title: Design and synthesis of (E)-1,1,2-triarylethenes: novel inhibitors of the cyclooxygenase-2 (COX-2) isozyme.
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.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada T6G 2N8.
authors.forename: Md Jashim
authors.initials: MJ
authors.lastname: Uddin
authors.forename: P N Praveen
authors.initials: PN
authors.lastname: Rao
authors.forename: Robert
authors.initials: R
authors.lastname: McDonald
authors.forename: Edward E
authors.initials: EE
authors.lastname: Knaus
mesh_terms: 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
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005030:Ethylenes; D006841:Hydrocarbons, Aromatic; D007527:Isoenzymes; C036216:ethylene; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases