Swarbrick Martin E, Beswick Paul J, Gleave Robert J, Green Richard H, Bingham Sharon, Bountra Chas, Carter Malcolm C, Chambers Laura J, Chessell Iain P, Clayton Nick M, Collins Sue D, Corfield John A, Hartley C David, Kleanthous Savvas, Lambeth Paul F, Lucas Fiona S, Mathews Neil, Naylor Alan, Page Lee W, Payne Jeremy J, Pegg Neil A, Price Helen S, Skidmore John, Stevens Alexander J, Stocker Richard, Stratton Sharon C, Stuart Alastair J, Wiseman Joanne O
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.
Bioorg Med Chem Lett. 2009 Aug 1;19(15):4504-8. doi: 10.1016/j.bmcl.2009.02.085. Epub 2009 Feb 26.
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.
已发现一系列新型的基于[4-[4-(甲基磺酰基)苯基]-6-(三氟甲基)-2-嘧啶]的环氧化酶-2（COX-2）抑制剂，与更常见的基于1,2-二芳基杂环的分子相比，其取代基排列不同。例如，2-(丁氧基)-4-[4-(甲基磺酰基)苯基]-6-(三氟甲基)嘧啶（47），属于2-嘧啶基醚系列，已被证明是一种强效且选择性的抑制剂，具有良好的药代动力学特征、高脑渗透性以及在大鼠过敏模型中的良好疗效。
