Bioorganic & Medicinal Chemistry Letters 2012-04-15

2-anilino-4-aryl-8H-purine derivatives as inhibitors of PDK1.

Stéphanie Blanchard, Chang Kai Soh, Chai Ping Lee, Anders Poulsen, Zahid Bonday, Kay Lin Goh, Kee Chuan Goh, Miah Kiat Goh, Mohammed Khalid Pasha, Haishan Wang, Meredith Williams, Jeanette M Wood, Kantharaj Ethirajulu, Brian W Dymock

Index: Bioorg. Med. Chem. Lett. 8th ed., 22 , 2880-2884, (2012)

Full Text: HTML

Abstract

A series of 2-anilino substituted 4-aryl-8H-purines were prepared as potent inhibitors of PDK1, a serine-threonine kinase thought to play a role in the PI3K/Akt signaling pathway, a key mediator of cancer cell growth, survival and tumorigenesis. The synthesis, SAR and ADME properties of this series of compounds are discussed culminating in the discovery of compound 6 which possessed sub-micromolar cell proliferation activity and 65% oral bioavailability in mice.Copyright © 2012 Elsevier Ltd. All rights reserved.