Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, Medicines Research Centre, Via A Fleming 4, 37135 Verona, Italy.
Bioorg Med Chem Lett. 2011 Jan 1;21(1):602-5. doi: 10.1016/j.bmcl.2010.09.025. Epub 2010 Sep 15.
Two complementary stereospecific synthetic approaches for the preparation of unsymmetrical ortho-substituted N-(4,4-diphenylbut-3-enyl) derivatives of nipecotic acid are described. Determination of the activity of the prepared compounds at the GAT-1 transporter highlighted differing SAR requirements of the E- and Z-phenyl rings, and led to the discovery of a compound with comparable potency to tiagabine. Some attempts to replace nipecotic acid with alternative novel amino acids are also described.
两种互补的立体化学方法用于制备非对称邻位取代的 N-(4,4-二苯基丁-3-烯基)哌啶酸衍生物。研究了制备的化合物在 GAT-1 转运体上的活性，突出了 E-和 Z-苯基环的不同 SAR 要求，并发现了一种与噻加宾具有相当效力的化合物。还描述了一些用替代的新型氨基酸替代哌啶酸的尝试。
