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

Imadul Islam; Judi Bryant; Yuo-Ling Chou; Monica J Kochanny; Wheeseong Lee; Gary B Phillips; Hongyi Yu; Marc Adler; Marc Whitlow; Elena Ho; Dao Lentz; Mark A Polokoff; Babu Subramanyam; James M Wu; Daguang Zhu; Richard I Feldman; Damian O Arnaiz

doi:10.1016/j.bmcl.2007.04.071

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.

Authors

Imadul Islam¹, Judi Bryant, Yuo-Ling Chou, Monica J Kochanny, Wheeseong Lee, Gary B Phillips, Hongyi Yu, Marc Adler, Marc Whitlow, Elena Ho, Dao Lentz, Mark A Polokoff, Babu Subramanyam, James M Wu, Daguang Zhu, Richard I Feldman, Damian O Arnaiz

Affiliation

¹ Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA.

PMID: 17531483
DOI: 10.1016/j.bmcl.2007.04.071

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