Beta-lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase
(2009) Journal of Medicinal Chemistry — Vol. 52, n° 22, p. 7054-7068 (2009)
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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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Feledziak, M., Michaux, C., Urbach, A., Labar, G., Muccioli, G., Lambert, D., & Marchand-Brynaert, J. (2009). Beta-lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase. Journal of Medicinal Chemistry, 52(22), 7054-7068. https://doi.org/10.1021/jm9008532 (Original work published 2009)