Isoxazolines as inhibitors of fatty acid amide hydrolase

• US 9,149,465 B2
• Filed: 05/18/2010
• Issued: 10/06/2015
• Est. Priority Date: 05/18/2009
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Behnke, Mark L., Castro, Alfredo C., Chan, Lawrence K., Evans, Catherine A., Grenier, Louis, Grogan, Michael J., Leblanc, Yves, Liu, Tao, Peluso, Stephane, Snyder, Daniel A., Tibbitts, Thomas T.
• Primary Examiner(s): Pagonakis, Anna
• Application Number:
  US12/782,650
• Publication Number:
  US 20110028478A1
• Time in Patent Office: 1,967 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/4245 Oxadiazoles
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/501 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 261/04 having one double bond between ring members or between a ring member and a non-ring member
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems

Abstract

The present invention provides isoxazoline FAAH inhibitors of the formula (I):

• • or pharmaceutically acceptable forms thereof, wherein each of G, R^a, R^b, R^c, and R^d are as defined herein.

The present invention also provides pharmaceutical compositions comprising a compound of formula (I), or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient.

The present invention also provides methods for treating an FAAH-mediated condition comprising administering a therapeutically effective amount of a compound of formula (I), or pharmaceutically acceptable form thereof, to a subject in need thereof.

Claims

1. A compound of the formula:

2. A pharmaceutical composition comprising a compound of the formula:

3. A compound of the formula:

4. A pharmaceutical composition comprising a compound of claim 3, or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient.

6. A pharmaceutical composition comprising the compound of claim 3, or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient.

5. The compound:

7. The compound of claim 5, wherein the compound is a (R)-enantiomer.

8. The compound of claim 5, wherein the compound is the (R)-enantiomer having an enantiomeric purity greater than 75%.

9. The compound of claim 5, wherein the compound is the (R)-enantiomer having an enantiomeric purity greater than 90%.

10. The compound of claim 5, wherein the compound is the (R)-enantiomer having an enantiomeric purity greater than 95%.