Novel benzofuran-3-one indole inhibitors of PI3 kinase-alpha and the mammalian target of rapamycin: hit to lead studies.
Bioorg Med Chem Lett
; 20(8): 2586-90, 2010 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-20303263
ABSTRACT
A series of benzofuran-3-one indole phosphatidylinositol-3-kinases (PI3K) inhibitors identified via HTS has been prepared. The optimized inhibitors possess single digit nanomolar activity against p110alpha (PI3K-alpha), good pharmaceutical properties, selectivity versus p110gamma (PI3K-gamma), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-alpha and mTOR supports the proposed rationale for selectivity. Compounds show activity in multiple cellular proliferation assays with signaling through the PI3K pathway confirmed via phospho-Akt inhibition in PC-3 cells.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benzofuranos
/
Proteínas Serina-Treonina Quinasas
/
Péptidos y Proteínas de Señalización Intracelular
/
Inhibidores de Proteínas Quinasas
/
Inhibidores de las Quinasa Fosfoinosítidos-3
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Estados Unidos