A new class of acyclic 2-alkyl-1,1,2-triaryl (Z)-olefins as selective cyclooxygenase-2 inhibitors.

doi:10.1021/JM049523Y

Paper

A new class of acyclic 2-alkyl-1,1,2-triaryl (Z)-olefins as selective cyclooxygenase-2 inhibitors.

Published Oct 19, 2004 · M. Uddin, P. N. Praveen Rao, R. McDonald

Journal of medicinal chemistry

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32

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1

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Abstract

A new class of acyclic (Z)-2-alkyl-1,2-diphenyl-1-(4-methanesulfonylphenyl)ethenes (7) was designed for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition structure-activity studies identified (Z)-1,2-diphenyl-1-(4-methanesulfonylphenyl)oct-1-ene (7d) as a potent COX-2 inhibitor (IC(50) = 0.42 microM) with a high COX-2 selectivity index (SI > 234). In a carrageenan-induced rat paw edema assay, (Z)-7d exhibited excellent antiinflammatory activity (ID(50) = 1.1 mg/kg). The molecular modeling and structure-activity data acquired indicate that (Z)-olefins having cis C-1 4-methanesulfonylphenyl and C-2 unsubstituted phenyl (or 4-acetoxyphenyl) substituents in conjunction with a C-1 phenyl ring and a C-2 alkyl substituent of appropriate length constitute a suitable template for the design of a novel class of acyclic (Z)-2-alkyl-1,1,2-triaryleth-1-ene COX-2 inhibitors.

In Vitro Study

Study Snapshot

The new class of acyclic (Z)-2-alkyl-1,2-diphenyl-1-(4-methanesulfonylphenyl)ethenes (7) shows potent COX-2 inhibitory activity and excellent antiinflammatory activity.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

A new class of acyclic 2-alkyl-1,1,2-triaryl (Z)-olefins as selective cyclooxygenase-2 inhibitors.

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References

Citations

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