Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517
- Bioorg Med Chem Lett. 2007 Jul 15;17(14):3819-25. doi: 10.1016/j.bmcl.2007.05.060.
- 1. Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA. [email protected]
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.