Department of Medicinal Chemistry, Pfizer Global Research and Development, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6148-56. doi: 10.1016/j.bmcl.2009.09.017. Epub 2009 Sep 10.
Piperazinyl-glutamate-pyrimidines were prepared with oxygen, nitrogen, and sulfur substitution at the 4-position of the pyrimidine leading to highly potent P2Y12 antagonists. In particular, 4-substituted piperidine-4-pyrimidines provided compounds with exceptional potency. Pharmacokinetic and physicochemical properties were fine-tuned through modifications at the 4-position of the piperidine ring leading to compounds with good human PRP potency, selectivity, clearance and oral bioavailability.
哌嗪基-谷氨酸-嘧啶类化合物经氧、氮和硫取代嘧啶的 4 位，得到了高活性的 P2Y12 拮抗剂。特别是，4-取代的哌啶-4-嘧啶类化合物提供了具有卓越活性的化合物。通过对哌啶环 4 位的修饰，调整了化合物的药代动力学和物理化学性质，得到了具有良好人血小板聚集抑制活性、选择性、清除率和口服生物利用度的化合物。
