Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: Optimization of BX-517

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.