1. J Med Chem. 2009 Nov 26;52(22):7054-7068.

beta-Lactams Derived from a Carbapenem Chiron Are Selective Inhibitors of Human
Fatty Acid Amide Hydrolase versus Human Monoacylglycerol Lipase.

Feledziak M, Michaux C, Urbach A, Labar G, Muccioli GG, Lambert DM,
Marchand-Brynaert J.

Unite de Chimie Organique et Medicinale, Universite Catholique de Louvain,
Batiment Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-La-Neuve, Belgium.

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.

PMID: 19877691 [PubMed - as supplied by publisher]