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.

NO-donor COX-2 inhibitors. New nitrooxy-substituted 1,5-diarylimidazoles endowed with COX-2 inhibitory and vasodilator properties

CHEGAEV, Konstantin;LAZZARATO, Loretta;TOSCO, Paolo;CENA, Clara;MARINI, Elisabetta;ROLANDO, Barbara;FRUTTERO, Roberta;GASCO, Alberto
2007

Abstract

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.
JOURNAL OF MEDICINAL CHEMISTRY
50
7
1449
1457
http://pubs.acs.org/journals/jmcmar/index.html
CHEGAEV K; LAZZARATO L; TOSCO P; CENA C; MARINI E; ROLANDO B; CARRUPT P-A; FRUTTERO R; GASCO A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/41049
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