Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3814-8. doi: 10.1016/j.bmcl.2007.04.071. Epub 2007 Apr 27.

Abstract

HTS screening identified 1 with micromolar inhibitory activity against PDK1. Optimization of 1 afforded 4i (BX-517) which has single-digit nanomolar activity against PDK1 and excellent selectivity against PKA.

MeSH terms

  • 3-Phosphoinositide-Dependent Protein Kinases
  • Drug Design
  • Indoles / chemistry*
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors*

Substances

  • Indoles
  • Protein Kinase Inhibitors
  • 3-Phosphoinositide-Dependent Protein Kinases
  • Protein-Serine-Threonine Kinases