Unknown

Dataset Information

0

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.

SUBMITTER: Boger DL 

PROVIDER: S-EPMC2492884 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

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

Boger Dale L DL   Miyauchi Hiroshi H   Du Wu W   Hardouin Christophe C   Fecik Robert A RA   Cheng Heng H   Hwang Inkyu I   Hedrick Michael P MP   Leung Donmienne D   Acevedo Orlando O   Guimarães Cristiano R W CR   Jorgensen William L WL   Cravatt Benjamin F BF  

Journal of medicinal chemistry 20050301 6

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  ...[more]

Similar Datasets

Unknown Reversible competitive ?-ketoheterocycle inhibitors of fatty acid amide hydrolase containing additional conformational constraints in the acyl side chain: orally active, long-acting analgesics.
| S-EPMC3085948 | biostudies-literature
Unknown Potent and selective alpha-ketoheterocycle-based inhibitors of the anandamide and oleamide catabolizing enzyme, fatty acid amide hydrolase.
| S-EPMC2531193 | biostudies-literature
Unknown α-Ketoheterocycle-based Inhibitors of Fatty Acid Amide Hydrolase (FAAH).
| S-EPMC3359644 | biostudies-other
Unknown Exploration of a fundamental substituent effect of alpha-ketoheterocycle enzyme inhibitors: Potent and selective inhibitors of fatty acid amide hydrolase.
| S-EPMC2582052 | biostudies-literature
Unknown Fluoride-mediated capture of a noncovalent bound state of a reversible covalent enzyme inhibitor: X-ray crystallographic analysis of an exceptionally potent ?-ketoheterocycle inhibitor of fatty acid amide hydrolase.
| S-EPMC3060301 | biostudies-literature
Unknown Discovery of Uracil Derivatives as Potent Inhibitors of Fatty Acid Amide Hydrolase.
| S-EPMC6274076 | biostudies-literature
Unknown Optimization of the central heterocycle of alpha-ketoheterocycle inhibitors of fatty acid amide hydrolase.
| S-EPMC2556205 | biostudies-literature
Unknown Discovery and molecular basis of potent noncovalent inhibitors of fatty acid amide hydrolase (FAAH).
| S-EPMC3088576 | biostudies-literature
Unknown α-Ketoheterocycle inhibitors of fatty acid amide hydrolase: exploration of conformational constraints in the acyl side chain.
| S-EPMC4029506 | biostudies-literature
Unknown X-ray crystallographic analysis of alpha-ketoheterocycle inhibitors bound to a humanized variant of fatty acid amide hydrolase.
| S-EPMC2804032 | biostudies-literature