Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1363733 | Bioorganic & Medicinal Chemistry Letters | 2009 | 4 Pages |
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 compounds 26 and 27 as highly potent inhibitors (Ki <1 nM) of p70S6K, with >100-fold selectivity against PKA, ROCK and GSK3.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Upul Bandarage, Brian Hare, Jonathan Parsons, Ly Pham, Craig Marhefka, Guy Bemis, Qing Tang, Cameron Stuver Moody, Steve Rodems, Sundeep Shah, Chris Adams, Jose Bravo, Emmanuelle Charonnet, Vladimir Savic, Jon H. Come, Jeremy Green,