A new class of acyclic 2-alkyl-1,2-diaryl (E)-olefins as selective cyclooxygenase-2 (COX-2) inhibitors.
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.
Uddin
Md Jashim
MJ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.
Rao
P N Praveen
PN
Rahim
Md Abdur
MA
McDonald
Robert
R
Knaus
Edward E
EE
D000818:Animals; D001665:Binding Sites; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases