TRPV1 antagonists including dihydroxy substituent and uses thereof

Patent metadata

Field	Value
Publication number	US-9630959-B2
Application number	US-201615018493-A
Country	US
Kind code	B2
Filing date	Feb 8, 2016
Priority date	Jun 22, 2011
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

The disclosure relates to Compounds of Formula (I)

and pharmaceutically acceptable derivatives thereof, where R 1 , R 4 , R 8 , R 9 , and m are as defined herein, compositions comprising an effective amount of a Compound of Formula (I) or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, pain associated with osteoarthritis, osteoarthritis, UI, an ulcer, IBD, and IBS, comprising administering to an animal in need thereof an effective amount of a Compound of Formula (I) or a pharmaceutically acceptable derivative thereof.

First claim

What is claimed:

1. A co-crystal of (a) a compound which is

and (b) fumaric acid, wherein said co-crystal is characterized by a CP/MAS 13 C NMR spectrum comprising peaks with a chemical shift of 171.5±0.2 ppm, 170.3±0.2 ppm, and 135.6±0.2 ppm when measured by the CP/MAS 13 C NMR procedure described in Example 10.

2. The co-crystal of claim 1 , wherein said co-crystal is characterized by a CP/MAS 13 C NMR spectrum further comprising a peak with a chemical shift of 72.2±0.2 ppm when measured by the CP/MAS 13 C NMR procedure described in Example 10.

3. The co-crystal of claim 1 , wherein said co-crystal is characterized by a CP/MAS 13 C NMR spectrum further comprising peaks with a chemical shift of 72.2±0.2 ppm and 15.1±0.2 ppm when measured by the CP/MAS 13 C NMR procedure described in Example 10.

4. The co-crystal of claim 1 , wherein the molar ratio of the compound to fumaric acid is from about 1.0:0.4 to about 1.0:0.7.

5. A co-crystal of (a) a compound which is

and (b) fumaric acid, wherein said co-crystal is characterized by an x-ray powder diffraction pattern comprising a peak at each of 6.5, 12.5, 16.8, and 25.3 degrees 2θ±0.2° when measured using CuKα radiation.

6. The co-crystal of claim 5 , wherein said co-crystal is characterized by an x-ray powder diffraction pattern further comprising peaks at 8.6, 14.0, and 18.7 degrees 2θ±0.2° when measured using CuKα radiation.

7. The co-crystal of claim 5 , wherein the molar ratio of the compound to fumaric acid is from about 1.0:0.4 to about 1.0:0.7.

8. A product obtained from a process comprising a step of combining a compound of formula

with fumaric acid, wherein said product is characterized by a CP/MAS 13 C NMR spectrum comprising peaks with a chemical shift of 171.5±0.2 ppm, 170.3±0.2 ppm, and 135.6±0.2 ppm when measured by the CP/MAS 13 C NMR procedure described in Example 10.

9. The product of claim 8 , wherein said product is characterized by a CP/MAS 13 C NMR spectrum further comprising a peak with a chemical shift of 72.2±0.2 ppm when measured by the CP/MAS 13 C NMR procedure described in Example 10.

10. The product of claim 8 , wherein said product is characterized by a CP/MAS 13 C NMR spectrum further comprising peaks with a chemical shift of 72.2±0.2 ppm and 15.1±0.2 ppm when measured by the CP/MAS 13 C NMR procedure described in Example 10.

11. The product of claim 8 , wherein the molar ratio of the compound to fumaric acid is about 1.0:0.5.

12. A product obtained from a process comprising a step of combining a compound of formula

with fumaric acid, wherein said product is characterized by an x-ray powder diffraction pattern comprising a peak at each of 6.5, 12.5, 16.8, and 25.3 degrees 2θ±0.2° when measured using CuKα radiation.

13. The product of claim 12 , wherein said product is characterized by an x-ray powder diffraction pattern further comprising peaks at 8.6, 14.0, and 18.7 degrees 2θ±0.2° when measured using CuKα radiation.

14. The product of claim 12 , wherein the molar ratio of the compound to fumaric acid is about 1.0:0.5.

15. A pharmaceutical composition comprising the co-crystal of claim 1 and a pharmaceutically acceptable carrier or excipient.

16. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the co-crystal of claim 1 .

17. A method of inhibiting TRPV1 function in a cell comprising contacting a cell capable of expressing TRPV1 with an effective amount of the co-crystal of claim 1 .

18. A pharmaceutical composition comprising the co-crystal of claim 4 and a pharmaceutically acceptable carrier or excipient.

19. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the co-crystal of claim 4 .

20. A method of inhibiting TRPV1 function in a cell comprising contacting a cell capable of expressing TRPV1 with an effective amount of the co-crystal of claim 4 .

21. A pharmaceutical composition comprising the co-crystal of claim 5 and a pharmaceutically acceptable carrier or excipient.

22. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the co-crystal of claim 5 .

23. A method of inhibiting TRPV1 function in a cell comprising contacting a cell capable of expressing TRPV1 with an effective amount of the co-crystal of claim 5 .

24. A pharmaceutical composition comprising the co-crystal of claim 7 and a pharmaceutically acceptable carrier or excipient.

25. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the co-crystal of claim 7 .

26. A method of inhibiting TRPV1 function in a cell comprising contacting a cell capable of expressing TRPV1 with an effective amount of the co-crystal of claim 7 .

27. The co-crystal of claim 1 , wherein the molar ratio of the compound to fumaric acid is about 1.0:0.5.

28. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the co-crystal of claim 27 .

29. The co-crystal of claim 5 , wherein the molar ratio of the compound to fumaric acid is about 1.0:0.5.

30. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the co-crystal of claim 29 .

31. The product of claim 8 , wherein the molar ratio of the compound to fumaric acid is from about 1.0:0.4 to about 1.0:0.7.

32. The product of claim 12 , wherein the molar ratio of the compound to fumaric acid is from about 1.0:0.4 to about 1.0:0.7.

33. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof, an effective amount of the product of claim 11 .

34. A method for treating inflammatory pain, pain associated with osteoarthritis, or neuropathic pain in an animal, comprising administering to an animal in need thereof an effective amount of the product of claim 14 .

Assignees

• Purdue Pharma Lp
• Shionogi & Co

Inventors

• Ando Shigeru
• Kurose Noriyuki
• Tafesse Laykea

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P1/04

  for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants · CPC title