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ID: ALA1156904

Journal: Bioorg Med Chem Lett

Title: Part II: piperazinyl-glutamate-pyridines as potent orally bioavailable P2Y12 antagonists for inhibition of platelet aggregation.

Authors: Parlow JJ, Burney MW, Case BL, Girard TJ, Hall KA, Harris PK, Hiebsch RR, Huff RM, Lachance RM, Mischke DA, Rapp SR, Woerndle RS, Ennis MD.

Abstract: 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.

CiteXplore: 20097563

DOI: 10.1016/j.bmcl.2009.12.110