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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aorta / drug effects
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Aorta / physiology
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Cyclooxygenase 2 Inhibitors / chemical synthesis*
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / pharmacology
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Humans
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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In Vitro Techniques
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Models, Molecular
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Muscle Contraction / drug effects
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / physiology
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Nitric Oxide Donors / chemical synthesis*
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Nitric Oxide Donors / chemistry
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Nitric Oxide Donors / pharmacology
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Rats
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Structure-Activity Relationship
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Sulfonamides / chemical synthesis*
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Sulfonamides / chemistry
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Sulfonamides / pharmacology
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Vasodilator Agents / chemical synthesis*
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Vasodilator Agents / chemistry
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Vasodilator Agents / pharmacology
Substances
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Cyclooxygenase 2 Inhibitors
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Imidazoles
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Nitric Oxide Donors
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Sulfonamides
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Vasodilator Agents
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cimicoxib