TRPV1 antagonists including dihydroxy substituent and uses thereof

Patent metadata

Field	Value
Publication number	US-10450308-B2
Application number	US-201715455427-A
Country	US
Kind code	B2
Filing date	Mar 10, 2017
Priority date	Jun 22, 2011
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

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 method for treating pain in an animal, comprising administering to an animal in need thereof, an effective amount of a compound of formula (I):

or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof,
wherein:
R 1 is —F;
R 4 is —H or —CH 3 ;
each R 8 and R 9 is independently —H, —F, —Cl or —CH 3 ;
R 10 is —(C 1 -C 4 )alkyl;
m is 1; and
the methyl group bonded to the piperazine ring is a (S)-2-methyl group.

2. A method for treating pain in an animal, comprising administering to an animal in need thereof, an effective amount of a compound of formula (II):

or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof,
wherein:
R 4 is —H or —CH 3 ;
R 8 is —H, —F, or —CH 3 ; and
R 9 is —H, —F, —Cl or —CH 3 ;
and the methyl group bonded to the piperazine ring is a (S)-2-methyl group or a (S)-3-methyl group.

3. The method of claim 2 , wherein R 4 of the compound of formula (II) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —H and the carbon atom at the a position of the a-b bond is in the (S) configuration.

4. The method of claim 2 , wherein R 9 of the compound of formula (II) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —H.

5. The method of claim 2 , wherein R 8 of the compound of formula (II) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —F.

6. A method for treating pain in an animal, comprising administering to an animal in need thereof, an effective amount of a compound or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof, wherein the compound is:

7. The method of claim 1 , wherein R 9 of the compound of formula (I) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —H, —F, or Cl.

8. The method of claim 1 , wherein R 8 of the compound of formula (I) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —H, —F, or —CH 3 .

9. The method of claim 1 , wherein the pharmaceutically acceptable salt, the fumarate co-crystal, or the combination thereof is a hydrochloride salt, a sodium salt, a potassium salt, a p-toluenesulfonic acid salt, a fumaric acid-salt, or a fumarate co-crystal.

10. The method of claim 1 , wherein the pharmaceutically acceptable salt, the fumarate co-crystal, or the combination thereof is a fumaric acid-salt, a fumarate co-crystal, or a combination thereof.

11. The method of claim 1 , wherein the pain is chronic or acute pain.

12. The method of claim 1 , wherein the pain is a pain associated with osteoarthritis, cancer pain, neuropathic pain, labor pain, myocardial infarction pain, pancreatic pain, colic pain, post-operative pain, headache pain, muscle pain, arthritic pain, pain associated with a periodontal disease, pain associated with inflammation, or pain associated with an inflammatory disease.

13. A method for treating pain in an animal, comprising administering to an animal in need thereof, an effective amount of a compound or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof, wherein the compound is:

14. The method of claim 13 , wherein the pain is chronic or acute pain.

15. The method of claim 13 , wherein the pain is a pain associated with osteoarthritis, cancer pain, neuropathic pain, labor pain, myocardial infarction pain, pancreatic pain, colic pain, post-operative pain, headache pain, muscle pain, arthritic pain, pain associated with a periodontal disease, pain associated with inflammation, or pain associated with an inflammatory disease.

16. The method of claim 2 , wherein the methyl group bonded to the piperazine ring is a (S)-2-methyl group.

17. The method of claim 2 , wherein the methyl group bonded to the piperazine ring is a (S)-3-methyl group.

18. The method of claim 2 , wherein R 4 of the compound of formula (II) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —CH 3 , the carbon atom at the a position of the a-b bond is in the (S) configuration, and the carbon atom at the c position of the c-d bond is in the (S) configuration.

19. The method of claim 2 , wherein R 4 of the compound of formula (II) or a pharmaceutically acceptable salt, a fumarate co-crystal, or a combination thereof is —CH 3 , the carbon atom at the a position of the a-b bond is in the (R) configuration, and the carbon atom at the c position of the c-d bond is in the (R) configuration.

20. The method of claim 2 , wherein the pain is chronic or acute pain.

21. The method of claim 2 , wherein the pain is a pain associated with osteoarthritis, cancer pain, neuropathic pain, labor pain, myocardial infarction pain, pancreatic pain, colic pain, post-operative pain, headache pain, muscle pain, arthritic pain, pain associated with a periodontal disease, pain associated with inflammation, or pain associated with an inflammatory disease.

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

• A61P25/00

  Drugs for disorders of the nervous system · CPC title