Abstract
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.
Original language | English |
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Pages (from-to) | 7054-7068 |
Number of pages | 15 |
Journal | Journal of Medicinal Chemistry |
Volume | 52 |
Issue number | 22 |
DOIs | |
Publication status | Published - 26 Nov 2009 |