxetan-3-yl)acetamide [ka]

[0250] The compound of Reference Example 1 (200 mg) was dissolved in tetrahydrofuran (3 mL), and (4S)-5'-bromospiro(imidazolidine-4,1'-indene)-2,3',5(2'H)-trione (200 mg), N,N,N',N'-tetramethylazodicarboxamide (140 mg), and tributylphosphine (0.20 mL) were added at 0°C, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over magnesium sulfate. It was then filtered off, 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 (250 mg). LC-MS ([M+H] + / Rt(min)):584.3 / 1.006

[0251] Reference examples 10~13 According to the method described in Reference Example 9, the compounds of Reference Examples 10 to 13 were obtained using the corresponding starting compounds. [Table 2]

[0252] Reference example 14 2-((3'R,4S)-5'-Bromo-3'-hydroxy-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(4-fluorobenzyl)-N-(1,1,1-trifluoro-2-methylpropan-2-yl)acetamide [ka]

[0253] The compound of Reference Example 6 (310 mg) was dissolved in N,N-dimethylformamide (4 mL), and the solution was mixed with (4S)-5'-bromospiro(imidazolidine-4,1'-indene)-2,3',5(2'H)-trione (220 mg) and tetrabutylammonium iodide (27 mg). and cesium carbonate (470 mg) were added at room temperature and stirred for 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over magnesium sulfate, then filtered, 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 (140 mg). LC-MS ([M+H] + / Rt(min)):570.3 / 1.110

[0254] Reference example 15 (S)-2-(5'-Bromo-2,3'5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(4-fluorobenzyl)-N-(1-methyl-4-(trifluoromethyl)piperidin-4-yl)acetamide [ka]

[0255] The compound of Reference Example 7 (150 mg) was dissolved in N,N-dimethylformamide (2 mL), and (4S)-5'-bromospiro(imidazolidine-4,1'-indene)-2,3',5(2'H)-trione (110 mg), tetrabutylammonium iodide (6 mg), and cesium carbonate (240 mg) were added at room temperature, followed by stirring for 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (52 mg). LC-MS ([M+H] + / Rt(min)):625.2 / 1.179

[0256] Reference example 16 2-(6-bromo-1,1-dioxo-2',5'-dioxo-2H-spiro[benzo[b]thiophene-3,4'-imidazolidine]-1'-yl)-N-(4-fluorobenzyl)-N-(1-trifluoromethyl)cyclopropyl)acetamide [ka]

[0257] The compound of Reference Example 2 (1.2 g) was dissolved in toluene (10 mL), and 6-bromo-2H-spiro[benzo[b]thiophene-3,4'-imidazolidine]-2,5'-dione 1,1-dioxide (1.2 g) and cyanomethylenetributylphosphorane (2.7 g) were added. The mixture was added at 0°C and stirred under reflux for 12 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over magnesium sulfate. The organic layer was then filtered off, 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 (1.0 g). LC-MS ([M+H] + / Rt(min)):604.1 / 1.056

[0258] Reference example 17 tert-Butyl 3-(2-(6-bromo-1,1-dioxide-2',5'-dioxo-2H-spiro[benzo[b]thiophene-3,4'-imidazolidine]-1'-yl)-N-(4-fluorobenzyl)acetamido)-3-(trifluoromethyl)azetidine-1-carboxylate [ka]

[0259] The compound of Reference Example 5 (800 mg) was dissolved in tetrahydrofuran (9 mL), and 6-bromo-2H-spiro[benzo[b]thiophene-3,4'-imidazolidine]-2,5'-dione 1,1-dioxide (620 mg), N,N,N',N'-tetramethylazodicarboxamide (390 mg), and tributylphosphine (0.46 mL) were added at 0°C, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, which was then extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (840 mg). LC-MS ([M+H] + / Rt(min)):721.2 / 1.136

[0260] Reference example 18 (S)-2-(5'-Bromo-3,3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(4-fluorobenzyl)-N-(3-(trifluoromethyl)oxetan-3-yl)acetamide [ka]

[0261] The compound of Reference Example 1 (7.3 g) was dissolved in tetrahydrofuran (118 mL). Compound 8 (8.3 g), N,N,N',N'-tetramethylazodicarboxamide (6.1 g), and tributylphosphine (8.9 mL) were added at 0°C and stirred at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over magnesium sulfate. The organic layer was then filtered off, 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 (8.7 g). LC-MS ([M+H] + / Rt(min)):606.1 / 1.077

[0262] Reference examples 19~21 According to the method described in Reference Example 18, the compounds of Reference Examples 19 to 21 were obtained using the corresponding starting compounds. [Table 3]

[0263] Reference example 22 4-Bromo-1-(2-(3-methoxyazetidin-1-yl)-1H-pyrazole [ka]

[0264] 2-(4-Bromo-1H-pyrazol-1-yl)acetaldehyde (189 mg) was dissolved in chloroform (5 mL), and 3-methoxyazetidine hydrochloride (247 mg) and sodium triacetoxyborohydride (424 mg) were added at 0°C, followed by stirring at room temperature for 20 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated sodium chloride solution. The residue was purified by silica gel column chromatography (ethyl acetate / methanol) to give the title compound (170 mg). LC-MS ([M+H] + / Rt(min)):260.1 / 0.458

[0265] Reference example 23 4-Bromo-1-(1-cyclobutylazetidin-3-yl)-1H-pyrazole [ka]

[0266] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (500 mg) was dissolved in chloroform (10 mL), and cyclobutanone (0.32 mL), acetic acid (0.60 mL), and sodium triacetoxyborohydride (1.1 g) were added at 0°C. The mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (500 mg). LC-MS ([M+H] + / Rt(min)):256.1 / 0.556

[0267] Reference example 24 (R)-1-(4-Bromo-1H-pyrazol-1-yl)-N,N-dimethylpropan-2-amine [ka]

[0268] a) Preparation of tert-butyl (R)-(1-(4-bromo-1H-pyrazol-1-yl)propan-2-yl)(methyl)carbamate (compound Y7) N-Boc-(R)-2-(methylamino)propan-1-ol (730 mg) was dissolved in toluene (10 mL), 4-bromopyrazole (567 mg) and cyanomethylenetributylphosphorane (1.9 g) were added at room temperature, and the mixture was stirred under reflux for 2 hours. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (700 mg). LC-MS ([M+H] + / Rt(min)):318.1 / 0.982

[0269] b) Preparation of (R)-1-(4-bromo-1H-pyrazol-1-yl)-N,N-dimethylpropan-2-amine Compound Y7 (700 mg) was dissolved in chloroform (10 mL), trifluoroacetic acid (10 mL) was added at room temperature, and the mixture was stirred for 1 hour. The reaction mixture was evaporated under reduced pressure, and then dissolved in tetrahydrofuran (10 mL). Formaldehyde (0.33 mL) and sodium triacetoxyborohydride (1.4 g) were added at 0°C, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, and then filtered off, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (500 mg). LC-MS ([M+H] + / Rt(min)):232.1 / 0.441

[0270] Reference example 25 4-Bromo-1-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazole [ka]

[0271] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (1.0 g) was dissolved in chloroform (21 mL), and 3-oxetanone (0.49 mL), acetic acid (1.2 mL), and sodium triacetoxyborohydride (2.8 g) were added at 0°C. The mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (920 mg). LC-MS ([M+H] + / Rt(min)):258.0 / 0.489

[0272] Reference example 26 1-(1-arylazetidin-3-yl)-4-bromo-1H-pyrazole [ka]

[0273] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (300 mg) was dissolved in tetrahydrofuran (10 mL), and triethylamine (1.0 mL) and allyl bromide (0.15 mL) were added at 0°C. The mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (300 mg). LC-MS ([M+H] + / Rt(min)):242.0 / 0.494

[0274] Reference example 27 4-Bromo-1-(1-(2,2-difluoroethyl)azetidin-3-yl)-1H-pyrazole [ka]

[0275] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (500 mg) was dissolved in tetrahydrofuran (10 mL), and triethylamine (1.7 mL) and 2,2-difluoroethyl trifluoromethanesulfonate (583 mg) were added at 0°C. The mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (300 mg). LC-MS ([M+H] + / Rt(min)):266.0 / 0.514

[0276] Reference example 28 4-Bromo-1-(1-(3,3-difluorocyclobutyl)azetidin-3-yl)-1H-pyrazole [ka]

[0277] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (500 mg) was dissolved in chloroform (10 mL), and 3,3-difluorocyclobutanone (394 mg) and sodium triacetoxyborohydride (1.6 g) were added at 0°C. The mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (200 mg). LC-MS ([M+H] + / Rt(min)):292.0 / 0.616

[0278] Reference example 29 2-(3-(4-bromo-1H-pyrazol-1-yl)-1-methylazetidin-3-yl)acetonitrile [ka]

[0279] a) Preparation of tert-butyl 3-(4-bromo-1H-pyrazol-1-yl)-3-(cyanomethyl)azetidine-1-carboxylate (compound Y8) tert-Butyl 3-(cyanomethylene)azetidine-1-carboxylate (1.2 g) was dissolved in acetonitrile (20 mL), and 4-bromopyrazole (798 mg) and diazabicycloundecene (2.4 mL) were added at room temperature, followed by stirring for 2 hours. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (1.2 g). LC-MS ([M-tBu] + / Rt(min)):285.0 / 0.972

[0280] b) Preparation of 2-(3-(4-bromo-1H-pyrazol-1-yl)-1-methylazetidin-3-yl)acetonitrile Hydrogen chloride (4 mol / L in 1,4-dioxane, 5 mL) was added to compound Y8 (1.2 g) at room temperature and stirred for 2 hours. The reaction mixture was evaporated under reduced pressure and dissolved in chloroform / methanol (10 / 2 mL). Formaldehyde (0.43 mL) and sodium triacetoxyborohydride (449 mg) were added at 0°C and stirred at room temperature for 20 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (302 mg). LC-MS ([M+H] + / Rt(min)):255.0 / 0.411 Reference example 30 (S)-1-(4-Bromo-1H-pyrazol-1-yl)-N,N-dimethylpropan-2-amine [ka]

