2. Academic Validation
  3. Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors

Identification of [4-[4-(methylsulfonyl)phenyl]-6-(trifluoromethyl)-2-pyrimidinyl] amines and ethers as potent and selective cyclooxygenase-2 inhibitors

  • Bioorg Med Chem Lett. 2009 Aug 1;19(15):4504-8. doi: 10.1016/j.bmcl.2009.02.085.
Martin E Swarbrick 1,  Paul J Beswick,  Robert J Gleave,  Richard H Green,  Sharon Bingham,  Chas Bountra,  Malcolm C Carter,  Laura J Chambers,  Iain P Chessell,  Nick M Clayton,  Sue D Collins,  John A Corfield,  C David Hartley,  Savvas Kleanthous,  Paul F Lambeth,  Fiona S Lucas,  Neil Mathews,  Alan Naylor,  Lee W Page,  Jeremy J Payne,  Neil A Pegg,  Helen S Price,  John Skidmore,  Alexander J Stevens,  Richard Stocker,  Sharon C Stratton,  Alastair J Stuart,  Joanne O Wiseman
Affiliations

Affiliation

  • 1 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.
PMID: 19520573 DOI: 10.1016/j.bmcl.2009.02.085
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.

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