Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kß inhibitors, useful as antiplatelet agents.
Bioorg Med Chem Lett
; 24(16): 3936-43, 2014 Aug 15.
Article
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| MEDLINE
| ID: mdl-25042253
ABSTRACT
Optimization of AZD6482 (2), the first antiplatelet PI3Kß 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 PI3Kα to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3Kß inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Agregación Plaquetaria
/
Inhibidores de Proteínas Quinasas
/
Descubrimiento de Drogas
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Inhibidores de las Quinasa Fosfoinosítidos-3
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article