JPWO2020072797A5

JPWO2020072797A5 -

Info

Publication number: JPWO2020072797A5
Application number: JP2021518561A
Authority: JP
Publication date: 2022-11-04
Anticipated expiration: 2039-10-03

Claims

2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1R,3S)-(+)-camforate,
2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1S,3R)-(-)-camphorate ,
2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (R)-(-)-mandelate , and
2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1S)-(+)-camsylate
2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salts selected from the group consisting of :

The 2-{4-[(3S) of claim 1, wherein the 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt is in crystalline form. -piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt.

The 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7 according to claim 2, which is -indazole-7-carboxamide (1R,3S)-(+)-camphorate. - Carboxamide salts.

The crystalline form of the 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1R,3S)-(+)-camphorate was analyzed using Cu K-rays. When measured about 13.4°, about 15.2°, about 16.2°, about 17.5°, about 18.0°, about 20.0°, about 20.4°, about 21.5°. 4. The 2-{4-[( 3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt.

The crystalline form of said 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1R,3S)-(+)-camphorate substantially conforms to FIG. 4. The 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt according to claim 3 characterized by a linear powder diffraction (XRPD) pattern.

The 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7 according to claim 2, which is -indazole-7-carboxamide (1S,3R)-(-)-camphorate. - Carboxamide salts.

The crystalline form of the 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1S,3R)-(−)-camphorate was analyzed using Cu K-rays. When measured at about 11.6°, about 15.1°, about 16.2°, about 17.4°, about 19.9°, about 20.2°, about 20.3°, about 22°. 7. The 2-{4-[( 3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt.

The crystalline form of said 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1S,3R)-(−)-camphorate substantially conforms to FIG. 7. The 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt according to claim 6, characterized by a linear powder diffraction (XRPD) pattern.

The 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide of claim 2, which is (R)-(−)-mandelate. salt.

The crystalline morphology of the 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (R)-(−)-mandelate was measured using Cu K-ray about 8.6°, about 8.7°, about 13.7°, about 16.4°, about 17.4°, about 18.4°, about 18.5°, about 21.5° , about 25.1°, about 27.3°, about 27.6°, about 28.0° and about 28.7° 2-theta. (XRPD) pattern.

X-ray powder wherein the crystalline form of said 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (R)-(-)-mandelate substantially conforms to FIG. A 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt according to claim 9, characterized by a diffraction (XRPD) pattern.

The 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt is 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide according to claim 2, which is -indazole-7-carboxamide (1S)-(+)-camsylate salt.

The crystalline morphology of the 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1S)-(+)-camsylate was measured using Cu K-ray about 11.1°, about 13.5°, about 16.0°, about 16.4°, about 16,7°, about 17.6°, about 20.3°, about 23.7° 13. The 2-{ of claim 12 characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three diffraction angles selected from the group consisting of 2-theta of about 24.3° and about 24.6°. 4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt.

X-ray powder wherein the crystalline form of said 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (1S)-(+)-camsylate substantially conforms to FIG. 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt according to claim 12 characterized by diffraction (XRPD) pattern.

2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide salt according to any one of claims 1 to 14 and at least one pharmaceutically acceptable possible excipients.

16. A pharmaceutical composition according to claim 15, adapted for oral administration.

17. A pharmaceutical composition according to claim 15 or 16 in the manufacture of a medicament for treating cancer, stroke, autoimmune diabetes, neurological disease, inflammatory disease, metabolic disease or cardiovascular disease in a human in need thereof use of things.

18. Use according to claim 17, wherein the medicament is a medicament for treating cancer.

said cancer is associated with mutations in ATM, ATR, BAP1, BARD1, BLM, BRCA1, BRCA2, BR1P1, MRE11A, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, RAD52, RAD54L or XRCC2 or any combination thereof 19. Use according to claim 18.

20. Use according to claim 18 or 19, wherein the cancer is epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer.