A BRIDGED PIPERAZINE-SUBSTITUTED HETEROCYCLIC PYRIMIDINE COMPOUND
Patent Information
- Application Number
- RU2025102734
- Authority / Receiving Office
- RU · RU
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2023-07-11
- Publication Date
- 2026-08-31
Claims
1. A compound represented by formula (III-1) or a pharmaceutically acceptable salt thereof, , Where X is selected from CH, C-Rx, N and N + -O - ; preferably X is selected from N and N + -O - ; Rx is selected from F, Cl and Br; R1 is selected from , and at the same time each of independently and optionally substituted with 1, 2, 3, or 4 R a ; R3 is selected from H and D; each R a independently selected from F, Cl, Br, I, OH, NH2, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 2-4 alkenyl, C 2-4 alkynyl, -C 1-3 alkyl cyclopropyl and cyclopropyl, and each of the C 1-3 alkyl, C 1-3 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, cyclopropyl and -C 1-3 alkyl cyclopropyl independently and optionally substituted with 1, 2 or 3 R; each R is independently selected from F, Cl, Br, I, CH2F, CHF2, and CF3.
2. A compound represented by formula (III-1) or a pharmaceutically acceptable salt thereof, , Where X is selected from CH, N and N + -O - ; preferably X is selected from N and N + -O - ; R1 is selected from , and at the same time each of independently and optionally substituted with 1, 2, 3, or 4 R a ; R3 is selected from H and D; each R a independently selected from F, Cl Br, I, OH, NH2, C 1-3 alkyl, C 1-3 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, -C 1-3 alkyl cyclopropyl and cyclopropyl, and each of the C 1-3 alkyl, C 1-3 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, cyclopropyl and -C 1-3 alkyl cyclopropyl independently and optionally substituted with 1, 2 or 3 R; each R is independently selected from F, Cl, Br, I, CH2F, CHF2, and CF3.
3. Compounds represented by formulas (II) and (III-2), or a pharmaceutically acceptable salt thereof, , Where R1 is selected from phenyl, pyridyl and naphthyl, and wherein each of phenyl, pyridyl and naphthyl is independently and optionally substituted with 1, 2, 3 or 4 R a ; R2 is selected from , , and at the same time each of , independently and optionally substituted with 1, 2, or 3 R c ; R3 is selected from H and D; each R a independently selected from F, Cl, Br, I, OH, NH2, C 1-3 alkyl, C 1-3 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, -C 1-3 alkyl cyclopropyl and cyclopropyl, and each of the C 1-3 alkyl, C 1-3 alkoxy, C 2-4 alkenyl, C 2-4 alkynyl, cyclopropyl and -C 1-3 alkyl cyclopropyl independently and optionally substituted with 1, 2 or 3 R; R b selected from H, CN, CH3 and OCH3; each R c independently selected from F, CL, Br, I, CH2F, CHF2, CF3, and CH2CF3; each R is independently selected from F, Cl, Br, I, CH2F, CHF2, and CF3.
4. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein each R a independently selected from F, Cl, OH, NH2, CH3, CCH2CH3, CH(CH3)2, OCH3, OCCH2CH3, OCH(CH3)2, and cyclopropyl, and each of CH3, CH2CH3, CH(CH3)2, OCH3, OCCH2CH3, OCH(CH3)2, and cyclopropyl independently and optionally substituted with I, 2 or 3 R.
5. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 3, wherein each R a independently selected from F, Cl, OH, NH2, CH3, CHF2, CF3, CH2CF3, CH(CH3)CF3, OCH3, OCF3, , .
6. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein R1 is selected from , 7. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein R1 is selected from , and at the same time each of independently and optionally substituted with 1, 2, 3, or 4 R a .
8. A compound or pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein R1 is selected from , 9. A compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-3, wherein R1 is selected from And .
10. The compound or pharmaceutically acceptable salt thereof according to claim 3, wherein R2 is selected from .
11. The compound or pharmaceutically acceptable salt thereof according to claim 3, wherein R2 is selected from , 12. The compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein X is N.
13. A compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein the compound is selected from: . where R1 and R3 are as defined in paragraph 1.
14. A compound or pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein the compound is selected from: where X, R1 and R3 are as defined in paragraph 1.
15. The compound or pharmaceutically acceptable salt thereof according to claim 3, wherein the compound is selected from: where R1 and R3 are as defined in paragraph 3.
16. The compound below or a pharmaceutically acceptable salt thereof, or .
17. A compound or a pharmaceutically acceptable salt thereof according to claim 16, selected from And .
18. The compound or pharmaceutically acceptable salt thereof according to claim 17, wherein the compound is selected from:
19. Use of a compound or a pharmaceutically acceptable salt thereof according to any one of claims 1-18 in the manufacture of a compound for the treatment of solid tumors with a KRAS mutation G12D .