Cannabinoid receptor modulators

Patent metadata

Field	Value
Publication number	US-9944606-B2
Application number	US-201213616918-A
Country	US
Kind code	B2
Filing date	Sep 14, 2012
Priority date	Aug 28, 2009
Publication date	Apr 17, 2018
Grant date	Apr 17, 2018

Abstract

The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

First claim

What is claimed is:

1. A method for the treatment of pain and/or osteoarthritis in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of the following compound and pharmaceutically acceptable salts, solvates, and hydrates thereof:
(1aS,5aS)-2-Pyrazin-2-yl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide (Compound 696).

2. A method for the treatment of pain and/or osteoarthritis in an individual in need thereof, comprising administering to said individual a therapeutically effective amount of the following compound and pharmaceutically acceptable salts, solvates, and hydrates thereof:
(1aS,5aS)-2-(4-Oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide (Compound 699).

3. The method according to claim 1 , wherein the method is for the treatment of osteoarthritis.

4. The method according to claim 2 , wherein the method is for the treatment of osteoarthritis.

5. The method according to claim 1 , wherein the method is for the treatment of pain.

6. The method according to claim 1 , wherein the method is for the treatment of pain.

7. The method of claim 1 , wherein (1aS,5aS)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

8. The method of claim 1 , wherein a pharmaceutically acceptable salt of (1aS,5aS)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

9. The method of claim 1 , wherein a solvate of (1aS,5aS)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

10. The method of claim 1 , wherein a hydrate of (1aS,5aS)-2-pyrazin-2-yl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

11. The method of claim 2 , wherein (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

12. The method of claim 2 , wherein a pharmaceutically acceptable salt of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

13. The method of claim 2 , wherein a solvate of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

14. The method of claim 2 , wherein a hydrate of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)-1-hydroxymethyl-2,2-dimethyl-propyl)-amide is administered to said individual in need thereof.

15. The method according to claim 7 , wherein the method is for the treatment of osteoarthritis.

16. The method according to claim 7 , wherein the method is for the treatment of pain.

17. The method according to claim 8 , wherein the method is for the treatment of osteoarthritis.

18. The method according to claim 8 , wherein the method is for the treatment of pain.

19. The method according to claim 9 , wherein the method is for the treatment of osteoarthritis.

20. The method according to claim 9 , wherein the method is for the treatment of pain.

21. The method according to claim 10 , wherein the method is for the treatment of osteoarthritis.

22. The method according to claim 10 , wherein the method is for the treatment of pain.

23. The method according to claim 11 , wherein the method is for the treatment of osteoarthritis.

24. The method according to claim 11 , wherein the method is for the treatment of pain.

25. The method according to claim 12 , wherein the method is for the treatment of osteoarthritis.

26. The method according to claim 12 , wherein the method is for the treatment of pain.

27. The method according to claim 13 , wherein the method is for the treatment of osteoarthritis.

28. The method according to claim 13 , wherein the method is for the treatment of pain.

29. The method according to claim 13 , wherein the method is for the treatment of osteoarthritis.

30. The method according to claim 13 , wherein the method is for the treatment of pain.

Assignees

• Jones Robert M
• Han Sangdon
• THORESEN Lars
• Jung Jae Kyu
• Strah Pleynet Sonja
• Zhu Xiuwen
• Xiong Yifeng
• Yue Dawei
• Arena Pharm Inc

Inventors

• Jones Robert M
• Han Sangdon
• THORESEN Lars
• Jung Jae-Kyu
• Strah-Pleynet Sonja
• Zhu Xiuwen
• Xiong Yifeng
• Yue Dawei

Classifications

• A61P29/00

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

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D403/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title