Design and synthesis of (E)-1,1,2-triarylethenes: novel inhibitors of the cyclooxygenase-2 (COX-2) isozyme

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

doi:10.1016/j.bmcl.2004.10.050

Design and synthesis of (E)-1,1,2-triarylethenes: novel inhibitors of the cyclooxygenase-2 (COX-2) isozyme

Bioorg Med Chem Lett. 2005 Jan 17;15(2):439-42. doi: 10.1016/j.bmcl.2004.10.050.

Authors

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

Affiliation

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

PMID: 15603969
DOI: 10.1016/j.bmcl.2004.10.050

Abstract

A novel class of acyclic 1,1,2-triaryl (E)-ethenes was designed that were synthesized via an (E)-selective Takeda olefination reaction. Among the group of compounds evaluated, (E)-2-(4-fluorophenyl)-1-(4-methylsulfonylphenyl)-1-phenylethene (10c) emerged as the most potent (COX-2 IC(50)=0.0316 microM), and selective (selectivity index>3164), 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
Drug Design
Ethylenes / chemical synthesis*
Ethylenes / pharmacology
Hydrocarbons, Aromatic / chemistry*
Inhibitory Concentration 50
Isoenzymes / antagonists & inhibitors*
Molecular Conformation
Prostaglandin-Endoperoxide Synthases / metabolism*
Sheep
Stereoisomerism
Structure-Activity Relationship

Substances

Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Ethylenes
Hydrocarbons, Aromatic
Isoenzymes
ethylene
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases