A new class of acyclic 2-alkyl-1,2-diaryl (E)-olefins as selective cyclooxygenase-2 (COX-2) inhibitors

Md Jashim Uddin; P N Praveen Rao; Md Abdur Rahim; Robert McDonald; Edward E Knaus

doi:10.1016/j.bmcl.2004.07.027

A new class of acyclic 2-alkyl-1,2-diaryl (E)-olefins as selective cyclooxygenase-2 (COX-2) inhibitors

Bioorg Med Chem Lett. 2004 Oct 4;14(19):4911-4. doi: 10.1016/j.bmcl.2004.07.027.

Authors

Md Jashim Uddin¹, P N Praveen Rao, Md Abdur Rahim, Robert McDonald, Edward E Knaus

Affiliation

¹ Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.

PMID: 15341950
DOI: 10.1016/j.bmcl.2004.07.027

Abstract

A new class of (E)-2-alkyl-2-(4-methanesulfonylphenyl)-1-phenylethenes were designed for evaluation as selective cyclooxygense-2 (COX-2) inhibitors. The target olefins were synthesized, via a Takeda olefination reaction, followed by oxidation of the respective thiomethyl olefinic intermediate. In vitro COX-1/COX-2 inhibition studies identified (E)-2-(4-methanesulfonylphenyl)-1-phenyloct-1-ene (8d) as a potent (IC(50)=0.77 microM) and selective (Selectivity Index>130) COX-2 inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Binding Sites
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Cyclooxygenase Inhibitors / pharmacology
Mice
Models, Molecular
Prostaglandin-Endoperoxide Synthases / chemistry
Structure-Activity Relationship

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases