title: Terphenyl cyclooxygenase-2 (COX-2) inhibitors: optimization of the central ring and o-biphenyl analogs.
abstract: The discovery of terphenyl derivatives as highly selective COX-2 inhibitors resulted from our efforts to overcome poor pharmacokinetics demonstrated by the COX-2 selective diarylthiophene DuP 697 [2-bromo-4-(4'-sulfonylmethyl)phenyl-5-(4'-fluoro)phenylthiophe ne]. Detailed SAR related to the ortho-biphenyls and variants of the central ring are described herein.
authors.affiliation: The DuPont Pharmaceutical Company, Wilmington, DE 19880-0500, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Pinto
authors.forename: D G
authors.initials: DG
authors.lastname: Batt
authors.forename: W J
authors.initials: WJ
authors.lastname: Pitts
authors.forename: J J
authors.initials: JJ
authors.lastname: Petraitis
authors.forename: M J
authors.initials: MJ
authors.lastname: Orwat
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: J W
authors.initials: JW
authors.lastname: Jetter
authors.forename: S R
authors.initials: SR
authors.lastname: Sherk
authors.forename: G C
authors.initials: GC
authors.lastname: Houghton
authors.forename: R A
authors.initials: RA
authors.lastname: Copeland
authors.forename: M B
authors.initials: MB
authors.lastname: Covington
authors.forename: J M
authors.initials: JM
authors.lastname: Trzaskos
authors.forename: R L
authors.initials: RL
authors.lastname: Magolda
mesh_terms: D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000187:drug effects; D015394:Molecular Structure; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000493:pharmacokinetics
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D013876:Thiophenes; C064874:DuP 697; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases