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Beta-Lactams Derived From A Carbapenem Chiron Are Selective Inhibitors Of Human Fatty Acid Amide Hydrolase Versus Human Monoacylglycerol Lipase.
Marion Feledziak, C. Michaux, A. Urbach, G. Labar, G. Muccioli, D. Lambert, J. Marchand-Brynaert
Published 2009 · Chemistry, Medicine
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A library of 30 beta-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 omega-alkenoyl and omega-arylalkanoyl chains. All compounds were selective inhibitors of hFAAH versus hMGL, and IC(50) 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.
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