Cannabinoid receptor agonists

• US 7,217,732 B2
• Filed: 06/17/2003
• Issued: 05/15/2007
• Est. Priority Date: 06/19/2002
• Status: Expired due to Fees

• Current Assignee: Merck Sharp & Dohme Corporation (Merck & Co., Inc.)
• Original Assignee: Schering Corporation (Merck & Co., Inc.)
• Inventors: Shih, Neng-Yang, Tong, Ling, Shankar, Bandarpalle B., Kozlowski, Joseph A.
• Primary Examiner(s): SHAMEEM, GOLAM M
• Application Number:
  US10/464,174
• Publication Number:
  US 20040044051A1
• Time in Patent Office: 1,428 Days
• Field of Search: 548/469, 548/484, 548/486, 548/511, 514/418, 514/415
• US Class Current: 514/418
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 209/12 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 209/14 Radicals substituted by nitrogen atoms, not forming part of a nitro radical
• CPC Class Codes: C07D 209/30 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 213/643 : 2-Phenoxypyridines; Derivatives thereof
• CPC Class Codes: C07D 213/71 : to which a second hetero atom is attached
• CPC Class Codes: C07D 307/64 : Sulfur atoms
• CPC Class Codes: C07D 307/79 : with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 333/34 : Sulfur atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 407/12 : linked by a chain containing hetero atoms as chain links

Abstract

A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein:

• R¹, R², R³, R⁴, R⁵, R⁶, L¹, L², M, n, p, X, Y and Z are as described in the specification; pharmaceutical compositions thereof, methods of making said pharmaceutical compositions; and methods of use thereof.

Claims

1. A compound represented by the structural formula:

2. A compound according to claim 1, wherein L¹ is —

S(O₂)—

.

3. A compound according to claim 1, wherein L² is —

S(O₂)—

.

4. A compound according to claim 1, wherein R¹ is CH₃ or CF₃.

5. A compound according to claim 1, wherein R⁵ and R⁶, which can be the same or different, are H or CH₃.

6. A compound according to claim 1, wherein n is 0.

7. A compound according to claim 1, wherein X is Cl.

8. A compound according to claim 1, wherein Z is a covalent bond, n is 0, R² is H, and R¹, R⁴, R⁵, R⁶, M, L¹, L², p, Y and X are defined in the following table:

9. The compound according to claim 1 having the following formula:

10. The compound according to claim 1 having the following formula:

11. The compound according to claim 1 having the following formula:

12. The compound according to claim 1 having the following formula:

13. The compound according to claim 1 having the following formula:

14. The compound according to claim 1 having the following formula:

15. The compound according to claim 1 having the following formula:

16. The compound according to claim 1 having the following formula:

17. The compound according to claim 1 having the following formula:

18. The compound according to claim 1 having the following formula:

19. The compound according to claim 1 having the following formula:

20. The compound according to claim 1 having the following formula:

21. The compound according to claim 1 having the following formula:

22. The compound according to claim 1 having the following formula:

23. The compound according to claim 1 having the following formula:

24. The compound according to claim 1 wherein said alkyl is in the various definitions of lower alkyl.

25. A pharmaceutical composition comprising one or more compounds according to claim 1.

26. The pharmaceutical composition according to claim 25, further comprising one or more pharmaceutically acceptable carriers.

27. A method of preparing the pharmaceutical composition of claim 26, said method comprising contacting said one or more compounds of formula I with said one or more pharmaceutically acceptable carriers.

28. The compound according to claim 1 having the following formula: