1 research outputs found
Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened
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 <b>1</b> that resulted in the identification
of Smoothened inhibitor 1-((2<i>R</i>,4<i>R</i>)-2-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)-1-methylpiperidin-4-yl)-3-(4-cyanophenyl)urea
(PF-04449913, <b>26</b>), which has been advanced to human clinical
studies