[0281] According to the same procedure as in Reference Example 24, the title compound (210 mg) was obtained. LC-MS ([M+H] + / Rt(min)):232.1 / 0.432

[0282] Reference example 31 4-Bromo-1-(1-(cyclopropylazetidin-3-yl)-1H-pyrazole [ka]

[0283] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (500 mg) was dissolved in chloroform (10 mL), and (1-ethoxycyclopropoxy)trimethylsilane (1.5 g) and sodium cyanoborohydride (1.3 g) were added at 0°C, followed by stirring at 60°C for 2 hours. Water was added to the reaction mixture, which was then extracted twice with ethyl acetate. The resulting organic layer The extract was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (444 mg). LC-MS ([M+H] + / Rt(min)):242.0 / 0.484

[0284] Reference example 32 4-Bromo-1-((3-fluoro-1-methylazetidin-3-yl)methyl)-1H-pyrazole [ka]

[0285] a) Preparation of tert-butyl 3-((4-bromo-1H-pyrazol-1-yl)methyl)-3-fluoroazetidine-1-carboxylate (compound Y10) 1-Boc-3-fluoroazetidine-3-methanol (1.5 g) was dissolved in toluene (20 mL), and 4-bromopyrazole (1.0 g) and cyanomethylenetributylphosphorane (3.6 mL) were added at room temperature, and the mixture was stirred under reflux for 2 hours. The residue was purified by silica gel column chromatography (hexane / ethyl acetate) to give the title compound (2.0 g). LC-MS ([M+H] + / Rt(min)):334.1 / 1.007

[0286] b) Preparation of 4-bromo-1-((3-fluoro-1-methylazetidin-3-yl)methyl)-1H-pyrazole Hydrogen chloride (4 mol / L in 1,4-dioxane, 5 mL) was added to compound Y10 (1.0 g) at room temperature and stirred for 2 hours. The reaction mixture was evaporated under reduced pressure and dissolved in chloroform / methanol (12 / 3 mL). Formaldehyde (0.73 mL) and sodium triacetoxyborohydride (761 mg) were added at 0°C and stirred at room temperature for 20 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (550 mg). LC-MS ([M+H] + / Rt(min)):248.0 / 0.429

[0287] Reference example 33 4-(4-Bromo-1H-pyrazol-1-yl)-1-(oxetan-3-yl)piperidine [ka]

[0288] 4-(4-Bromo-1H-pyrazol-1-yl)piperidine hydrochloride (504 mg) was dissolved in chloroform (11 mL), and 3-oxetanone (0.26 mL), acetic acid (0.63 mL), and sodium triacetoxyborohydride (1.2 g) were added at 0°C. The mixture was stirred at room temperature for 20 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (610 mg). LC-MS ([M+H] + / Rt(min)):286.0 / 0.489

[0289] Reference example 34 4-Bromo-1-(1-propargylazetidin-3-yl)-1H-pyrazole [ka]

[0290] 1-(Azetidin-3-yl)-4-bromo-1H-pyrazole hydrochloride (500 mg) was dissolved in tetrahydrofuran (10 mL), and triethylamine (1.7 mL) and propargyl bromide (0.35 mL) were added at 0°C. The mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (300 mg). LC-MS ([M+H] + / Rt(min)):240.0 / 0.515

[0291] Example 1 N-[(4-Fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide [ka]

[0292] The compound of Reference Example 9 (67 mg) was dissolved in 1,2-dimethoxyethane (1 mL) and water (0.3 mL), and potassium carbonate (37 mg), 1-(2-morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol ester (66 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (10 mg) were added at room temperature, followed by stirring at 90°C for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, and then filtered to remove the solvent. The residue was purified by silica gel column chromatography (ethyl acetate / methanol) to obtain the title compound (42 mg). LC-MS ([M+H] + / Rt(min)):685.5 / 0.885

[0293] Examples 2 to 11 According to the method described in Example 1, the compounds of Examples 2 to 11 were obtained using the corresponding compounds of Reference Examples and commercially available compounds as raw materials. [Table 4-1] [Table 4-2]

[0294] Example 12 2-{(1'S)-5'-[1-(1-cyanocyclopropyl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide [ka]

[0295] a) Preparation of (S)-2-(5'-bromo-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-(4-fluorobenzyl-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Compound Y11) The compound of Reference Example 13 (688 mg) was dissolved in chloroform (5 mL), and trifluoroacetic acid (2 mL) was added at room temperature, followed by stirring for 1 hour. The reaction mixture, which had been evaporated under reduced pressure, was dissolved in chloroform (5 mL), and acetic acid (0.58 mL), formaldehyde (0.23 mL), and sodium triacetoxyborohydride (747 mg) were added at 0°C, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (601 mg). LC-MS ([M+H] + / Rt(min)):597.2 / 0.890

[0296] b) Preparation of Example 12 1-(4-Bromo-1H-pyrazol-1-yl)cyclopropane-1-carbonitrile (100 mg) was dissolved in 1,4-dioxane (2 mL). Potassium acetate (139 mg), X-PHOS (15 mg), bis(pinacolato)diboron (240 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (26 mg) were added at room temperature and stirred at 100°C for 1 hour. Water (0.3 mL), potassium carbonate (87 mg), and compound Y11 (188 mg) were added to the reaction mixture at room temperature and stirred at 100°C for 2 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, 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 (49 mg). LC-MS ([M+H] + / Rt(min)):650.3 / 0.840

[0297] Examples 13 to 15 According to the method described in Example 12, the compounds of Examples 13 to 15 were obtained using the corresponding compounds of Reference Examples and commercially available compounds as starting materials. [Table 5]

[0298] Example 16 2-{(1'S)-5'-[1-(1-cyclobutylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide [ka]

[0299] The compound of Reference Example 23 (190 mg) was dissolved in 1,4-dioxane (2 mL). Potassium acetate (146 mg), X-PHOS (24 mg), bis(pinacolato)diboron (213 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (40 mg) were added at room temperature, and the mixture was stirred at 100°C for 1 hour. Water (0.4 mL), potassium carbonate (137 mg), and the compound of Reference Example 10 (281 mg) were added to the reaction mixture at room temperature, and the mixture was stirred at 100°C for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, 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 (50 mg). LC-MS ([M+H] + / Rt(min)):665.4 / 1.011

[0300] Examples 17 to 31 According to the method described in Example 16, the compounds of Examples 17 to 31 were obtained using the corresponding compounds of Reference Examples as starting materials. [Table 6-1] [Table 6-2] [Table 6-3]

[0301] Example 32 2-[(1'S)-3',3'-Difluoro-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide [ka]

[0302] The compound of Reference Example 19 (108 mg) was dissolved in 1,2-dimethoxyethane (0.9 mL) and water ( The residue was dissolved in 0.2 mL of ethyl acetate, and potassium carbonate (51 mg), 1-(2-morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol ester (84 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (15 mg) were added at room temperature, followed by stirring at 90°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine and dried over sodium sulfate. It was then filtered off, 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 (50 mg). LC-MS ([M+H] + / Rt(min)):691.6 / 0.935 1H-NMR(400MHz,CDCl3):δ8.00-7.80(1H, br),7.81-7.42 (5H, m), 7.13-6.98 (3H, m), 6.92 (1H, t, J = 8.9 Hz), 5.84(1H, d, J = 23.2 Hz), 5.18 (1H, t, J = 14.6 Hz), 4.81-4.62 (2H, m), 4.37 (1H,d, J = 15.9 Hz), 4.00-3.70 (4H, m), 3.37-3.27 (2H, m), 3.00-2.50 (6H, m),1.87-1.65 (2H, m), 1.35-1.10 (2H, m).

[0303] Examples 33 to 43 According to the method described in Example 32, the compounds of Examples 33 to 43 were obtained using the corresponding compounds of Reference Examples and commercially available compounds as starting materials. [Table 7-1] [Table 7-2] [Table 7-3]

[0304] Example 44 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-methyl ethyl-3-(trifluoromethyl)azetidin-3-yl]acetamide [ka]

[0305] a) Preparation of (S)-2-(5'-bromo-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-(4-fluorobenzyl-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide (Compound Y12) The compound of Reference Example 21 (241 mg) was dissolved in chloroform (3 mL), trifluoroacetic acid (1 mL) was added at room temperature, and the mixture was stirred for 3 hours. The reaction mixture was evaporated under reduced pressure, dissolved in chloroform (3 mL), and formaldehyde (0.10 mL) and sodium triacetoxyborohydride (145 mg) were added at 0°C, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (208 mg). LC-MS ([M+H] + / Rt(min)):619.2 / 0.913

[0306] b) Preparation of Example 44 Compound Y12 (100 mg) was dissolved in 1,2-dimethoxyethane (0.7 mL) and water (0.1 mL). Potassium carbonate (45 mg), 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (50 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (13 mg) were added at room temperature and stirred at 90°C for 1 hour. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, 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 (51 mg). LC-MS ([M+H] + / Rt(min)):621.3 / 0.816

[0307] Example 45 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-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 [ka]

[0308] According to the method described in Example 44, the title compound was obtained using the compound of Reference Example 21 and commercially available compounds as starting materials. LC-MS ([M+H] + / Rt(min)):674.4 / 0.913 1H-NMR (400MHz, DMSO-d6):δ9.01 (1H, s), 8.72 (1H, s), 8.24 (1H, s), 8.01-7.95 (2H, m),7.46-7.42 (3H, m), 7.29 (2H, t, J = 8.8 Hz), 4.72 (2H, br), 4.16 (2H, br), 3.73(2H, br), 3.25-3.05 (3H, m), 2.87-2.76 (1H, m), 2.18 (3H, s), 2.03 (6H, s).

