2. Academic Validation
  3. 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. [email protected]
PMID: 17055721 DOI: 10.1016/j.bmcl.2006.09.056
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.

Figures
Products