Piperazinyl-glutamate-pyrimidines as potent P2Y12 antagonists for inhibition of platelet aggregation |
| |
| 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 |
| |
| Institution: | 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 |
| |
| 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. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
