beta-Lactams derived from a carbapenem chiron are selective inhibitors of human fatty acid amide hydrolase versus human monoacylglycerol lipase.
J Med Chem
; 52(22): 7054-68, 2009 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-19877691
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Carbapenêmicos
/
Inibidores Enzimáticos
/
Amidoidrolases
/
Monoacilglicerol Lipases
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article