[0309] Example 46 2-[(1'S)-3',3'-Difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide [ka]

[0310] The compound of Reference Example 25 (128 mg) was dissolved in 1,4-dioxane (1.4 mL), and potassium acetate (97 mg), X-PHOS (31 mg), bis(pinacolato)diboron (142 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (27 mg) were added at room temperature, followed by stirring at 100°C for 1 hour. Water (0.3 mL), potassium carbonate (91 mg), and the compound of Reference Example 18 (200 mg) were added to the reaction mixture at room temperature, followed by stirring at 100°C for 3 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / methanol) to yield the title compound (57 mg). LC-MS ([M+H] + / Rt(min)):705.4 / 0.885 1H-NMR (400 MHz, DMSO-d6):δ9.00 (1H,s), 8.56 (1H, s), 8.11 (1H, s), 7.92 (2H, d, J = 8.0 Hz), 7.48-7.44 (2H, m),7.39 (1H, d, J = 8.0 Hz), 7.31-7.27 (2H, m), 5.0 (1H, t, J = 7.2 Hz), 4.79-4.67(6H, m), 4.61-4.58 (1H, m), 4.45-4.43 (1H, m), 4.19-4.06 (2H, m), 3.87-3.83 (1H, m), 3.76-3.72 (2H, m), 3.57-3.53 (2H, m).

[0311] Examples 47 to 51 According to the method described in Example 46, the compounds of Examples 47 to 51 were obtained using the corresponding compounds of Reference Examples as starting materials. [Table 8-1] [Table 8-2]

[0312] Example 52 2-{(1'S)-5'-[1-(azetidin-3-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide [ka]

[0313] a) Preparation of 2-{(1'S)-5'-[1-(N-Boc-azetidin-3-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide (compound Y13) The compound of Reference Example 19 (100 mg) was dissolved in 1,2-dimethoxyethane (0.9 mL) and water (0.2 mL), and potassium carbonate (47 mg), tert-butyl 3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)azetidine-1-carboxylate (89 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (14 mg) were added at room temperature, followed by stirring at 90°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine and dried over sodium sulfate, then filtered off, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound (72 mg). LC-MS ([M-tBu] + / Rt(min)):677.3 / 1.228

[0314] b) Preparation of Example 52 Compound Y13 (72 mg) was dissolved in chloroform (2 mL), trifluoroacetic acid (0.5 mL) was added at room temperature, and the mixture was stirred for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform / methanol) to give the title compound (80 mg). LC-MS ([M+H] + / Rt(min)):634.0 / 1.097 1H-NMR (400MHz, DMSO-d6):δ9.07-9.00 (1H, m), 8.53-8.51 (1H, m), 8.11-8.09 (1H, m),7.97-7.89 (2H, m), 7.47-7.38 (1H, m), 7.27-7.06 (4H, m), 5.15 (1H, m),4.85-4.42 (4H, m), 3.94-3.91 (2H, m), 3.77-3.73 (2H, m),3.20-3.05 (1H, m), 2.84(1H, q, J = 14.0 Hz), 2.05-1.72 (2H, m), 1.34-1.05 (2H, m).

[0315] Example 53 2-{(1'S)-5'-[2-(dimethylamino)ethoxy]-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide [ka]

[0316] Copper iodide (47 mg) and N,N-dimethylethanolamine (588 mg) were added to the compound of Reference Example 18 (50 mg) at room temperature, and the mixture was stirred under microwave irradiation at 140° C. for 2 hours. The reaction mixture was purified by amino silica gel column chromatography (ethyl acetate / methanol) to obtain the title compound (10 mg). LC-MS ([M+H] + / Rt(min)):615.3 / 1.010

[0317] Example 54 2-[(1'S)-3',3'-difluoro-5'-(3-methoxyazetidin-1-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide [ka]

[0318] The compound of Reference Example 18 (50 mg) was dissolved in 1,4-dioxane (1.0 mL), and cesium carbonate (107 mg), X-PHOS (12 mg), 3-methoxyazetidine hydrochloride (15 mg), and tris(dibenzylideneacetone)dipalladium(0) (8 mg) were added at room temperature, followed by stirring at 100°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over magnesium sulfate. It was then filtered off, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound (10 mg). LC-MS ([M+H] + / Rt(min)):613.3 / 1.010 1H-NMR (400MHz, DMSO-d6): δ8.88 (1H, s), 7.45 (2H, dd, J = 8.5, 4.9 Hz), 7.29 (2H, t, J =8.8 Hz), 7.16 (1H, d, J = 8.5 Hz), 6.69 (1H, d, J = 6.7 Hz), 6.54 (1H, s),4.82-4.60 (6H, m), 4.33-4.28 (1H, m), 4.21-4.05 (4H, m), 3.67-3.63 (2H, m),3.23 (3H, s), 3.02 (1H, td, J = 15.4, 6.5 Hz), 2.68 (1H, q, J = 15.4 Hz).

[0319] Example 55 2-[(1'S)-3',3'-difluoro-5'-(3-methoxypiperidin-1-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide [ka]

[0320] According to the method described in Example 54, the title compound was obtained using the compound of Reference Example 18 and commercially available compounds as starting materials. LC-MS ([M+H] + / Rt(min)):641.4 / 1.018 1H-NMR (400MHz, CDCl3):δ7.42-7.40 (2H, m), 7.31-7.30 (1H, m), 7.20-7.13 (3H, m), 7.04-7.02(1H, br m), 5.70-5.66 (1H, m), 4.88-4.80 (4H, m), 4.53 (2H, s), 4.19 (2H, s),3.67-3.64 (1H, m), 3.42-3.41 (4H, m), 3.26-3.19 (1H, m), 3.00-2.85 (2H, m),2.75-2.72 (1H, m), 2.07-2.02 (1H, m), 1.90-1.84 (1H, m), 1.66-1.63 (1H, m),1.53-1.44 (1H, m), 1.31-1.19 (1H, m)

[0321] Example 56 N-[(4-Fluorophenyl)methyl]-2-[(1'S)-3'-methylidene-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide [ka]

[0322] a) Preparation of tert-butyl (S)-3-(2-{5'-bromo-3'-methylene-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}-N-(4-fluorobenzyl)acetamido)-3-(trifluoromethyl)azetidine-1-carboxylate (Compound Y14) Methyltriphenylphosphonium iodide (852 mg) was dissolved in tetrahydrofuran (9 mL), and potassium tert-butoxide (296 mg) was added at room temperature, followed by stirring for 30 minutes. The compound of Reference Example 13 (1.20 g) was added at room temperature, followed by stirring under reflux for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound. A compound (800 mg) was obtained. LC-MS ([M-tBu]+ / Rt(min)):625.1 / 1.214

[0323] b) Preparation of tert-butyl (S)-3-(N-(4-fluorobenzyl)-2-{5'-(1-methyl-1H-pyrazol-4-yl)-3'-methylene-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-indene]-1-yl}acetamido)-3-(trifluoromethyl)azetidine-1-carboxylate (Compound Y15) Compound Y14 (800 mg) was dissolved in 1,2-dimethoxyethane (4.9 mL) and water (1.0 mL). Potassium carbonate (324 mg), 1-methyl-1H-pyrazole-4-boronic acid pinacol ester (366 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (96 mg) were added at room temperature and stirred at 90°C for 1 hour. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound (600 mg). LC-MS ([M+H] + / Rt(min)):683.5 / 1.094

[0324] c) Preparation of Example 56 Compound Y15 (241 mg) was dissolved in chloroform (3 mL), trifluoroacetic acid (3 mL) was added at room temperature, and the mixture was stirred for 1 hour. The reaction mixture was evaporated under reduced pressure, dissolved in chloroform (3 mL), and formaldehyde (0.16 mL) and sodium triacetoxyborohydride (699 mg) were added at 0°C, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, 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 (333 mg). LC-MS ([M+H] + / Rt(min)):597.3 / 0.770

[0325] Example 57 N-[(4-Fluorophenyl)methyl]-2-[(1'S)-3'-methylidene-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide [ka]

[0326] a) Preparation of (S)-2-(5'-bromo-3'-methylene-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl)-N-(4-fluorobenzyl)-N-(1-(trifluoromethyl)cyclopropyl)acetamide (Compound Y16) Methyltriphenylphosphonium iodide (171 mg) was dissolved in tetrahydrofuran (2 mL ), potassium tert-butoxide (59 mg) was added at room temperature, and the mixture was stirred for 30 minutes. The compound of Reference Example 10 (200 mg) was added at room temperature, and the mixture was stirred under reflux for 2 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over sodium sulfate, then filtered off, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound (105 mg). LC-MS ([M+H] + / Rt(min)):566.1 / 1.152

[0327] b) Preparation of Example 57 Compound Y16 (105 mg) was dissolved in 1,2-dimethoxyethane (0.8 mL) and water (0.2 mL). Potassium carbonate (51 mg), 1-(2-morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol ester (85 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (15 mg) were added at room temperature and stirred at 90°C for 4 hours. Water was added to the reaction mixture, which was then extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine, dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to yield the title compound (32 mg). LC-MS ([M+H] + / Rt(min)):667.3 / 0.980

[0328] Example 58 N-[(4-Fluorophenyl)methyl]-2-[(3'S)-6'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2'',5''-dioxo-2'H-dispiro[cyclopropane-1,1'-indene-3',4''-imidazolidine]-1''-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide [ka]

