Salts and crystall forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile

• US 20130289064A1
• Filed: 04/04/2013
• Published: 10/31/2013
• Est. Priority Date: 11/20/2006
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Stowasser, Frank, Banziger, Markus, Garad, Sudhakar Devidasrao
• Application Number:
  US13/856,458
• Publication Number:
  US 20130289064A1
• Time in Patent Office: Days
• US Class Current: 514/293
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07C 309/30 of six-membered aromatic rings substituted by alkyl groups
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

The invention relates to particular crystalline forms of 2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-yl-2,3-dihydro-imidazo[4,5-c]quinolin-1-yl)-phenyl]-propionitrile, its hydrates and solvates, its salts and hydrates and solvates of its salts, certain processes for their preparation, pharmaceutical compositions containing these crystalline forms, and their use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans.

Claims

1. A crystalline form of the compound of formula I

2. Compound I according to claim 1 in crystalline form A.

3. A compound according to claim 2 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 8.4°

+/−

0.3°

.

4. Compound I according to claim 1 in crystalline form B.

5. A compound according to claim 3 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.9°

+/−

0.3°

.

6. Compound I according to claim 1 in crystalline form C.

7. A compound according to claim 6 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 14.7°

+/−

0.3°

.

8. Compound I according to claim 1 in crystalline form D.

9. A compound according to claim 8 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 23.9°

+/−

0.3°

.

10. A monohydrate of compound 1 according to claim 1 in crystalline form H_A.

11. A compound according to claim 10 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 17.6°

+/−

0.3°

.

12. A monotosylate salt of compound I according to claim 1 in crystalline form.

13. A monotosylate salt of compound I according to claim 12 in crystalline form A.

14. A compound according to claim 12 or 13 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.7°

+/−

0.3°

.

15. A compound according to claim 12, 13 or 14 which shows on X-ray diffraction peaks at an angle of diffraction 2Theta of 5.4°

+/−

0.3°

;

5.7°

+/−

0.3° and

17.2°

+/−

0.3°

.

16. A compound according to claim 12 or 13 which shows an X-ray diffraction diagram essentially as outlined in FIG. 6.

17. A monotosylate salt of compound I according to claim 12 in crystalline form B.

18. A compound according to claim 12 or 17 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.8°

+/−

0.3°

.

19. A compound according to claim 12, 17 or 18 which shows on X-ray diffraction peaks at an angle of diffraction 2Theta of 5.8°

+/−

0.3°

;

17.8°

+/−

0.3° and

18.7°

+/−

0.3°

.

20. A monohydrate of the monotosylate salt of compound I according to claim 1 in crystalline form H_A.

21. A compound according to claim 20 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.5°

+/−

0.3°

.

22. A dihydrate of the monotosylate salt of compound I according to claim 1 in crystalline form H_B.

23. A compound according to claim 22 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 6.9°

+/−

0.3°

.

24. A diformic acid solvate of the monotosylate salt of compound I according to claim 1 in crystalline form S_A.

25. A compound according to claim 24 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.8°

+/−

0.3°

.

26. A ditosylate salt of compound I according to claim 1 in crystalline form.

27. A ditosylate salt of compound I according to claim 26 in crystalline form A.

28. A compound according to claim 26 or 27 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 22.4°

+/−

0.3°

.

29. A trihydrate of the ditosylate salt of compound I according to claim 1 in crystalline form H_A.

30. A compound according to claim 29 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 4.7°

+/−

0.3°

.

31. An amorphous monotosylate salt of compound I according to claim 1.

32. A monohydrate of the diformic acid solvate of the monotosylate salt of compound I according to claim 1 in crystalline form S_C.

33. A compound according to claim 32 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.6°

+/−

0.3°

.

34. A diacetic acid solvate of the monotosylate salt of compound I according to claim 1 in crystalline form S_B.

35. A compound according to claim 34 which shows on X-ray diffraction a peak at an angle of diffraction 2Theta of 5.7°

+/−

0.3°

.

36. The solid form of the compound of formula I or of a hydrate or solvate of the compound of formula I, or of a salt of the compound of formula I, or of a hydrate or solvate of a salt of the compound of formula I according to any one of the claims 1 to 35, which is present in essentially pure form.

37. A pharmaceutical composition comprising a solid form of the compound of formula I, its hydrates or solvates, its salts and hydrates or solvates of its salts according to any one of the claims 1 to 35, and optionally at least one pharmaceutically acceptable carrier.

38. The use of a solid form of the compound of formula I, its hydrates or solvates, its salts and hydrates or solvates of its salts according to any one of the claims 1 to 35 for the preparation of a medicament for the treatment of treatment of a proliferative disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, sarcoma, glioblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, lymphomas, a mammary carcinoma or a leukemia. Other diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3k/PKB pathway is aberrantly activated.

39. Method of treating a disease selected from a benign or malignant tumor, carcinoma of the brain, kidney, liver, adrenal gland, bladder, breast, stomach, gastric tumors, ovaries, colon, rectum, prostate, pancreas, lung, vagina or thyroid, sarcoma, glioblastomas, multiple myeloma or gastrointestinal cancer, especially colon carcinoma or colorectal adenoma or a tumor of the neck and head, an epidermal hyperproliferation, psoriasis, prostate hyperplasia, a neoplasia, a neoplasia of epithelial character, lymphomas, a mammary carcinoma or a leukemia. Other diseases include Cowden syndrome, Lhermitte-Dudos disease and Bannayan-Zonana syndrome, or diseases in which the PI3K/PKB pathway is aberrantly activated in a warm-blooded animal in need thereof comprising administering to the animal a crystalline form of the compound of formula I, its hydrates or solvates, its salts or hydrates or solvates of its salts according to any one of the claims 1 to 35 in a quantity which is therapeutically effective against the respective disease.