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
em 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
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzofuranos
/
Proteínas Serina-Treonina Quinases
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Peptídeos e Proteínas de Sinalização Intracelular
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Inibidores de Proteínas Quinases
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Inibidores de Fosfoinositídeo-3 Quinase
Limite:
Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article