Solid forms of isoquinolinones, and process of making, composition comprising, and methods of using the same

• US 10,160,761 B2
• Filed: 09/13/2016
• Issued: 12/25/2018
• Est. Priority Date: 09/14/2015
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Grenier, Louis, Lescarbeau, Andre, Sharma, Praveen, Genov, Daniel G.
• Primary Examiner(s): O'Dell, David K
• Application Number:
  US15/264,417
• Publication Number:
  US 20170088553A1
• Time in Patent Office: 833 Days
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 231/38 Nitrogen atoms nitro radicals C07D231/16
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Solid forms of chemical compounds that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein. Also provided herein are processes for preparing compounds, polymorphic forms, cocrystals, and amorphous forms thereof, and pharmaceutical compositions thereof.

Claims

1. A solid form of a compound of Formula (I), of a solvate of a compound of Formula (I), or of a cocrystal of a compound of Formula (I):

2. The solid form of claim 1, wherein the solid form is Form 1 of a compound of formula (I), having an X-ray powder diffraction (XRPD) pattern comprising peaks at 16.8, 23.6, and 25.6 degrees 2θ

, plus or minus 0.2.

3. The solid form of claim 2, having an XRPD pattern further comprising at least one peak selected from 14.6 and 21.2 degrees 2θ

, plus or minus 0.2.

4. The solid form of claim 2, having an XRPD pattern substantially as shown in FIG. 1.

5. The solid form of claim 2, which exhibits an endothermic event, as characterized by DSC, with an onset temperature at about 255°

C. and/or a peak temperature at about 257°

C.

6. The solid form of claim 2, which exhibits a weight loss of about 0.6% upon heating from about 230°

C. to about 310°

C.

7. The solid form of claim 2, which exhibits a weight increase of about 0.5% when subjected to an increase in relative humidity from about 0 to about 90% relative humidity.

8. The solid form of claim 2, having approximately unit cell dimensions of:

a=11.1 Å

, b=12.8 Å

, c=16.1 Å

, α

=90°

, β

=90°

, and γ

=90°

.

9. The solid form of claim 2, which is anhydrous.

10. The solid form of claim 2, which is non-hygroscopic.

11. The solid form of claim 1, wherein the solid form is Form 2 of a 1-propanol, acetone, chloroform, or dichloromethane solvate of a compound of formula (I), having an XRPD pattern comprising peaks at 13.6, 14.9, and 21.0 degrees 2θ

, plus or minus 0.2.

12. The solid form of claim 11, having an XRPD pattern further comprising at least one peak selected from 7.4 and 16.7 degrees 2θ

, plus or minus 0.2.

13. The solid form of claim 11, having an XRPD pattern substantially as shown in FIG. 4.

14. The solid form of claim 11, having approximately unit cell dimensions of:

a=8.7 Å

, b=13.2 Å

, c=26.0 Å

, α

=90°

, β

=90°

, and γ

=90°

.

15. The solid form of claim 1, wherein the solid form is Form 3 of a MEK, 1-propanol, acetone, dimethyl sulfoxide, tert-butylmethyl ether, 2-methyl-1-propanol, or 2-methyl THF solvate of a compound of formula (I), having an XRPD pattern comprising peaks at 17.9, 20.6, and 25.8 degrees 2θ

, plus or minus 0.2.

16. The solid form of claim 15, having an XRPD pattern further comprising at least one peak selected from 11.7 and 23.5 degrees 2θ

, plus or minus 0.2.

17. The solid form of claim 15, having an XRPD pattern substantially as shown in FIG. 9.

18. The solid form of claim 1, wherein the solid form is Form 4 of a 2-propanol, 1-propanol, dimethyl sulfoxide, 2-methyl-1-propanol, 1,4-dioxane, chloroform, THF, 2-methoxyethanol, or acetone solvate of a compound of formula (I), having an XRPD pattern comprising peaks at 7.4, 18.0, and 20.7 degrees 2θ

, plus or minus 0.2.

