Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373299 | Bioorganic & Medicinal Chemistry Letters | 2009 | 7 Pages |
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 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 22J with good human PRP potency, selectivity, in vivo efficacy and oral bioavailability.
Graphical abstractPolymer-assisted solution-phase (PASP) parallel library synthesis was used to discover piperazinyl-glutamate-pyridines as P2Y12 antagonists. Optimization led to compound 22J, an orally bioavailable, direct acting, reversible P2Y12 antagonist.Figure optionsDownload full-size imageDownload as PowerPoint slide