Structural highlights
Publication Abstract from PubMed
Optimization of AZD6482 (2), the first antiplatelet PI3Kbeta inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3Kalpha to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kbeta inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kbeta inhibitors, useful as antiplatelet agents.,Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T Bioorg Med Chem Lett. 2014 Aug 15;24(16):3936-43. doi:, 10.1016/j.bmcl.2014.07.007. Epub 2014 Jul 9. PMID:25042253[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Giordanetto F, Barlaam B, Berglund S, Edman K, Karlsson O, Lindberg J, Nylander S, Inghardt T. Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kbeta inhibitors, useful as antiplatelet agents. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3936-43. doi:, 10.1016/j.bmcl.2014.07.007. Epub 2014 Jul 9. PMID:25042253 doi:http://dx.doi.org/10.1016/j.bmcl.2014.07.007
