Potent and selective PKC-θ inhibitors: Advancement from LI to LO

MEDI 368

Anthony S. Prokopowicz III1, Charles L. Cywin1, Georg Dahmann2, Erick R. R. Young1, Ronald L. Magolda1, Mario G. Cardozo1, Derek A. Cogan1, Darren DiSalvo1, John D. Ginn1, Mohammed A. Kashem1, John P. Wolak1, Carol A. Homon1, Thomas M. Farrell1, Heather Grbic1, Hanbo Hu1, Paul V. Kaplita1, Lisa H. Liu1, Denice M. Spero1, Deborah D. Jeanfavre1, Kathy M. O'Shea1, Della M. White1, Joseph M. Woska Jr.1, and Maryanne L. Brown1. (1) Department of Research, Boehringer Ingelheim Pharmaceuticals, Inc, 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877-0368, (2) Department of Medicinal Chemistry, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach an der Riss, D-88397, Germany
An uHTS campaign identified a series of 2,4-diamino-5-nitropyrimidines as potent and selective PKC-θ inhibitors. Hit to lead data is presented showing that we were able to achieve selectivity over multiple kinases, including closely related kinases CDK-1, PLK-1, and PKC-δ. Several highly selective analogues showed cellular potency. The overall profile of this series made it attractive for advancement to lead optimization.

 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007