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

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Chegaev K, Lazzarato L, Tosco P, Cena C, Marini E, Rolando B, Carrupt PA, Fruttero R, Gasco A

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

J Med Chem. 2007 Apr 5;50(7):1449-57. Epub 2007 Mar 3.

PubMed ID

17335184 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drugs

Cimicoxib

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Cimicoxib	Prostaglandin G/H synthase 2	Protein	Humans	Unknown	Inhibitor	Details

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Celecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	1300	N/A	N/A	Details
Cimicoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	100	N/A	N/A	Details
Rofecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	1500	N/A	N/A	Details