Inhibitors of fatty acid amide hydrolase

• US 8,541,581 B2
• Filed: 04/07/2010
• Issued: 09/24/2013
• Est. Priority Date: 04/07/2009
• Status: Expired due to Fees

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Castro, Alfredo C., Evans, Catherine A., Grenier, Louis, Grogan, Michael J.
• Primary Examiner(s): Andres, Janet
• Assistant Examiner(s): Rozof, Timothy R
• Application Number:
  US13/263,324
• Publication Number:
  US 20120088738A1
• Time in Patent Office: 1,266 Days
• Field of Search: None
• US Class Current: 546/13
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

Provided herein are compounds of formula (I): or pharmaceutically acceptable salts, solvates or prodrugs thereof or mixtures thereof, wherein Z¹, Z², X¹, X², X³, R¹, R², R³, R⁴, m and n are defined herein. Also provided are pharmaceutically acceptable compositions that include a compound of formula I and a pharmaceutically acceptable excipient. Also provided are methods for treating an FAAH-mediated disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound or composition of the present invention.

Claims

1. A compound of formula III:

2. The compound of claim 1, wherein R⁸ is selected from —

C(O)R²⁰, —

C(O)NR²²R²³, S(O)₂R₂₄, and —

(CH₂)_p—

R²⁵.

3. The compound of claim 1, wherein R⁸ is —

C(O)R²⁰, and R²⁰ is selected from C_1-6 alkyl, C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —

(CH₂)_q—

R²⁸.

4. The compound of claim 3, wherein R²⁰ is —

(CH₂)_q—

R²⁸, and R²⁸ is selected from C_3-10 carbocyclyl, C_6-10 aryl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl.

5. The compound of claim 3, wherein R²⁰ is —

(CH₂)_q—

R²⁸, and R²⁸ is —

NR³²R³³.

6. The compound of claim 5, wherein R³² and R¹³ each independently is selected from H, C_1-6 alkyl, and C_7-12 aralkyl.

7. The compound of claim 1, wherein R⁸ is —

C(O)NR²²R²³.

8. The compound of claim 7, wherein R²² and R²³ each independently is selected from H, C_1-6 alkyl, and —

(CH₂)_r—

R²⁹.

9. The compound of claim 8 wherein R²⁹ is selected from C_6-10 aryl and 5-10 membered heteroaryl.

10. The compound of claim 1, wherein R⁸ is —

S(O)₂R²⁴.

11. The compound of claim 10, wherein R²⁴ is selected from C_1-6 alkyl, C_6-10 aryl, 5-10 membered heteroaryl, and —

(CH₂)_t—

R³⁰.

12. The compound of claim 1, wherein R⁸ is —

(CH₂)_p—

R²⁵.

13. The compound of claim 12, wherein R²⁵ is selected from C_6-10 aryl and 5-10 membered heteroaryl.

14. The compound of claim 1, wherein R¹² is H and R¹³ is H.

15. The compound of claim 1, wherein R⁶ is H and R⁷ is H.

16. The compound of claim 1, wherein is a double bond and m is 0.

17. The compound of claim 1, wherein is a single bond and m is 1.

18. The compound of claim 17, wherein R² is H.

19. The compound of claim 1, wherein R¹ is H.

20. The compound of claim 1, wherein R³ is H and R⁴ is H.

21. The compound of claim 1, wherein R¹⁴ is H and R¹⁵ is H.

22. The compound of claim 1, wherein the compound is selected from:

23. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof and a pharmaceutically acceptable excipient.

24. The compound of claim 1, wherein the compound is of the formula IIIa:

25. The compound of claim 1, wherein the compound is of the formula IIIb: