jm0607247_si_001.pdf (120.72 kB)

NO-Donor COX-2 Inhibitors. New Nitrooxy-Substituted 1,5-Diarylimidazoles Endowed with COX-2 Inhibitory and Vasodilator Properties

Download (120.72 kB)
journal contribution
posted on 05.04.2007, 00:00 by Konstantin Chegaev, Loretta Lazzarato, Paolo Tosco, Clara Cena, Elisabetta Marini, Barbara Rolando, Pierre-Alain Carrupt, Roberta Fruttero, Alberto Gasco
A series of NO-donor diarylimidazoles derived from the lead compound Cimicoxib were synthesized and evaluated for their COX-2 inhibitory activity and their stability in whole blood as well as for vasodilator properties. The products are partly transformed into the corresponding alcohols following 24-h incubation in whole blood. All of them display good COX-1/COX-2 selectivity, but are less potent than the lead; a molecular modeling study was carried out to investigate their binding mode. The compounds are also capable of relaxing rat aorta strips precontracted with phenylephrine with a NO-dependent mechanism; this property could confer reduced cardiotoxicity with respect to traditional COX-2 inhibitors.

History

Exports