[0329] a) Preparation of (S)-2-(5'-bromo-2",5"-dioxo-2'H-dihydrospiro[cyclopropane-1,3'-indene-1'-4"-imidazolidine]-1"-yl)-N-(4-fluorobenzyl)-N-(1-(trifluoromethyl)cyclopropyl)acetamide (Compound Y17) A 1 mol / L hexane solution (3.4 mL) of diethylzinc was dissolved in dichloromethane (2.0 mL), and chloroiodomethane (0.5 mL) was added at -20°C, followed by stirring for 20 minutes. A dichloromethane solution (4.7 mL) of compound Y16 (380 mg) was added at -20°C, followed by stirring at room temperature for 1 hour. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine, dried over magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to give the title compound (171 mg). LC-MS ([M+H] + / Rt(min)):580.1 / 1.164

[0330] b) Preparation of Example 58 Compound Y17 (171 mg) was dissolved in 1,2-dimethoxyethane (1.2 mL) and water (0. The residue was dissolved in 2 mL of ethyl acetate, and potassium carbonate (81 mg), 1-(2-morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol ester (136 mg), and [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride (24 mg) were added at room temperature, followed by stirring at 90°C for 4 hours. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate. The resulting organic layer was washed with saturated brine and dried over sodium sulfate. It was then filtered off, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate / hexane) to yield the title compound (93 mg). LC-MS ([M+H] + / Rt(min)):681.4 / 0.978

[0331] Example 59 2-[(1'S,3'R)-3'-Fluoro-3'-methyl-5'-(1-methyl-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 [ka]

[0332] a) Preparation of 2-((3'R,4S)-3'-fluoro-3'-(iodomethyl)-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-(4-fluorobenzyl)-N-(1-methyl-3-(trifluoromethyl)azetidin-3-yl)acetamide (Compound Y18) The compound of Example 56 (200 mg) was dissolved in dichloromethane (1.7 mL), and hydrogen fluoride pyridine (99 mg) and N-iodosuccinimide (226 mg) were added at 0°C, followed by stirring at room temperature for 2 hours. Water was added to the reaction mixture, which was then extracted twice with chloroform. The resulting organic layer was washed with saturated brine and dried over sodium sulfate. The organic layer was then filtered off, 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 (249 mg). LC-MS ([M+H] + / Rt(min)):743.2 / 0.895

[0333] b) Preparation of Example 59 Compound Y18 (249 mg) was dissolved in toluene (1.7 mL), and azobisisobutyronitrile (66 mg) and tributyltin hydride (146 mg) were added at room temperature, followed by stirring under reflux for 2 hours. The reaction mixture was purified by aminosilica gel column chromatography (ethyl acetate / hexane) to give the title compound (26 mg). LC-MS ([M+H] + / Rt(min)):617.3 / 0.823

[0334] Comparative Example 1 [ka] The compound of Comparative Example 1 was obtained using the method described in WO2016 / 044770. LC-MS ([M+H] + / Rt(min)):619.4 / 0.938

[0335] Comparative Example 2 [ka] The compound of Comparative Example 2 was obtained using the method described in WO2020 / 108500. LC-MS ([M+H] + / Rt(min)):531.3 / 0.965

[0336] Test Example Test results for representative compounds of the present disclosure are shown below, and the pharmacological characteristics, chemical characteristics, and pharmacokinetics of the compounds are explained, but the present disclosure is not limited to these test examples.

[0337] Test Example 1: HAT activity inhibition experiment The HAT activity inhibitory ability of HAT inhibitors was evaluated using the SensoLyte HAT (p300) Assay Kit (ANASPEC, AS-72172). Specifically, 7.5 μL of each compound from Examples 1 to 59 diluted in assay buffer was added to 7.5 μL of recombinant p300 solution diluted 10-fold with assay buffer and incubated at room temperature for 10 minutes. 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 to the mixture and incubated at 37°C for 30 minutes. 37.5 μL of Stop Solution was added to terminate the reaction. 75 μL of p300 Developer solution diluted 50-fold with assay buffer was added, and the mixture was incubated at room temperature for 30 minutes in the dark. Fluorescence at 513 nm was measured using a multiplate reader when irradiated with 389 nm excitation light. Based on the measured fluorescence intensity, the IC 50The values ​​were calculated. In addition, some of the values ​​were expressed as the enzyme reaction inhibition rate at a compound concentration of 2 μM. The results are shown in Table 9.

[0338] [Table 9]

[0339] As shown in Table 9, a series of compounds of the present disclosure were confirmed to inhibit the function of the HAT domain of P300 / CBP. Among them, Examples 1 to 8, 12 to 14, 16, 21, 23, 26 to 28, 34, 38, 41, 44 to 47, and 51 to 52 particularly showed strong inhibition of HAT activity.

[0340] Test Example 2: Cell proliferation inhibition experiment G-401 cells (derived from malignant rhabdoid tumor) were obtained from the American Type Culture Collection (ATCC) and cultured in McCoy's 5A medium containing 10% fetal bovine serum and 1% penicillin / streptomycin at 37°C in 5% CO2.

[0341] 500 cells were seeded per well on a 384-well plate. One day after seeding, Examples 1 to 59 were added so that the final concentration of DMSO was 0.1%, and the cells were cultured for 3 days. After the culture was completed, the cell viability was measured using CellTiter-Glo Luminescent Cell Viability Assay (Promega, G7570). From the viability curve, the IC, which corresponds to the concentration of the evaluation compound that shows 50% inhibition of cell proliferation, was determined. 50 The values ​​were calculated. In addition, some of the values ​​were expressed as the cell growth inhibition rate at a compound concentration of 1 μM. The results are shown in Table 10.

[0342] [Table 10]

[0343] As shown in Table 10, a series of compounds of the present disclosure exhibited a strong cell growth inhibitory effect on G-401 cells, which are cells derived from malignant rhabdoid tumors. 8, 12-14, 21, 23, 26-27, 34, 38, 41, 43-46, 51 showed strong cell proliferation inhibitory effects.

[0344] Test Example 3: Solution stability test The stability in buffer solutions was evaluated for Examples 32, 46, 51, 57, 58, 59, Comparative Examples 1, and 2. The test compounds were added to buffer solutions of pH 3.0, 4.0, 5.0, 7.4, and 9.0 to a concentration of 10 μmol / L, respectively, and stored in a constant temperature cabinet at 40°C. Measurement was performed by HPLC on the start of storage and after 1 to 7 days of storage, and the purity (area percentage of the compound peak) was determined. The buffer solutions used at each pH are as follows: pH 3.0: 50mmol / L citrate buffer pH 4.0: 50mmol / L citrate buffer pH 5.0: 50mmol / L citrate buffer pH 7.4: 50mmol / L phosphate buffer pH 9.0: 50mmol / L glycine buffer The HPLC measurement conditions are as follows. HPLC conditions Column: Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm Column temperature: 40℃ Mobile phase: A: 0.1% trifluoroacetic acid in water B: Acetonitrile A / B(min):95 / 5(0)→0 / 100(3.5)→0 / 100(4)→95 / 5(4.01)→95 / 5(5) Flow rate: 0.8mL / min Detection: UV-visible detector Measurement wavelength: 254 nm Injection volume: 5μL or Column: Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm Column temperature: 40℃ Mobile phase: A: 0.1% trifluoroacetic acid in water 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: 0.8mL / min Detection: UV-visible detector Measurement wavelength: 254 nm Injection volume: 2~3μL

[0345] The test results are shown in Tables 11 to 19.

[0346] Examples 32, 46, 51, 57 and 58 maintained their purity over 7 days at pH 3 to 5 and were stable in solution.

[0347] The purity of Comparative Example 1, a compound described in WO2016 / 044770, decreased over time at any of pH values ​​of 3.0, 4.0, 5.0, 7.4, and 9.0. Furthermore, in the test of Comparative Example 1, it was revealed that the amount of the hydroxide form of Comparative Example 1 increased as the purity of Comparative Example 1 decreased, as shown in Table 17. This suggests the possibility that the fluorine at the benzyl position of Comparative Example 1 is hydrolyzed to a hydroxyl group in an aqueous solution, generating toxic hydrogen fluoride in the system.

[0348] The compound of Comparative Example 2 described in WO2020 / 108500 was used at pH 7.4 and At pH 9.0 and 9.0, the purity decreased over time.

[0349] The test results show that Examples 32, 46, 51, 57 and 58 have extremely high stability in solution compared to Comparative Examples 1 and 2, and by appropriately adjusting the pH, it is possible to prepare a solution formulation with sufficient stability. [Table 11] [Table 12] [Table 13] [Table 14] [Table 15] [Table 16] [Table 17] [Table 18]

[0350] Hydroxylated form of Comparative Example 1 [ka] LC-MS ([M+H] + / Rt(min)):617.4 / 0.844 [Table 19]

[0351] Test Example 4: Solubility test The solubility was measured for Examples 12, 46, 51, 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 stored in a thermostatic chamber at 5° C. After standing overnight, the mixture was filtered through a membrane filter, and the concentration of the filtrate was measured by HPLC. The HPLC measurement conditions are as follows. HPLC conditions Column: Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm Column temperature: 40℃ Mobile phase: A: 0.1% trifluoroacetic acid in water B: Acetonitrile A / B(min):95 / 5(0)→0 / 100(3.5)→0 / 100(4)→95 / 5(4.01)→95 / 5(5) Flow rate: 0.8mL / min Detection: UV-visible detector Measurement wavelength: 254 nm Injection volume: 5μL or Column: Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm Column temperature: 40℃ Mobile phase: A: 0.1% trifluoroacetic acid in water 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: 0.8mL / min Detection: UV-visible detector Measurement wavelength: 254 nm Injection volume: 2μL or Column: Acquity UPLC BEH C18, 1.7 μm, 50 x 2.1 mm Column temperature: 40℃ Mobile phase: A: 0.1% trifluoroacetic acid in water 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: 0.8mL / min Detection: UV-visible detector Measurement wavelength: 254 nm Injection volume: 3μL

[0352] The test results are shown in Table 20.

