Discovery of spirocyclic sulfonamides as potent Akt inhibitors with exquisite selectivity against PKA

We describe the design and synthesis of novel bicyclic spiro sulfonamides as potent Akt inhibitors. Through structure-based rational design, we have successfully improved PKA selectivity of previously disclosed spirochromanes. Representative compounds showed favorable Akt potency while exhibiting up to 1000-fold selectivity against PKA. (C) 2011 Elsevier Ltd. All rights reserved.