Discovery of trans-3, 4′-bispyridinylethylenes as potent and novel inhibitors of protein kinase B (PKB/Akt) for the treatment of cancer: synthesis and biological …

…, GD Zhu, J Gong, A Claibone, C Dalton, Y Luo…

Index: Li, Qun; Li, Tongmei; Zhu, Gui-Dong; Gong, Jianchun; Claibone, Akiyo; Dalton, Chris; Luo, Yan; Johnson, Eric F.; Shi, Yan; Liu, Xuesong; Klinghofer, Vered; Bauch, Joy L.; Marsh, Kennan C.; Bouska, Jennifer J.; Arries, Shannon; De Jong, Ron; Oltersdorf, Tilman; Stoll, Vincent S.; Jakob, Clarissa G.; Rosenberg, Saul H.; Giranda, Vincent L. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 6 p. 1679 - 1685

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Citation Number: 36

Abstract

A novel series of Akt/PKB inhibitors derived from a screening lead (1) has been prepared. The novel trans-3, 4′-bispyridinylethylenes described herein are potent inhibitors of Akt/PKB with IC50 values in the low double-digit nanomolar range against Akt1. Compound 2q shows excellent selectivity against distinct families of kinases such as tyrosine kinases and CAMK, and displays poor to modest selectivity against closely related kinases in the ...