1. Academic Validation
  2. Discovery of potent and selective PKC-theta inhibitors

Discovery of potent and selective PKC-theta inhibitors

  • Bioorg Med Chem Lett. 2007 Jan 1;17(1):225-30. doi: 10.1016/j.bmcl.2006.09.056.
Charles L Cywin 1 Georg Dahmann Anthony S Prokopowicz 3rd Erick R R Young Ronald L Magolda Mario G Cardozo Derek A Cogan Darren Disalvo John D Ginn Mohammed A Kashem John P Wolak Carol A Homon Thomas M Farrell Heather Grbic Hanbo Hu Paul V Kaplita Lisa H Liu Denice M Spero Deborah D Jeanfavre Kathy M O'Shea Della M White Joseph R Woska Jr Maryanne L Brown
Affiliations

Affiliation

  • 1 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.

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