| 19796941 |
Parlow JJ, Burney MW, Case BL, Girard TJ, Hall KA, Hiebsch RR, Huff RM, Lachance RM, Mischke DA, Rapp SR, Woerndle RS, Ennis MD: Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation. Bioorg Med Chem Lett. 2009 Nov 1;19(21):6148-56. 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. |
32(0,1,1,2) |