Design and synthesis of benzoazepin-2-one analogs as allosteric binders targeting the PIF pocket of PDK1

L Wei, X Gao, R Warne, X Hao, D Bussiere, X Gu…

Index: Wei, Linyi; Gao, Xiaoqi; Warne, Robert; Hao, Xueshi; Bussiere, Dirksen; Gu, Xiang-Ju; Uno, Tetsuo; Liu, Yi Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 13 p. 3897 - 3902

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Citation Number: 21

Abstract

A novel series of benzoazepin-2-ones were designed and synthesized targeting the PIF pocket of AGC protein kinases, among which a series of thioether-linked benzoazepin-2- ones were discovered to bind to the PIF pocket of 3-phosphoinositide-dependent kinase-1 (PDK1), and to displace the PIF peptide with an EC50 values in the lower micromolar range. The structure–activity relationships (SARs) of the linker region, tail region, and distal ...