β-lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase

Marion Feledziak, Catherine Michaux, Allan Urbach, Geoffray Labar, Giulio G. Muccioli, Didier M. Lambert, Jacqueline Marchand-Brynaert

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

Résumé

A library of 30 β-lactams has been prepared from (3R,4R)-3-[(R)- 1′-(tbutyldimethylsilyloxy)-ethyl]-4-acetoxy-2-azetidinone, and the corresponding deacetoxy derivative, by sequential N- and O-functionalizations with various ω-alkenoyl and ω-arylalkanoyl chains. All compounds were selective inhibitors of hFAAH versus hMGL, and IC50 values in the nanomolar range (5-14 nM) were recorded for the best representatives. From time-dependent preincubation and rapid dilution studies, and from docking analyses in a homology model of the target enzyme, a reversible mechanism of inhibition of hFAAH is proposed.

langue originaleAnglais
Pages (de - à)7054-7068
Nombre de pages15
journalJournal of Medicinal Chemistry
Volume52
Numéro de publication22
Les DOIs
Etat de la publicationPublié - 26 nov. 2009

Empreinte digitale Examiner les sujets de recherche de « β-lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase ». Ensemble, ils forment une empreinte digitale unique.

Contient cette citation