Discovery of potent and selective PKC-θ inhibitors
…, G Dahmann, AS Prokopowicz, ERR Young…
文献索引：Cywin, Charles L.; Dahmann, Georg; Prokopowicz III, Anthony S.; Young, Erick R.R.; Magolda, Ronald L.; Cardozo, Mario G.; Cogan, Derek A.; DiSalvo, Darren; Ginn, John D.; Kashem, Mohammed A.; Wolak, John P.; Homon, Carol A.; Farrell, Thomas M.; Grbic, Heather; Hu, Hanbo; Kaplita, Paul V.; Liu, Lisa H.; Spero, Denice M.; Jeanfavre, Deborah D.; O'Shea, Kathy M.; White, Della M.; Woska Jr., Joseph R.; Brown, Maryanne L. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 1 p. 225 - 230
An uHTS campaign was performed to identify selective inhibitors of PKC-θ. 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-θ 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. ...
