Identification of a novel 3,5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase |
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Authors: | Thomas Sheela A Li Tongmei Woods Keith W Song Xiaohong Packard Garrick Fischer John P Diebold Robert B Liu Xuesong Shi Yan Klinghofer Vered Johnson Eric F Bouska Jennifer J Olson Amanda Guan Ran Magnone Shayna R Marsh Kennan Luo Yan Rosenberg Saul H Giranda Vincent L Li Qun |
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Affiliation: | Cancer Research, Department R47S, AP10 Abbott Laboratories, 100 Abbott Park Rd, Abbott Park, IL 60064, USA. sheela.thomas@abbott.com |
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Abstract: | Based on lead compounds 2 and 3 a series of 3,5-disubstituted pyridines have been designed and evaluated for inhibition of AKT/PKB. Modifications at the 3 position of the pyridine ring led to a number of potent compounds with improved physical properties, resulting in the identification of 11g as a promising, orally active Akt inhibitor. The synthesis, structure-activity relationship studies, and pharmacokinetic data are presented in this paper. |
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