Abstract
Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.
MeSH terms
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3-Phosphoinositide-Dependent Protein Kinases
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Cell Line, Tumor
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Humans
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Indoles / chemistry*
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Indoles / pharmacology
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Protein Kinase Inhibitors / chemistry
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Protein Kinase Inhibitors / pharmacology*
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Protein Serine-Threonine Kinases / antagonists & inhibitors*
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Urea / analogs & derivatives*
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Urea / chemistry
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Urea / pharmacology
Substances
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BX 517
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Indoles
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Protein Kinase Inhibitors
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Urea
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3-Phosphoinositide-Dependent Protein Kinases
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PDPK1 protein, human
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Protein Serine-Threonine Kinases