title: Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors.
abstract: A novel series of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidine-based cyclooxygenase-2 (COX-2) inhibitors, which have a different arrangement of substituents compared to the more common 1,2-diarylheterocycle based molecules, have been discovered. For example, 2-(butyloxy)-4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)pyrimidine (47), a member of the 2-pyrimidinyl ether series, has been shown to be a potent and selective inhibitor with a favourable pharmacokinetic profile, high brain penetration and good efficacy in rat models of hypersensitivity.
authors.affiliation: Pain and Neuroexcitability Discovery Performance Unit, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Swarbrick
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Beswick
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gleave
authors.forename: Richard H
authors.initials: RH
authors.lastname: Green
authors.forename: Sharon
authors.initials: S
authors.lastname: Bingham
authors.forename: Chas
authors.initials: C
authors.lastname: Bountra
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Carter
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Chambers
authors.forename: Iain P
authors.initials: IP
authors.lastname: Chessell
authors.forename: Nick M
authors.initials: NM
authors.lastname: Clayton
authors.forename: Sue D
authors.initials: SD
authors.lastname: Collins
authors.forename: John A
authors.initials: JA
authors.lastname: Corfield
authors.forename: C David
authors.initials: CD
authors.lastname: Hartley
authors.forename: Savvas
authors.initials: S
authors.lastname: Kleanthous
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambeth
authors.forename: Fiona S
authors.initials: FS
authors.lastname: Lucas
authors.forename: Neil
authors.initials: N
authors.lastname: Mathews
authors.forename: Alan
authors.initials: A
authors.lastname: Naylor
authors.forename: Lee W
authors.initials: LW
authors.lastname: Page
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Payne
authors.forename: Neil A
authors.initials: NA
authors.lastname: Pegg
authors.forename: Helen S
authors.initials: HS
authors.lastname: Price
authors.forename: John
authors.initials: J
authors.lastname: Skidmore
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stevens
authors.forename: Richard
authors.initials: R
authors.lastname: Stocker
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Stratton
authors.forename: Alastair J
authors.initials: AJ
authors.lastname: Stuart
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Wiseman
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D051546:Cyclooxygenase 2 / Q000737:chemistry; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004195:Disease Models, Animal; D015195:Drug Design; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000588:Amines; D052246:Cyclooxygenase 2 Inhibitors; D004987:Ethers; D011743:Pyrimidines; D013450:Sulfones; D051546:Cyclooxygenase 2