Optimization of 2-phenyl-pyrimidine-4-carboxamides towards potent, orally bioavailable and selective P2Y12 antagonists for inhibition of platelet aggregation

2-Phenyl-pyrimidine-4-carboxamide analogs were identified as P2Y(12) antagonists. Optimization of the carbon-linked or nitrogen-linked substituent at the 6-position of the pyrimidine ring provided compounds with excellent ex vivo potency in the platelet aggregation assay in human plasma. Compound 23u met the objectives for activity, selectivity and ADMET properties. (C) 2014 Elsevier Ltd. All rights reserved.