[0353] Examples 12, 46, and 51 exhibited good solubility. In particular, Example 46 exhibited high solubility of 5 mg / mL or more at pH 2.0. On the other hand, at pH 2.0 and pH 3.0, Comparative Example 1 exhibited extremely low solubility of 0.002 mg / mL and 0.005 mg / mL, respectively, and Comparative Example 2 also exhibited extremely low solubility of 0.004 mg / mL and 0.005 mg / mL, respectively. The test results indicated that Examples 12, 46, and 51 are compounds that exhibit exceptional effects on solubility. [Table 20]

[0354] Test Example 5: Membrane permeability test

[0355] The membrane permeability of the test compound was tested using the 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 stacked and incubated at 37°C. After incubation for 4 hours at 4°C, the UV absorption of the acceptor and donor solutions was measured using a UV plate reader (190-500 nm). Compounds with poor UV absorption were analyzed by LC-MS. The permeability coefficient Pe (10 -6 The velocity (cm / sec) was calculated using the following formula:

number

[0356] The test results are shown in Table 21.

[0357] In particular, it was revealed that Examples 44, 45, 46, and 51 exhibited good membrane permeability equivalent to that of Comparative Examples 1 and 2. [Table 21]

[0358] Test Example 6: Pharmacokinetics test in mice A compound of the present disclosure was administered intravenously to 7-week-old female BALB / c (BALB / cAnN CrlCrlj) mice in a 50% PEG solution (0.01 mol / L HCl) at a dose of 1 mg / kg or orally in a 0.5% aqueous methylcellulose solution at a dose of 10 mg / kg, and blood was collected at the following times: 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

[0359] The collected blood was centrifuged at 3000 rpm for 10 minutes in a refrigerated centrifuge set at 4°C, and the resulting plasma was measured by LC-MS. A calibration curve was created from the peak area of ​​the test substance in MS divided by the peak area of ​​the internal standard (peak ratio) and the concentration of the plasma calibration curve sample. The concentration in each sample was calculated from the peak ratio and the calibration curve.

[0360] The test results for Examples 2, 7, 19, 44, 46 and 51 are shown in Table 22.

[0361] The results of this test confirmed that the compounds of the present disclosure have excellent pharmacokinetics and are useful in vivo. In particular, Examples 44, 46, and 51 showed excellent oral absorbability, enabling the compounds to exert anticancer effects by oral administration. [Table 22]

[0362] Test Example 7: Intratumor and plasma pharmacokinetics test using G-401 xenograft model mice Four- to six-week-old female BALB / cAnNCrj-nu / nu mice (CAnN.Cg-Foxn1 <nu>5x10 G-401 cells (ATCC) were intradermally injected into the skin. 5 The tumor volume was calculated using the following formula, using the short and long diameters of the tumor measured with an electronic caliper (Mitutoyo). Tumor volume [mm 3 ] = 0.5 × minor axis [mm] × (major axis [mm]) 2 Tumor volume 100mm 3 from 200mm 3 The test compound was orally administered in a 0.5% methylcellulose solution (dosage: 30 or 10 mg / kg) to the mice that reached the age of 18. The test compound was administered twice a day for a total of three times, and blood and tumor samples were collected four hours after the final administration. The collected blood was centrifuged at 3000 rpm for 10 minutes using a refrigerated centrifuge set at 4°C to obtain a plasma fraction. Methanol was added to the collected tumor in an amount four times the tumor weight, and the tumor was then thawed. Tumor homogenates were prepared by crushing the samples at 4200 rpm for 20 seconds under cooling using a hose-type homogenizer. The resulting plasma and tumor homogenates were analyzed by LC-MS. A calibration curve was created from the peak area of ​​the test substance divided by the peak area of ​​the internal standard (peak ratio) and the concentration of the plasma or tumor calibration curve sample. The concentration of each sample was calculated from the peak ratio and the calibration curve.

[0363] The test results for Example 46 and Comparative Example 1 are shown in Table 23.

[0364] In Comparative Example 1, both the plasma concentration and intratumor concentration increased with an increase in the dose from 10 mg / kg to 30 mg / kg, and the tumor penetration (ratio of plasma concentration to tumor concentration) was almost equivalent at 10 mg / kg and 30 mg / kg. On the other hand, Example 46 showed the unexpected effect of showing a higher tumor penetration rate at 30 mg / kg than at 10 mg / kg, while the plasma concentration decreased as the dose increased from 10 mg / kg to 30 mg / kg.

[0365] The test results revealed that Example 46 exhibited heterogeneous and exceptionally significant tumor migration, which could exert a strong anticancer effect, compared to Comparative Example 1. [Table 23]

[0366] Test Example 8: Drug efficacy evaluation test by oral administration using G-401 xenograft model mice Four to seven-week-old BALB / cAnNCrj-nu / nu mice (CAnN.Cg-Foxn1 <nu>5x10 G-401 cells (ATCC) were intradermally injected into the skin. 5 The tumors were transplanted at 1000 x 1000 cells / mouse. After confirming the engraftment of G-401 cells 20-40 days after transplantation, the test compound suspended in a solvent such as 0.5% methylcellulose solution was orally administered twice daily at doses of 1-100 mg / kg. The tumor volume was measured over time from the start of administration, and the effect of the test compound on tumor volume reduction was evaluated. The tumor volume was calculated using the following formula, using the minor and major diameters of the tumor measured with an electronic caliper (Mitutoyo). Tumor volume [mm 3 ] = 0.5 × minor axis [mm] × (major axis [mm]) 2

[0367] A control group administered with only a solvent such as 0.5% methylcellulose solution was compared with a test compound administered group, and T / C was calculated using the following formula to evaluate the antitumor effect. T / C (%) = (tumor volume at the end of administration in the test compound administration group - tumor volume at the start of administration in the test compound administration group) / (tumor volume at the end of administration in the control administration group - tumor volume at the start of administration in the control administration group) × 100 [Table 24]

[0368] For Example 46, the test results are shown in Table 24. The results of this test showed that Example 46 exhibited a strong antitumor effect in a G-401 xenograft model, which is a cell line derived from malignant rhabdoid tumor.

[0369] The results of Test Examples 1 to 8 show that the compounds disclosed herein exhibited potent HAT inhibitory activity (Test Example 1) and potent cancer cell proliferation inhibitory effects (Test Example 2). Furthermore, the compounds disclosed herein exhibited high solution stability (Test Example 3), excellent solubility (Test Example 4), high membrane permeability (Test Example 5), favorable pharmacokinetics (Test Example 6), and exceptionally significant and heterogeneous tumor migration (Test Example 7), as well as exceptional antitumor effects (Test Example 8).

[0370] The present inventors have newly discovered the problem that the compounds of Comparative Examples 1 and 2 have low solubility and are unstable in solution, making intravenous administration difficult. Generally, structural transformation to increase solubility reduces lipid solubility and impairs membrane permeability. However, among the compounds of the present invention, the compounds represented by formulas (2) to (7) in particular have a unique effect of combining excellent solubility (Test Example 4) and high membrane permeability (Test Example 5), and are excellent CBP / P300 inhibitors that can be administered orally and intravenously.

[0371] Among the compounds of the present invention, Example 46, which is included in formula (2) and formula (3), exhibited potent HAT inhibitory activity (Test Example 1) and potent cancer cell proliferation inhibitory effect (Test Example 2). In addition, Example 46 exhibited exceptionally remarkable effects, exhibiting superior solution stability (Test Example 3) compared to Comparative Examples 1 and 2. Generally, structural transformation to increase solubility reduces lipophilicity and impairs membrane permeability. However, Example 46 exhibited better solubility than Comparative Examples 1 and 2 (Test Example 4) and membrane permeability equivalent to Comparative Examples 1 and 2 (Test Example 5), demonstrating heterogeneous effects. Furthermore, Example 46 exhibited excellent pharmacokinetics (Test Example 6), possessed exceptionally remarkable and heterogeneous effects, exhibiting higher tumor penetration compared to Comparative Example 1 (Test Example 7), and exhibited exceptional antitumor effect (Test Example 8). Therefore, Example 46 is a CBP / P300 inhibitor with a profile suitable for oral and intravenous administration. [Industrial Applicability]

[0372] The compounds of the present disclosure and pharmaceutically acceptable salts thereof are useful as therapeutic or preventive agents for pathologies involving CBP / P300 by potently inhibiting CBP / P300.< / nu> < / nu>

Claims

【Request 1】 【Chemical 1】 [In the formula, A is CR ６ａ R ６ｂ , C═O, C═CH ２ , or S(=O) ２ represents B is represented by the following formula (B-1): 【Chemistry 2】 [wherein * represents the bonding position to the nitrogen atom of 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 is -O-, -N(R ７ａ )-, an optionally substituted 6- to 10-membered divalent aromatic ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, or an optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group; R １ is an optionally substituted C １－６ Alkyl or optionally substituted C ３－１０ represents an alicyclic group, R ２ａ and R ２ｂ each independently represents an optionally substituted C １－６ represents alkyl, where R ２ａ and R ２ｂ together with the carbon atom to which they are attached, may be substituted C ３－６ may form a cycloalkylene or an optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group; R ３ is an optionally substituted C ６－１０ Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted C ３－１０ represents an alicyclic group or an optionally substituted 4- to 10-membered non-aryl heterocyclic group, R ４ represents a single bond, optionally substituted C １－６ Alkylene, optionally substituted C ３－１０ represents a cycloalkylene or an optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group; R ５ represents a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, an optionally substituted C １－６ Alkyl, optionally substituted C １－６ Alkenyl, optionally substituted C １－６ Alkynyl, optionally substituted C １－３ Alkoxy, —NR ７ｂ R ７ｃ , -SO ２ R ７ｄ , -CONR ７ｅ R ７ｆ , optionally substituted C ３－１０ an alicyclic group, or an optionally substituted 4- to 10-membered non-aryl heterocyclic group, an optionally substituted C ６－１０ aryl, optionally substituted 5- to 10-membered heteroaryl, R ６ａ and R ６ｂ are each independently a hydrogen atom, a fluorine atom, or an optionally substituted C １－６ Alkyl or optionally substituted C １－３ represents alkoxy, , R ６ａ and R ６ｂ together with the carbon atom to which they are attached, may be substituted C ３－６ may form a cycloalkylene or an optionally substituted 4- to 6-membered divalent non-aryl heterocycle; R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ are each independently a hydrogen atom or an optionally substituted C １－６ represents alkyl] or a pharmaceutically acceptable salt thereof.

