Design of acyclic triaryl olefins: a new class of potent and selective cyclooxygenase-2 (COX-2) inhibitors.
A new class of acyclic 1,1-diphenyl-2-(4-methylsulfonylphenyl)-2-alkyl-1-ethenes were synthesized, via a short two-step McMurry olefination reaction and then oxidation of the thiomethyl intermediate using Oxone, in 62-76% yield. The title compounds possess identical C-1 phenyl substituents which precludes the possibility of (Z)- and (E)-stereoisomers. 1,1-Diphenyl-2-(4-methylsulfonylphenyl)hex-1-ene exhibited highly potent (IC(50)=0.014 microM) and selective COX-2 (Selectivity Index >7142) inhibitory activity.
Uddin
Md Jashim
MJ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
Rao
P N Praveen
PN
Knaus
Edward E
EE
D000475:Alkenes / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology; D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology; D015195:Drug Design; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D011451:Prostaglandin-Endoperoxide Synthases; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000475:Alkenes; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases