Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened
ACS Medicinal Chemistry Letters2011Vol. 3(2), pp. 106–111
Citations Over TimeTop 11% of 2011 papers
Michael J. Munchhof, Qifang Li, Andrei Shavnya, Gary Borzillo, Tracey Boyden, Christopher S. Jones, Susan LaGreca, Luis Martinez-Alsina, Nandini C. Patel, Kathleen Pelletier, Larry A. Reiter, Michael Robbins, George T. Tkalcevic
Abstract
Inhibitors of the Hedgehog signaling pathway have generated a great deal of interest in the oncology area due to the mounting evidence of their potential to provide promising therapeutic options for patients. Herein, we describe the discovery strategy to overcome the issues inherent in lead structure 1 that resulted in the identification of Smoothened inhibitor 1-((2R,4R)-2-(1H-benzo[d]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea (PF-04449913, 26), which has been advanced to human clinical studies.
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