2. R １ , R ２ａ , R ２ｂ , R ３ , R ４ , R ５ , R ６ａ , R ６ｂ , R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ , R ８ , R ９ａ , R ９ｂ , an optionally substituted 6- to 10-membered aromatic hydrocarbon ring, an optionally substituted 5- to 10-membered aromatic heterocyclic ring, an optionally substituted 6- to 10-membered divalent aromatic hydrocarbon ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, an optionally substituted C ６－１０ Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C １－６ Alkyl, optionally substituted C １－６ Alkenyl, optionally substituted C １－６ Alkynyl, optionally substituted C ３－１０ Alicyclic group, optionally substituted C ３－６ Cycloalkylene, optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, optionally substituted C １－６ Alkylene, optionally substituted C ３－１０ Cycloalkylene, optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, optionally substituted C １－３ Each alkoxy is independently (1) a halogen atom, (2) a hydroxyl group, (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, (8) C １－６ Alkoxy, (9) C １－６ Alkylthio (10) C ３－１０ Alicyclic groups, (11) a 3- to 10-membered non-aryl heterocyclic group, (12) carboxyl, (13)-COR １０ 、 (14)-CO ２ R １０ 、 (15) - COCOA １１ R １２ 、 (16)-NR １１ R １２ 、 (17)-NR １３ COR １０ 、 (18)-NR １３ CO ２ R １０ 、 (19)-NR １３ SO ２ R １０ 、 (20)-NR １３ CONR １１ R １２ 、 (21)-NR １３ SO ２ NR １１ R １２ 、 (22)-SO ２ R １０ 、 (23)-SO ２ NR １１ R １２ 、 (24)-OCOR １０ 、 (25)-OCO ２ R １０ 、 (26)-OCONR １１ R １２ 、 (27) sulfonic acid, (28) phosphoric acid, (29) cyano, and (30) Nitro and optionally substituted with 1 to 5 identical or different substituents selected from the group consisting of: Here, the (3) C ６－１０ (4) 5- to 12-membered heteroaryl; (5) C １－６ alkyl, (6) C ２－６ alkenyl, (7) C ２－６ alkynyl, (8) C １－６ Alkoxy, (9) C １－６ Alkylthio, (10)C ３－１０ The groups shown in (11) alicyclic group and (12) 3- to 10-membered non-aryl heterocyclic group are (a) a halogen atom, (b) a hydroxyl group, (c) C ６－１０ aryl, (d) 5- to 12-membered heteroaryl; (e) C １－６ Alkyl, (f) C ２－６ alkenyl, (g) C ２－６ Alkynyl, (h) C １－６ Alkoxy, (i) C ３－１０ Alicyclic groups, (j) a 3- to 10-membered non-aryl heterocyclic group, (k) carboxyl, (l)-COR １０ 、 (m)-CO ２ R １０ 、 (n)-CONR １１ R １２ 、 (o)-NR １１ R １２ 、 (p)-NR １３ COR １０ 、 (q)-NR １３ SO ２ R １０ 、 (r)-SO ２ R １０ 、 (s)-SO ２ NR １１ R １２ 、 (t) sulfonic acid, (u) phosphoric acid, (v) cyano, and (w) Nitro and optionally substituted with 1 to 5 identical or different substituents selected from the group consisting of: R １０ However, if there are multiple, each independently, C １－６ is alkyl, R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, and R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle; R １３ is a hydrogen atom or C １－６ is alkyl, 2. The compound of claim 1, or a pharmaceutically acceptable salt thereof.

3. R １ , R ２ａ , R ２ｂ , R ３ , R ４ , R ５ , R ６ａ , R ６ｂ , R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ , R ８ , R ９ａ , R ９ｂ , an optionally substituted 6- to 10-membered aromatic hydrocarbon ring, an optionally substituted 5- to 10-membered aromatic heterocyclic ring, an optionally substituted 6- to 10-membered divalent aromatic hydrocarbon ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, an optionally substituted C ６－１０ Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C １－６ Alkyl, optionally substituted C １－６ Alkenyl, optionally substituted C １－６ Alkynyl, optionally substituted C ３－１０ Alicyclic group, optionally substituted C ３－６ Cycloalkylene, optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, optionally substituted C １－６ Alkylene, optionally substituted C ３－１０ Cycloalkylene, optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, optionally substituted C １－３ Each alkoxy is independently (1) a halogen atom, (2) a hydroxyl group, (3) C ６－１０ aryl, (4) 5- to 12-membered heteroaryl, (5) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl, (6) C ２－６ alkenyl, (7) C ２－６ Alkynyl, (8) C １－６ Alkoxy, (9) C ３－１０ Alicyclic groups, (10) a 3- to 10-membered non-aryl heterocyclic group, (11) carboxyl, (12)-COR １０ 、 (13)-CO ２ R １０ 、 (14) - -CNR １１ R １２ 、 (15)-NR １１ R １２ 、 (16)-SO ２ R １０ 、 (17)-SO ２ NR １１ R １２ 、 (18) sulfonic acids, (19) phosphoric acid, (20) cyano, and (21) Nitro and optionally substituted with 1 to 5 identical or different substituents selected from the group consisting of: R １０ However, if there are multiple, each independently, C １－６ is alkyl, R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, and R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle; The compound according to any one of claims 1 to 2, or a pharmaceutically acceptable salt thereof.

4. R １ , R ２ａ , R ２ｂ , R ３ , R ４ , R ５ , R ６ａ , R ６ｂ , R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ , R ８ , R ９ａ , R ９ｂ , an optionally substituted 6- to 10-membered aromatic hydrocarbon ring, an optionally substituted 5- to 10-membered aromatic heterocyclic ring, an optionally substituted 6- to 10-membered divalent aromatic hydrocarbon ring group, an optionally substituted 5- to 10-membered divalent aromatic heterocyclic group, an optionally substituted C ６－１０ Aryl, optionally substituted 5- to 10-membered heteroaryl, optionally substituted 4- to 10-membered non-aryl heterocyclic group, optionally substituted C １－６ Alkyl, optionally substituted C １－６ Alkenyl, optionally substituted C １－６ Alkynyl, optionally substituted C ３－１０ Alicyclic group, optionally substituted C ３－６ Cycloalkylene, optionally substituted 4- to 6-membered divalent non-aryl heterocyclic group, optionally substituted C １－６ Alkylene, optionally substituted C ３－１０ Cycloalkylene, optionally substituted 4- to 10-membered divalent non-aryl heterocyclic group, optionally substituted C １－３ Each alkoxy is independently (1) a halogen atom, (2) a hydroxyl group, (3) phenyl, (4) 5- to 6-membered heteroaryl, (5) C optionally substituted with 1 to 3 halogen atoms １－６ Alkyl, (6) C １－６ Alkoxy, (7) C ３－７ Alicyclic groups, (8) a 3- to 7-membered non-aryl heterocyclic group, (9)-COR １０ 、 (10)-CO ２ R １０ 、 (11) - COCOA １１ R １２ 、 (12)-NR １１ R １２ 、 (13)-SO ２ R １０ 、 (14) -SO ２ NR １１ R １２ , and (15) Cyano and optionally substituted with 1 to 5 identical or different substituents selected from the group consisting of: R １０ However, if there are multiple, each independently, C １－６ is alkyl, R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, and R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle; The compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof.

5. R ６ａ and R ６ｂ are each independently a fluorine atom or a methyl group; The compound according to any one of claims 1 to 4 or a pharmaceutically acceptable salt thereof.

6. R ６ａ and R ６ｂ is a fluorine atom, The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof.

7. A is CF ２ , C(F)CH ３ or C=O; The compound according to any one of claims 1 to 6 or a pharmaceutically acceptable salt thereof.

8. A is CF ２ or C=O; The compound according to any one of claims 1 to 7 or a pharmaceutically acceptable salt thereof.

9. B is represented by the following formula (B-2), (B-3), or (B-4): 【Chemistry 3】 [wherein * represents the bonding position to the nitrogen atom of the hydantoin ring, a represents 0, 1, or 2; b represents 1 or 2; R ８ represents a hydrogen atom or an optionally substituted C １－６ represents alkyl, R ９ａ and R ９ｂ are each independently a hydrogen atom, a halogen atom, or an optionally substituted C １－６ represents alkyl] The compound according to any one of claims 1 to 8 or a pharmaceutically acceptable salt thereof.

10. R １ C optionally substituted with 1 to 3 fluorines １－３ is alkyl, The compound according to any one of claims 1 to 9 or a pharmaceutically acceptable salt thereof.

11. R １ But CF ３ That is, The compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof.

12. R ３ But C ６－１０ Aryl (the aryl is a halogen atom and C １－６ 12. The compound according to any one of claims 1 to 11, or a pharmaceutically acceptable salt thereof, wherein R is 1 to 3, and R is 2 to 3, and R is 3 ...

13. R ３ is 4-fluorophenyl; The compound according to any one of claims 1 to 12, or a pharmaceutically acceptable salt thereof.

