Novel benzofuran-3-one indole inhibitors of PI3 kinase-α and the mammalian target of rapamycin: Hit to lead studies

…, N Brooijmans, L Feldberg, I Hollander, S Kim…

Index: Bursavich, Matthew G.; Brooijmans, Natasja; Feldberg, Lawrence; Hollander, Irwin; Kim, Stephen; Lombardi, Sabrina; Park, Kaapjoo; Mallon, Robert; Gilbert, Adam M. Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 8 p. 2586 - 2590

Full Text: HTML

Citation Number: 24

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 p110α (PI3K-α), good pharmaceutical properties, selectivity versus p110γ (PI3K-γ), and tunable selectivity versus the mammalian target of rapamycin (mTOR). Modeling of compounds 9 and 32 in homology models of PI3K-α and mTOR ...