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Discovery of a potent, selective, and efficacious class of reversible alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase effective as analgesics.

Abstract：

:Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routine implementation of a proteomics-wide selectivity screen against the serine hydrolase superfamily ensuring selectivity for FAAH coupled with systematic in vivo examinations of candidate inhibitors.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Boger DL,Miyauchi H,Du W,Hardouin C,Fecik RA,Cheng H,Hwang I,Hedrick MP,Leung D,Acevedo O,Guimarães CR,Jorgensen WL,Cravatt BF

doi

10.1021/jm049614v

keywords:

subject

Has Abstract

pub_date

2005-03-24 00:00:00

pages

1849-56

issue

6

eissn

0022-2623

issn

1520-4804

journal_volume

48

pub_type

杂志文章

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