14. Ring Q is a 6- to 10-membered aromatic hydrocarbon ring (the aromatic hydrocarbon ring is not substituted by a halogen atom or a C １－６ alkyl, each of which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of The compound according to any one of claims 1 to 13, or a pharmaceutically acceptable salt thereof.

15. Ring Q is benzene. The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt thereof.

16. a is 1 or 2; 16. The compound according to any one of claims 1 to 15, or a pharmaceutically acceptable salt thereof.

17. a is 1, 17. The compound according to any one of claims 1 to 16, or a pharmaceutically acceptable salt thereof.

18. b is 1; 18. The compound according to any one of claims 1 to 17, or a pharmaceutically acceptable salt thereof.

19. Formula (1) is changed to the following formula (2): 【Chemistry 4】 [In the formula, A is CF ２ or C═O, Z is -O-, a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ 1 to 3 identical or different substituents selected from the group consisting of (optionally substituted with) or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and --NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ４ teeth, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), C ３－１０ Cycloalkylene (the cycloalkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ５ teeth, hydrogen atoms, halogen atoms, hydroxyl groups, Cyano, -NR ７ｂ R ７ｃ 、 -SO ２ R ７ｄ 、 - -CNR ７ｅ R ７ｆ 、 C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkenyl (the alkenyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkynyl (the alkynyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkoxy (the alkoxy is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ３－１０ an alicyclic group (the alicyclic group is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ６－１０ Aryl (the aryl is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5-10 membered heteroaryl (the heteroaryl is not limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ are each independently a hydrogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. That is, 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

20. A is CF ２ That is, 20. The compound according to any one of claims 1 to 19, or a pharmaceutically acceptable salt thereof.

21. Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

21. The compound according to any one of claims 1 to 20, or a pharmaceutically acceptable salt thereof.

22. Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

22. The compound according to any one of claims 1 to 21, or a pharmaceutically acceptable salt thereof.

23. R ４ but, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

23. The compound according to any one of claims 1 to 22, or a pharmaceutically acceptable salt thereof.

24. R ５ but, hydrogen atoms, -NR ７ｂ R ７ｃ 、 C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkoxy (the alkoxy is a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

24. The compound according to any one of claims 1 to 23, or a pharmaceutically acceptable salt thereof.

25. Formula (1) is changed to the following formula (3): 【Chemistry 5】 [In the formula, R ４ teeth, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ５ teeth, hydrogen atoms, -NR ７ｂ R ７ｃ 、 C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkoxy (the alkoxy is a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ７ｂ , R ７ｃ are each independently a hydrogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

26. R ４ but, a 4- to 10-membered divalent non-aryl heterocyclic group; Item 26. The compound according to any one of Items 1 to 25, or a pharmaceutically acceptable salt thereof.

27. R ４ but, a 4- to 6-membered divalent non-aryl heterocyclic group; 27. The compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof.

28. R ４ but, azetidinylene, 28. The compound according to any one of claims 1 to 27, or a pharmaceutically acceptable salt thereof.

29. R ５ but, C １－６ alkyl, or 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not substituted by a halogen atom or a C １－６ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of alkyl and 29. The compound according to any one of claims 1 to 28, or a pharmaceutically acceptable salt thereof.

30. R ５ but, C １－３ alkyl, or 4- to 6-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not substituted by a halogen atom or a C １－６ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of alkyl and 30. The compound according to any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof.

31. R ５ but, is methyl, 31. The compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof.

32. R ５ but, oxetanyl, 31. The compound according to any one of claims 1 to 30, or a pharmaceutically acceptable salt thereof.

33. Formula (1) is changed to the following formula (4): 【Chemistry 6】 [In the formula, A is CF ２ or C═O, Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and --NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ４ teeth, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), C ３－１０ Cycloalkylene (the cycloalkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ５ teeth, hydrogen atoms, halogen atoms, hydroxyl groups, Cyano, -NR ７ｂ R ７ｃ 、 -SO ２ R ７ｄ 、 - -CNR ７ｅ R ７ｆ 、 C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkenyl (the alkenyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkynyl (the alkynyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－３ Alkoxy (the alkoxy is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ３－１０ an alicyclic group (the alicyclic group is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ６－１０ Aryl (the aryl is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5-10 membered heteroaryl (the heteroaryl is not limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ are each independently a hydrogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R ８ teeth, a hydrogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. That is, 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

34. A is CF ２ That is, 34. The compound according to any one of claims 1 to 33, or a pharmaceutically acceptable salt thereof.

35. Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

35. The compound according to any one of claims 1 to 34, or a pharmaceutically acceptable salt thereof.

36. Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

36. The compound according to any one of claims 1 to 35, or a pharmaceutically acceptable salt thereof.

37. R ４ but, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), or C ３－１０ Cycloalkylene (the cycloalkylene is a halogen atom and C １－６ alkyl, each of which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 37. The compound according to any one of claims 1 to 36, or a pharmaceutically acceptable salt thereof.

38. R ５ but, hydrogen atoms, Cyano, C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

38. The compound according to any one of claims 1 to 37, or a pharmaceutically acceptable salt thereof.

39. R ８ but, C １－６ is alkyl, 39. The compound according to any one of claims 1 to 38, or a pharmaceutically acceptable salt thereof.

40. Formula (1) is changed to the following formula (5): 【Chemistry 7】 [In the formula, R ４ teeth, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ５ teeth, hydrogen atoms, Cyano, C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of -SO ２ R ７ｄ 、 -CONR ７ｅ R ７ｆ , or 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ７ｄ , R ７ｅ , R ７ｆ are each independently a hydrogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

41. R ４ but, a single bond, or C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl, each of which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 41. The compound according to any one of claims 1 to 40, or a pharmaceutically acceptable salt thereof.

42. R ４ is a single bond, 42. The compound according to any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof.

43. R ４ But C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl, each of which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 42. The compound according to any one of claims 1 to 41, or a pharmaceutically acceptable salt thereof.

44. R ５ but, C １－６ alkyl, or It is cyano, 44. The compound according to any one of claims 1 to 43, or a pharmaceutically acceptable salt thereof.

45. R ５ but, is a methyl group, 45. The compound according to any one of claims 1 to 44, or a pharmaceutically acceptable salt thereof.

46. R ５ but, It is cyano, 45. The compound according to any one of claims 1 to 44, or a pharmaceutically acceptable salt thereof.

47. Formula (1) is changed to the following formula (6): 【Chemistry 8】 [In the formula, A is CF ２ or C═O, Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and --NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ４ teeth, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ A group consisting of alkyl and optionally substituted with 1 to 3 identical or different substituents selected from C ３－１０ Cycloalkylene (the cycloalkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ５ teeth, hydrogen atoms, halogen atoms, hydroxyl groups, Cyano, -NR ７ｂ R ７ｃ 、 -SO ２ R ７ｄ 、 - -CNR ７ｅ R ７ｆ 、 C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkenyl (the alkenyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－６ Alkynyl (the alkynyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C １－３ Alkoxy (the alkoxy is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ３－１０ an alicyclic group (the alicyclic group is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ６－１０ Aryl (the aryl is a halogen atom, C １－６ Alkyl and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of 5-10 membered heteroaryl (the heteroaryl is not limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ７ａ , R ７ｂ , R ７ｃ , R ７ｄ , R ７ｅ , R ７ｆ are each independently a hydrogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R ９ａ and R ９ｂ are each independently hydrogen atoms, a halogen atom, or C １－６ Alkyl (the alkyl is a halogen atom and C １－６ alkyl), which may be substituted with 1 to 3 identical or different substituents selected from the group consisting of R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, R １１ or R １２ If there are multiple １１ or R １２ Each of the following can be the same or different. Preferably, R bonded to the same nitrogen atom １１ and R １２ Both are C １－６ When they are alkyl, they may be joined together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle. ], 2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

48. A is CF ２ That is, 48. The compound according to any one of claims 1 to 47, or a pharmaceutically acceptable salt thereof.

49. Z is a 6- to 10-membered divalent aromatic ring group (the divalent aromatic ring group is not a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 5- to 10-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

49. The compound according to any one of claims 1 to 48, or a pharmaceutically acceptable salt thereof.

50. Z is a 5-membered divalent aromatic heterocyclic group (the divalent aromatic heterocyclic group is not limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

50. The compound according to any one of claims 1 to 49, or a pharmaceutically acceptable salt thereof.

51. R ４ but, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the divalent non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

51. The compound according to any one of claims 1 to 50, or a pharmaceutically acceptable salt thereof.

52. R ５ but, hydrogen atoms, Cyano, -NR ７ｂ R ７ｃ 、 C １－６ Alkyl (the alkyl is a halogen atom, C １－６ Alkyl, hydroxyl group and -NR １１ R １２ may be substituted with 1 to 3 identical or different substituents selected from the group consisting of C ３－１０ an alicyclic group (the alicyclic group is a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of: 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of:

52. The compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt thereof.

53. R ９ａ and R ９ｂ but, is a fluorine atom, 53. The compound according to any one of claims 1 to 52, or a pharmaceutically acceptable salt thereof.

54. Formula (1) is changed to the following formula (7): 【Chemistry 9】 [In the formula, R ４ teeth, single bond, C １－６ Alkylene (the alkylene is a halogen atom and C １－６ alkyl), or a 4- to 10-membered divalent non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to a halogen atom, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R ５ teeth, hydrogen atoms, Cyano, C １－６ Alkyl, C １－６ alkenyl, C １－６ alkynyl, or 4- to 10-membered non-aryl heterocyclic group (the non-aryl heterocyclic group is not particularly limited to halogen atoms, C １－６ Alkyl and -NR １１ R １２ and optionally substituted with 1 to 3 identical or different substituents selected from the group consisting of R １１ and R １２ are each independently a hydrogen atom or C １－６ represents alkyl, R １１ or R １２ If there are multiple １１ or R １２ may be the same or different, and R １１ and R １２ Both are C １－６ When they are alkyl, they may be taken together with the nitrogen atom to which they are attached to form a 3- to 8-membered nitrogen-containing non-aryl heterocycle.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof.

