第二部分：哌嗪基谷氨酸吡啶作为有效的口服生物利用度 P2Y12 拮抗剂，用于抑制血小板聚集。
Part II: piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation.
机构信息
Department of Medicinal Chemistry, Pfizer Global Research & Development, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA.
出版信息
Bioorg Med Chem Lett. 2010 Feb 15;20(4):1388-94. doi: 10.1016/j.bmcl.2009.12.110. Epub 2010 Jan 4.
Efforts to refine the SAR of the piperazinyl-glutamate-pyridines for more potent analogs with improved pharmacokinetic profiles are described. Exploring substituted piperidines and other ring systems at the 4-pyridyl position led to compounds with improved potency and pharmacokinetic properties over candidate I. In particular, compounds 4t and 5t were discovered with a 10-fold improvement over potency and improved pharmacokinetic profiles in both the rat and dog.
本文描述了为获得具有更好药代动力学特征的更有效类似物而对哌嗪基谷氨酸吡啶的 SAR 进行精细化研究的努力。在 4-吡啶基位置探索取代的哌啶和其他环系，得到了比候选物 I 具有更高活性和更好药代动力学性质的化合物。特别是，化合物 4t 和 5t 的活性提高了 10 倍，在大鼠和狗中的药代动力学特征也得到了改善。
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