SOLID FORMS OF SULFONAMIDES AND AMINO ACIDS

• US 20120122860A1
• Filed: 05/04/2010
• Published: 05/17/2012
• Est. Priority Date: 05/06/2009
• Status: Abandoned Application

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Ibrahim, Prabha N., Spevak, Wayne, Shi, Songyuan, Wu, Guoxian, Visor, Gary Conard, Cho, Hanna
• Application Number:
  US13/318,760
• Publication Number:
  US 20120122860A1
• Time in Patent Office: Days
• US Class Current: 514/230.5
• CPC Class Codes: A61P 13/12 of the kidneys
• 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 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: C07D 471/04 Ortho-condensed systems

Abstract

Solid forms of phenyl sulfonamide compounds of formula (I) active on protein kinases, including Raf protein kinases, are described, as well as methods of using such solid forms to treat diseases and conditions associated with activity of protein kinases, e.g. Raf protein kinases, including pain, polycystic kidney disease, melanoma and colorectal cancer.

Claims

1. A solid form of a phenyl sulfonamide compound comprising a basic amino acid and the phenyl sulfonamide compound of Formula I

2. The solid form of claim 1, wherein the sulfonamide compound is a compound of Formula Ia

3. The solid form of claim 2, wherein the sulfonamide compound is a compound selected from the group consisting of

4. The solid form of claim 3, wherein the basic amino acid is L-lysine or L-arginine

5. The solid form of claim 3, wherein the solid form is an amorphous complex.

6. The solid form of claim 5, wherein R⁵⁶ is lower alkyl, di-alkylamino, cycloalkylamino, or phenyl substituted with one or more fluoro, lower alkyl, or fluoro substituted lower alkyl.

7. The solid form of claim 6, wherein R⁵⁶ is n-propyl, di-methylamino, pyrrolidin-1-yl, 3-fluoro phenyl, or 2,5-di-fluoro phenyl.

8. The solid form of claim 7, wherein the compound is propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide and the basic amino acid is L-lysine or L-arginine.

10. The solid form of claim 7, wherein the compound is propane-1-sulfonic acid {2,4-difluoro-3-[5-(2-methoxy-pyrimidin-5-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-phenyl}-amide and the basic amino acid is L-lysine or L-arginine.

12. The solid form of claim 6, wherein R⁵⁶ is 4-t-butyl phenyl, 3-trifluoromethyl phenyl or 4-trifluoromethyl phenyl.

13. The solid form of claim 12, wherein the compound is N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-trifluoromethyl-benzenesulfonamide and the basic amino acid is L-lysine or L-arginine.

15. The solid form of claim 12, wherein the compound is N-[3-(5-cyano-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluoro-phenyl]-4-trifluoromethyl-benzenesulfonamide and the basic amino acid is L-lysine or L-arginine.

17. A composition comprising the solid form of claim 1 and one or more pharmaceutically acceptable excipients.

22. A composition comprising the solid form of claim 8 and one or more pharmaceutically acceptable excipients.

23. A composition comprising the solid form of claim 10 and one or more pharmaceutically acceptable excipients.

24. A composition comprising the solid form of claim 12 and one or more pharmaceutically acceptable excipients.

25. A composition comprising the solid form of claim 13 and one or more pharmaceutically acceptable excipients.

26. A composition comprising the solid form of claim 15 and one or more pharmaceutically acceptable excipients.

9. (canceled)

11. (canceled)

14. (canceled)

16. (canceled)

18. A method of making an amorphous complex comprising propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide and, said method comprising contacting crystalline polymorph Form 1 of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide with an amino acid selected from L-lysine or L-arginine under conditions sufficient for the preparation of said complex.

19. (canceled)

20. A method of making an amorphous complex comprising propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide and L-lysine, said method comprising contacting crystalline polymorph Form 2 of propane-1-sulfonic acid {3-[5-(4-chloro-phenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide with an amino acid selected from L-lysine or L-arginine under conditions sufficient for the preparation of said complex.

21. (canceled)