55. R ４ but, a 4- to 10-membered divalent non-aryl heterocyclic group; 55. The compound according to any one of claims 1 to 54, or a pharmaceutically acceptable salt thereof.

56. R ４ but, a 4- to 6-membered divalent non-aryl heterocyclic group; 56. The compound according to any one of claims 1 to 55, or a pharmaceutically acceptable salt thereof.

57. R ４ but, azetidinylene, 57. The compound according to any one of claims 1 to 56, or a pharmaceutically acceptable salt thereof.

58. R ５ but, C １－６ alkyl, or a 4- to 10-membered non-aryl heterocyclic group; 58. The compound according to any one of claims 1 to 57, or a pharmaceutically acceptable salt thereof.

59. R ５ but, C １－３ alkyl, or a 4- to 6-membered non-aryl heterocyclic group; 59. The compound according to any one of claims 1 to 58, or a pharmaceutically acceptable salt thereof.

60. R ５ but, is methyl, 60. The compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof.

61. R ５ but, oxetanyl, 60. The compound according to any one of claims 1 to 59, or a pharmaceutically acceptable salt thereof.

62. 2. The compound of claim 1, selected from the following compounds, or a pharmaceutically acceptable salt thereof: N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[2-(azetidin-1-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclobutyl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-2-[(1'S)-5'-{1-[2-(dimethylamino)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-{(1'S)-5'-[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-(1,1,1-trifluoro-2-methylpropan-2-yl)acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-4-(trifluoromethyl)piperidin-4-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-(6-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-1,1,2',5'-tetraoxo-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl)-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-2-{6-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-1,1,2',5'-tetraoxo-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl}-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-{(1'S)-5'-[1-(1-cyanocyclopropyl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide, 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-(1-methyl-1H-pyrazol-4-yl)-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[6-(1-methyl-1H-pyrazol-4-yl)-1,1,2',5'-tetraoxo-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide, 2-{(1'S)-5'-[1-(1-cyclobutylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[2-(3-methoxyazetidin-1-yl)ethyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[(2R)-2-(dimethylamino)propyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]-2-[(1'S)-2,3',5-trioxo-5'-{1-[1-(propyl-2-en-1-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide, 2-[(1'S)-5'-{1-[1-(2,2-difluoroethyl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[1-(3,3-difluorocyclobutyl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[3-(cyanomethyl)-1-methylazetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[(2S)-2-(dimethylamino)propyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-{(1'S)-5'-[1-(1-cyclopropylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[(3-fluoro-1-methylazetidin-3-yl)methyl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide, N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]-2-[(1'S)-5'-{1-[1-(oxetan-3-yl)piperidin-4-yl]-1H-pyrazol-4-yl}-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]acetamide, 2-{(1'S)-5'-[1-(1-cyclobutylazetidin-3-yl)-1H-pyrazol-4-yl]-2,3',5-trioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide, N-[(4-fluorophenyl)methyl]-2-(1,1,2',5'-tetraoxo-6-{1-[1-(propyl-2-yn-1-yl)azetidin-3-yl]-1H-pyra {1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4′-imidazolidine]-1′-yl)-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-2-(1,1,2',5'-tetraoxo-6-{1-[1-(propyl-2-en-1-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-1,2-dihydro-1λ-6-spiro[[1]benzothiophene-3,4'-imidazolidine]-1'-yl)-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-2,5-dioxo-5'-(pyridin-3-yl)-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-2,5-dioxo-5'-(pyridin-4-yl)-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-2,5-dioxo-5'-(pyrimidin-5-yl)-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-{(1'S)-3',3'-difluoro-2,5-dioxo-5'-[6-(pyrrolidin-1-yl)pyridin-3-yl]-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylpiperidin-4-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetami Do, 2-{(1'S)-3',3'-difluoro-5'-[6-(4-methylpiperazin-1-yl)pyridin-3-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-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, 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-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, 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-{1-[(3-fluoro-1-methylazetidin-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-5'-{1-[(2R)-2-(dimethylamino)propyl]-1H-pyrazol-4-yl}-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-{1-[(3-fluoro-1-methylazetidin-3-yl)methyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide, 2-{(1'S)-5'-[1-(azetidin-3-yl)-1H-pyrazol-4-yl] -3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-{(1'S)-5'-[2-(dimethylamino)ethoxy]-3',3'-difluoro-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-(3-methoxyazetidin-1-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-(3-methoxypiperidin-1-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-3'-methylidene-5'-(1-methyl-1H-pyrazol-4-yl)-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-methyl-3-(trifluoromethyl)azetidin-3-yl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(1'S)-3'-methylidene-5'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, N-[(4-fluorophenyl)methyl]-2-[(3'S)-6'-{1-[2-(morpholin-4-yl)ethyl]-1H-pyrazol-4-yl}-2",5''-dioxo-2'H-dispiro[cyclopropane-1,1'-indene-3',4''-imidazolidine]-1''-yl]-N-[1-(trifluoromethyl)cyclopropyl]acetamide, 2-[(1'S,3'R)-3'-fluoro-3'-methyl-5'-(1-methyl-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.

63. 2. The compound of claim 1, selected from the following compounds, or a pharmaceutically acceptable salt thereof: 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-{(1'S)-3',3'-difluoro-5'-[1-(1-methylazetidin-3-yl)-1H-pyrazol-4-yl]-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl}-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide, 2-[(1'S)-3',3'-difluoro-5'-(1-methyl-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, 2-{(1'S)-5'-[1-(2-cyanopropan-2-yl)-1H-pyrazol-4-yl]-3',3'-difluoro-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, 2-[(1'S)-3',3'-difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[(4-fluorophenyl)methyl]-N-[3-(trifluoromethyl)oxetan-3-yl]acetamide, 2-[(1'S)-3',3'-Difluoro-5'-{1-[1-(oxetan-3-yl)azetidin-3-yl]-1H-pyrazol-4-yl}-2,5-dioxo-2',3'-dihydrospiro[imidazolidine-4,1'-inden]-1-yl]-N-[3,3-difluoro-1-(trifluoromethyl)cyclobutyl]-N-[(4-fluorophenyl)methyl]acetamide.

64. A pharmaceutical comprising the compound according to any one of claims 1 to 63 or a pharmaceutically acceptable salt thereof as an active ingredient.

65. 64. A pharmaceutical composition comprising the compound according to any one of claims 1 to 63 or a pharmaceutically acceptable salt thereof.

66. A therapeutic and / or preventive agent for cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease, comprising the compound according to any one of claims 1 to 63 or a pharmaceutically acceptable salt thereof as an active ingredient.

67. 64. A cancer treatment and / or prevention agent comprising the compound according to any one of claims 1 to 63 or a pharmaceutically acceptable salt thereof as an active ingredient.

68. The therapeutic and / or prophylactic agent according to claim 66 or 67, wherein the cancer is at least one type of cancer selected from the group consisting of SMARC-deficient cancer, SS18-SSX fusion cancer, and ARID-deficient cancer.

69. The cancer is selected from the group consisting of malignant rhabdoid tumor, epithelioid sarcoma, atypical teratoid / rhabdoid tumor, schwannoma, chordotomy meningioma, neuroepithelial tumor, glioneuronal tumor, craniopharyngioma, glioblastoma, chordoma, myoepithelial tumor, extraskeletal myxoid chondrosarcoma, synovial sarcoma, ossifying fibromyxoid tumor, basaloid carcinoma of the paranasal sinus, esophageal cancer, papillary thyroid cancer, follicular thyroid cancer, gastrointestinal stromal tumor, pancreatic undifferentiated rhabdoid tumor, gastrointestinal rhabdoid tumor, renal medullary cancer, endometrial cancer, myoepithelioma-like tumor of the female vulva, colorectal cancer, mesothelioma, lung adenocarcinoma, large cell lung carcinoma, and pulmonary neuroendocrine tumor. The therapeutic and / or prophylactic agent according to any one of claims 66 to 68, wherein the cancer is at least one type selected from the group consisting of secretory tumor, gastroesophageal junction cancer, gastric cancer, bladder cancer, lung squamous cell carcinoma, pancreatic cancer, medulloblastoma, renal clear cell carcinoma, liver cancer, lung pleomorphic carcinoma, breast sarcoma, ovarian small cell carcinoma, primary gallbladder tumor, uterine sarcoma, ovarian granulosa tumor, adrenocortical carcinoma, small cell lung cancer, ovarian cancer, endometrial cancer, neuroblastoma, ovarian mucinous tumor, nasal and paranasal cancer, thoracic sarcoma, biliary tract cancer, neuroblastoma, melanoma, breast cancer, and Ewing's sarcoma.

70. A method for treating or preventing cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease, comprising administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of a compound according to any one of claims 1 to 63 or a pharmaceutically acceptable salt thereof.

71. Use of the compound according to any one of claims 1 to 63 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment or prevention of cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease.

72. 64. The compound according to any one of claims 1 to 63, or a pharmaceutically acceptable salt thereof, for use in the treatment or prevention of cancer, non-alcoholic fatty liver disease (NAFLD), acute liver damage, heart disease, or metabolic disease.

73. The compound according to any one of claims 1 to 63, or a pharmaceutically acceptable salt thereof, for treating cancer in combination with a concomitant drug or a pharmaceutically acceptable salt thereof, wherein the concomitant drug is at least one or more selected from the group consisting of drugs such as hormone therapy agents, chemotherapeutic agents, immunotherapy agents, and agents that inhibit the action of cell growth factors and their receptors, or the like.

74. 64. The pharmaceutical composition according to claim 1, wherein the compound according to claim 1 is a medicament for treating a rheumatoid arthritis, ...

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