1188276-02-9Relevant articles and documents
Piperazinyl glutamate pyridines as potent orally bioavailable P2Y 12 antagonists for inhibition of platelet aggregation
Parlow, John J.,Burney, Mary W.,Case, Brenda L.,Girard, Thomas J.,Hall, Kerri A.,Harris, Peter K.,Hiebsch, Ronald R.,Huff, Rita M.,Lachance, Rhonda M.,Mischke, Deborah A.,Rapp, Stephen R.,Woerndle, Rhonda S.,Ennis, Michael D.
experimental part, p. 2010 - 2037 (2010/07/08)
Polymer-assisted solution-phase (PASP) parallel library synthesis was used to discover a piperazinyl glutamate pyridine as a P2Y12 antagonist. Exploitation of this lead provided compounds with excellent inhibition of platelet aggregation as measured in a human platelet rich plasma (PRP) assay. Pharmacokinetic and physiochemical properties were optimized through modifications at the 4-position of the pyridine ring and the terminal nitrogen of the piperazine ring, leading to compound (4S)-4-[({4-[4-(methoxymethyl) piperidin-1-yl]-6-phenylpyridin-2-yl}carbonyl)amino]-5-oxo-5-{4-[(pentyloxy) carbonyl]piperazin-1-yl}pentanoic acid 47s with good human PRP potency, selectivity, in vivo efficacy, and oral bioavailability. Compound 47s was selected for further preclinical evaluations.
