Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation |
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| Authors: | John J. Parlow Mary W. Burney Brenda L. Case Thomas J. Girard Kerri A. Hall Ronald R. Hiebsch Rita M. Huff Rhonda M. Lachance Deborah A. Mischke Stephen R. Rapp Rhonda S. Woerndle Michael D. Ennis |
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| Affiliation: | 1. Department of Medicinal Chemistry, Pfizer Global Research and Development, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA;2. Department of Biology, Pfizer Global Research and Development, 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA |
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| Abstract: | 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. |
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