Discovery of PF-04449913, a Potent and Orally Bioavailable Inhibitor of Smoothened
详细信息 查看全文
- 作者：Michael J. Munchhof ; Qifang Li ; Andrei Shavnya ; Gary V. Borzillo ; Tracey L. Boyden ; Christopher S. Jones ; Susan D. LaGreca ; Luis Martinez-Alsina ; Nandini Patel ; Kathleen Pelletier ; Larry A. Reiter ; Michael D. Robbins ; George T. Tkalcevic
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：February 9, 2012
- 年：2012
- 卷：3
- 期：2
- 页码：106-111
- 全文大小：301K
- 年卷期：v.3,no.2(February 9, 2012)
- ISSN：1948-5875
文摘
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.