IP Library › Granted Patent US 12,410,212
Granted Patent B2
US 12,410,212 · App. 18/829,566 · Granted Sep 9, 2025

Cyclic compound having selective KRAS inhibitory effect on HRAS and NRAS

Inventors: Hatsuo Kawada (Kamakura, JP); Koji Takano (Kamakura, JP); Tomoya Kotake (Gotemba, JP); Mirai Kage (Gotemba, JP); Satoshi Hashimoto (Gotemba, JP); Minoru Tamiya (Kamakura, JP); Yuma Wakamiya (Kamakura, JP); Ryuji Hayashi (Kamakura, JP); Yuya Morita (Kamakura, JP)
Assignee: CHUGAI SEIYAKU KABUSHIKI KAISHA
C07K9/006A61K38/12C07K7/64
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Quick Facts
Patent No.
US 12,410,212
App. No.
18/829,566
Granted
Sep 9, 2025
Kind
B2
Abstract

Cyclic compounds that selectively inhibit KRAS were found. Moreover, cyclic compounds were found to interact with an amino acid residue specific to KRAS.

Claims (24)

1. A compound, which is (1S,4S,10S,13S,17S,20S,26S,28R,32S,38S,42Z)-20-cyclopentyl-28-ethoxy-32-[2-[3-methoxy-4-(trifluoromethyl)phenyl]ethyl]-N,N,2,14,18,21,24,36-octamethyl-10-[(1S)-1-methylpropyl]-3,9,12,15,19,22,25,31,34,37,45-undecaoxo-13-propyl-38-[[4-(trifluoromethyl)phenyl]methyl]spiro[2,8,11,14,18,21,24,30,33,36,39-undecazatetracyclo [37.5.1.0 4,8 .0 26,30 ] pentatetracont-42-ene-23,l′-cyclobutane]-17-carboxamide.

2. A pharmaceutical composition comprising the compound of claim 1 .

3. A method of inhibiting KRAS in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the compound of claim 1 .

4. A method of treating or preventing cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the compound of claim 1 .

5. The method of claim 4 , wherein the cancer is lung cancer.

6. The method of claim 4 , wherein the subject is human.

7. A solvate of (1S,4S,10S,13S,17S,20S,26S,28R,32S,38S,42Z)-20-cyclopentyl-28-ethoxy-32-[2-[3-methoxy-4-(trifluoromethyl)phenyl]ethyl]-N,N,2,14,18,21,24,36-octamethyl-10-[(1S)-1-methylpropyl]-3,9,12,15,19,22,25,31,34,37,45-undecaoxo-13-propyl-38-[[4-(trifluoromethyl)phenyl]methyl]spiro[2,8,11,14,18,21,24,30,33,36,39-undecazatetracyclo [37.5.1.0 4,8 .0 26,30 ] pentatetracont-42-ene-23,1′-cyclobutane]-17-carboxamide.

8. A pharmaceutical composition comprising the solvate of claim 7 .

9. A method of selectively inhibiting KRAS in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the solvate of claim 7 .

10. A method of treating or preventing cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the solvate of claim 7 .

11. The method of claim 10 , wherein the cancer is lung cancer.

12. The method of claim 10 , wherein the subject is human.

13. The solvate according to claim 7 , which is a hydrate.

14. A pharmaceutical composition comprising the solvate of claim 13 .

15. A method of selectively inhibiting KRAS in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the solvate of claim 13 .

16. A method of treating or preventing cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the solvate of claim 13 .

17. The method of claim 16 , wherein the cancer is lung cancer.

18. The method of claim 16 , wherein the subject is human.

19. A salt of (1S,4S,10S,13S,17S,20S,26S,28R,32S,38S,42Z)-20-cyclopentyl-28-ethoxy-32-[2-[3-methoxy-4-(trifluoromethyl)phenyl]ethyl]-N,N,2,14,18,21,24,36-octamethyl-10-[(1S)-1-methylpropyl]-3,9,12,15,19,22,25,31,34,37,45-undecaoxo-13-propyl-38-[[4-(trifluoromethyl)phenyl]methyl]spiro[2,8,11,14,18,21,24,30,33,36,39-undecazatetracyclo [37.5.1.0 4,8 .0 26,30 ] pentatetracont-42-ene-23,1′-cyclobutane]-17-carboxamide, or a solvate thereof.

20. A pharmaceutical composition comprising the salt of claim 19 , or a solvate thereof.

21. A method of inhibiting KRAS in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the salt of claim 19 , or a solvate thereof.

22. A method of treating or preventing cancer in a subject, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of the salt of claim 19 , or a solvate thereof.

23. The method of claim 22 , wherein the cancer is lung cancer.

24. The method of claim 22 , wherein the subject is human.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 11, 2024
From: KAWADA, HATSUO; TAKANO, KOJI; KOTAKE, TOMOYA; KAGE, MIRAI; HASHIMOTO, SATOSHI; TAMIYA, MINORU; WAKAMIYA, YUMA; HAYASHI, RYUJI; MORITA, YUYA
To: CHUGAI SEIYAKU KABUSHIKI KAISHA
Reel/Frame 068552/0717 →
Priority Claims (1)
JP 2022-076449 · May 6, 2022 · national
Continuity (2)
Continuation PCTJP2023017112 · May 2, 2023
Related Publication 20250051394A1 · Feb 13, 2025
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