Checkpoint kinase inhibitors: SAR and radioprotective properties of a series of 2-arylbenzimidazoles

…, CR Pandit, L Karlsson, JG Breitenbucher

Index: Arienti, Kristen L.; Brunmark, Anders; Axe, Frank U.; McClure, Kelly; Lee, Alice; Blevitt, Jon; Neff, Danielle K.; Huang, Liming; Crawford, Shelby; Pandit, Chennagiri R.; Karlsson, Lars; Breitenbucher, J. Guy Journal of Medicinal Chemistry, 2005 , vol. 48, # 6 p. 1873 - 1885

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Citation Number: 133

Abstract

The discovery of a series of novel, potent, and highly selective inhibitors of the DNA damage control kinase chk2 is disclosed. Here we report the first SAR study around inhibitors of this kinase. High-throughput screening of purified human chk2 led to the identification of a novel series of 2-arylbenzimidazole inhibitors of the kinase. Optimization was facilitated using homology models of chk2 and docking of inhibitors, leading to the highly potent 2- ...