Boehringer Ingelheim Pharmaceuticals, Inc., Department of Medicinal Chemistry, 900 Ridgebury Road, Ridgefield, CT 06877-0368, USA. ccywin@rdg.boehringer-ingelheim.com
Abstract:
An uHTS campaign was performed to identify selective inhibitors of PKC-theta. Initial triaging of the hit set based on selectivity and historical analysis led to the identification of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-theta inhibitors. A homology model and initial SAR is presented demonstrating that a 2-arylalkylamino substituent in conjunction with suitable 4-diamino substituent are essential for achieving selectivity over many kinases. Additional hit to lead profiling is presented on selected compounds.