4-(Benzimidazol-2-yl)-1, 2, 5-oxadiazol-3-ylamine derivatives: potent and selective p70S6 kinase inhibitors

U Bandarage, B Hare, J Parsons, L Pham…

Index: Bandarage, Upul; Hare, Brian; Parsons, Jonathan; Pham, Ly; Marhefka, Craig; Bemis, Guy; Tang, Qing; Moody, Cameron Stuver; Rodems, Steve; Shah, Sundeep; Adams, Chris; Bravo, Jose; Charonnet, Emmanuelle; Savic, Vladimir; Come, Jon H.; Green, Jeremy Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 17 p. 5191 - 5194

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Citation Number: 17

Abstract

We report herein the design and synthesis of 4-(benzimidazol-2-yl)-1, 2, 5-oxadiazol-3- amine derivatives as inhibitors of p70S6 kinase. Screening hits containing the 4- (benzimidazol-2-yl)-1, 2, 5-oxadiazol-3-ylamine scaffold were optimized for p70S6K potency and selectivity against related kinases. Structure-based design employing an active site homology model derived from PKA led to the preparation of benzimidazole 5-substituted ...