Discovery of PF-04449913, a potent and orally bioavailable inhibitor of smoothened
MJ Munchhof, Q Li, A Shavnya… - ACS medicinal …, 2012 - ACS Publications
MJ Munchhof, Q Li, A Shavnya, GV Borzillo, TL Boyden, CS Jones, SD LaGreca…
ACS medicinal chemistry letters, 2012•ACS PublicationsInhibitors 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-((2 R, 4 R)-2-(1 H-benzo [d] imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl) urea
(PF-04449913, 26), which has been advanced to human clinical studies.
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-((2 R, 4 R)-2-(1 H-benzo [d] imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl) urea
(PF-04449913, 26), which has been advanced to human clinical studies.
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.
ACS Publications