3-Alkenyl-2-azetidinones as fatty acid amide hydrolase inhibitors.
A series of novel 2-azetidinones (beta-lactams) bearing short alkenyl chains at C3 and N1 have been prepared and evaluated in vitro as inhibitors of human FAAH. Compound 9c (1-(4'-pentenoyl-3-(4'-pentenyl)-2-azetidinone)) featured an IC(50) value of 4.5 microM and a good selectivity for FAAH versus MGL.
Urbach
Allan
A
Unité de chimie organique et médicinale, Université catholique de Louvain, Bâtiment Lavoisier, Place Louis Pasteur n degrees 1, 1348 Louvain-la-Neuve, Belgium.
Muccioli
Giulio G
GG
Stern
Eric
E
Lambert
Didier M
DM
Marchand-Brynaert
Jacqueline
J
D000581:Amidohydrolases / Q000037:antagonists & inhibitors*; D000818:Animals; D001384:Azetidines / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D013552:Swine; D047090:beta-Lactams / Q000737:chemistry; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D001384:Azetidines; D004791:Enzyme Inhibitors; D010196:Pancreatic Elastase; D047090:beta-Lactams; D000099252:Fatty Acid Amide Hydrolases; C116379:2-azetidinone