Design and synthesis of (E)-1,1,2-triarylethenes: novel inhibitors of the cyclooxygenase-2 (COX-2) isozyme.
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.
Uddin
Md Jashim
MJ
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
Rao
P N Praveen
PN
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; D015195:Drug Design; D005030:Ethylenes / Q000138:chemical synthesis* / Q000494:pharmacology; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012756:Sheep; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005030:Ethylenes; D006841:Hydrocarbons, Aromatic; D007527:Isoenzymes; C036216:ethylene; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases