Novel Ketooxazole Based Inhibitors of Fatty Acid Amide Hydrolase (FAAH)

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2008 Feb 22

PMID 18289847

Citations 9

Authors

Amy Timmons

Mark Seierstad

Rich Apodaca

Matt Epperson

Dan Pippel

Sean Brown

Leon Chang

Brian Scott

Michael Webb

Sandra R Chaplan

J Guy Breitenbucher

Affiliations

Soon will be listed here.

Abstract

Efforts to improve the properties of the well studied ketooxazole FAAH inhibitor OL-135 resulted in the discovery of a novel propylpiperidine series of FAAH inhibitors that has a modular design and superior properties to OL-135. The efficacy of one of these compounds was demonstrated in a rat spinal nerve ligation model of neuropathic pain in rats.

Citing Articles

On the Biomedical Properties of Endocannabinoid Degradation and Reuptake Inhibitors: Pre-clinical and Clinical Evidence.

Paredes-Ruiz K, Chavira-Ramos K, Orozco-Morales M, Karasu C, Tinkov A, Aschner M Neurotox Res. 2021; 39(6):2072-2097.

PMID: 34741755 DOI: 10.1007/s12640-021-00424-z.

The discovery and development of inhibitors of fatty acid amide hydrolase (FAAH).

Otrubova K, Ezzili C, Boger D Bioorg Med Chem Lett. 2011; 21(16):4674-85.

PMID: 21764305 PMC: 3146581. DOI: 10.1016/j.bmcl.2011.06.096.

Fluoride-mediated capture of a noncovalent bound state of a reversible covalent enzyme inhibitor: X-ray crystallographic analysis of an exceptionally potent α-ketoheterocycle inhibitor of fatty acid amide hydrolase.

Mileni M, Garfunkle J, Ezzili C, Cravatt B, Stevens R, Boger D J Am Chem Soc. 2011; 133(11):4092-100.

PMID: 21355555 PMC: 3060301. DOI: 10.1021/ja110877y.

Fatty acid amide hydrolase as a potential therapeutic target for the treatment of pain and CNS disorders.

Ahn K, Johnson D, Cravatt B Expert Opin Drug Discov. 2010; 4(7):763-784.

PMID: 20544003 PMC: 2882713. DOI: 10.1517/17460440903018857.

X-ray crystallographic analysis of alpha-ketoheterocycle inhibitors bound to a humanized variant of fatty acid amide hydrolase.

Mileni M, Garfunkle J, Ezzili C, Kimball F, Cravatt B, Stevens R J Med Chem. 2009; 53(1):230-40.

PMID: 19924997 PMC: 2804032. DOI: 10.1021/jm9012196.