6-[(5-氯-2-{[(4-氯-2-氟苯基)甲基]氧基}苯基)甲基]-2-吡啶羧酸酯（GSK269984A）的发现，一种用于治疗炎性疼痛的EP(1)受体拮抗剂。
Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.
作者信息
Hall Adrian, Billinton Andy, Brown Susan H, Chowdhury Anita, Clayton Nicholas M, Giblin Gerard M P, Gibson Mairi, Goldsmith Paul A, Hurst David N, Naylor Alan, Peet Caroline F, Scoccitti Tiziana, Wilson Alexander W, Winchester Wendy
机构信息
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.
出版信息
Bioorg Med Chem Lett. 2009 May 1;19(9):2599-603. doi: 10.1016/j.bmcl.2009.02.112. Epub 2009 Mar 3.
We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.
我们描述了导致鉴定出EP(1)受体拮抗剂GSK269984A（8h）的药物化学项目。GSK269984A的设计旨在克服先前的EP(1)拮抗剂（如GW848687X）所遇到的研发问题，并且发现在炎性疼痛的临床前模型中具有优异的活性。然而，在进行跨物种药代动力学分析时，预测GSK269984A在人体中的药代动力学不理想，因此推进到人体微剂量研究阶段。
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