Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Harlow, Essex, UK.
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4683-8. doi: 10.1016/j.bmcl.2010.05.026. Epub 2010 May 31.
Optimization of the novel alpha-2-delta-1 ligand 4 provided compounds 37 and 38 which have improved DMPK profiles, good in vivo analgesic activity and in vitro selectivity over alpha-2-delta-2. An in-house P-gp prediction programme and the MetaSite software package were used to help solve the specific problems of high P-gp efflux and high in vivo clearance.
新型 alpha-2-delta-1 配体 4 的优化提供了化合物 37 和 38，它们具有改善的 DMPK 特征、良好的体内镇痛活性和体外对 alpha-2-delta-2 的选择性。内部的 P-糖蛋白预测程序和 MetaSite 软件包被用于帮助解决高 P-糖蛋白外排和高体内清除率的具体问题。
