title: 4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2).
abstract: A series of methysulfonyl or sulfonamido substituted 4,5-diaryloxazole were prepared and evaluated for their ability to inhibit the inducible form of cyclooxygenase (COX-2) in vitro and in vivo. Several unique substitution patterns were identified that led to potent and selective inhibitors of COX-2. In general, 2-trifluoromethly-4,5-diaryloxazoles substituted with a methylsulfonyl or sulfonamido group were particularly potent inhibitors. One of the more potent compounds with a selectivity for COX-2 of about 800 fold was 4b (SC-299). SC-299, a highly fluorescent molecule, may be useful for spectroscopic studies on preferential inhibitor binding to COX-2.
authors.affiliation: Department of Medicinal Chemistry, G.D.Searle/Monsanto Company, St. Louis, MO 63198, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Talley
authors.forename: S R
authors.initials: SR
authors.lastname: Bertenshaw
authors.forename: D L
authors.initials: DL
authors.lastname: Brown
authors.forename: J S
authors.initials: JS
authors.lastname: Carter
authors.forename: M J
authors.initials: MJ
authors.lastname: Graneto
authors.forename: C M
authors.initials: CM
authors.lastname: Koboldt
authors.forename: J L
authors.initials: JL
authors.lastname: Masferrer
authors.forename: B H
authors.initials: BH
authors.lastname: Norman
authors.forename: D J
authors.initials: DJ
authors.lastname: Rogier
authors.forename: B S
authors.initials: BS
authors.lastname: Zwwifel
authors.forename: K
authors.initials: K
authors.lastname: Seibert
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects*; D008565:Membrane Proteins; D010080:Oxazoles / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010080:Oxazoles; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases