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

Back

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

Journal article

Peer reviewed

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, …

Bioorganic & medicinal chemistry letters, Vol.17(14), pp.3814-3818

15/07/2007

DOI: https://doi.org/10.1016/j.bmcl.2007.04.071

PMID: 17531483

Abstract

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

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.

Metrics

1 Record Views

See more details

Details

Title: Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: design, synthesis and biological activity
Creators - without role: Imadul Islam - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Judi Bryant - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Yuo-Ling Chou - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Monica J Kochanny
Wheeseong Lee - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Gary B Phillips - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Hongyi Yu - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Marc Adler - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Marc Whitlow - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Elena Ho - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Dao Lentz - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Mark A Polokoff - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Babu Subramanyam - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
James M Wu
Daguang Zhu - Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA
Richard I Feldman
Damian O Arnaiz
Publication Details: Bioorganic & medicinal chemistry letters, Vol.17(14), pp.3814-3818
Identifiers: 9921171508331
Academic Unit: King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article