19. The solid form of claim 18, having an XRPD pattern further comprising at least one peak selected from 11.9 and 13.6 degrees 2θ

, plus or minus 0.2.

20. The solid form of claim 18, having an XRPD pattern substantially as shown in FIG. 11.

21. The solid form of claim 1, wherein the solid form is Form 5 of an anisole solvate of a compound of formula (I), having an XRPD pattern comprising peaks at 21.0, 22.1, and 25.2 degrees 2θ

, plus or minus 0.2.

22. The solid form of claim 21, having an XRPD pattern further comprising at least one peak selected from 14.5 and 19.2 degrees 2θ

, plus or minus 0.2.

23. The solid form of claim 21, having an XRPD pattern substantially as shown in FIG. 13.

24. The solid form of claim 1, wherein the solid form is Form 6 of a hydrate of a compound of formula (I), having an XRPD pattern comprising peaks at 4.8, 19.9, and 26.7 degrees 2θ

, plus or minus 0.2.

25. The solid form of claim 24, having an XRPD pattern further comprising at least one peak selected from 11.9 and 24.8 degrees 2θ

, plus or minus 0.2.

26. The solid form of claim 24, having an XRPD pattern substantially as shown in FIG. 15.

27. The solid form of claim 1, wherein the solid form is Form 7 of a MEK, 1-propanol, acetone, or tert-butylmethyl ether solvate of a compound of formula (I), having an XRPD pattern comprising peaks at 7.5, 12.3, and 20.7 degrees 2θ

, plus or minus 0.2.

28. The solid form of claim 27, having an XRPD pattern further comprising at least one peak selected from 13.7 and 17.2 degrees 2θ

, plus or minus 0.2.

29. The solid form of claim 27, having an XRPD pattern substantially as shown in FIG. 18.

30. The solid form of claim 1, wherein the solid form is Form 8 of a compound of formula (I), having an XRPD pattern comprising peaks at 18.8, 20.8, and 24.5 degrees 2θ

, plus or minus 0.2.

31. The solid form of claim 30, having an XRPD pattern further comprising at least one peak selected from 16.0 and 17.9 degrees 2θ

, plus or minus 0.2.

32. The solid form of claim 30, having an XRPD pattern substantially as shown in FIG. 20.

33. The solid form of claim 1, wherein the solid form is Form P1C3 of a cocrystal of a compound of Formula (I) and L-tartaric acid, having an XRPD pattern comprising peaks at 11.2, 17.4, and 17.7 degrees 2θ

, plus or minus 0.2.

34. The solid form of claim 33, having an XRPD pattern further comprising at least one peak selected from 21.2 and 22.5 degrees 2θ

, plus or minus 0.2.

35. The solid form of claim 33, having an XRPD pattern substantially as shown in FIG. 22.

36. The solid form of claim 1, wherein the solid form is Form P1C9 of a cocrystal of a compound of Formula (I) and salicylic acid, having an XRPD pattern comprising peaks at 6.9, 10.1, and 12.0 degrees 2θ

, plus or minus 0.2.

37. The solid form of claim 36, having an XRPD pattern further comprising at least one peak selected from 17.8 and 20.0 degrees 2θ

, plus or minus 0.2.

38. The solid form of claim 36, having an XRPD pattern substantially as shown in FIG. 24.

39. The solid form of claim 1, wherein the solid form is Form P2C9 of a cocrystal of a compound of Formula (I) and salicylic acid, having an XRPD pattern comprising peaks at 11.4, 13.4, and 24.0 degrees 2θ

, plus or minus 0.2.

40. The solid form of claim 39, having an XRPD pattern further comprising at least one peak selected from 25.1 and 26.9 degrees 2θ

, plus or minus 0.2.

41. The solid form of claim 39, having an XRPD pattern substantially as shown in FIG. 26.

42. A pharmaceutical composition comprising a solid form of claim 1 and a pharmaceutical acceptable excipient thereof.

43. A pharmaceutical composition consisting essentially of the solid form of claim 1.