Synthesis and biological evaluation of novel benzamide derivatives as potent smoothened antagonists

  • Bioorg Med Chem Lett. 2014 Mar 1;24(5):1426-31. doi: 10.1016/j.bmcl.2014.01.006.
Tian-Ming Wu  1 ,  Dao-Cai Wang  2 ,  Pu Xiang  1 ,  Jian-Nan Zhang  1 ,  Ya-Xiong Sang  1 ,  Hong-Jun Lin  1 ,  Jie Chen  1 ,  Gang Xie  1 ,  Hang Song  2 ,  Ying-Lan Zhao  3 ,  Yong-Mei Xie  4
Affiliations
  • 1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
  • 2. Department of Pharmaceutical and Biological Engineering, College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
  • 3. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
  • 4. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: [email protected].
PMID: 24491459 DOI: 10.1016/j.bmcl.2014.01.006
Abstract

A series of novel benzamide derivatives were prepared and evaluated using cell-based measurements. Among these compounds, 10f significantly inhibited Hedgehog signaling and showed equivalent or more potency than GDC-0449 in different tests. Furthermore, compound 10f potently inhibited the proliferation of Daoy, a Medulloblastoma cell line that is reported to be resistant to GDC-0449, which indicated a promising prospect in the treatment of Hedgehog signaling pathway related Cancer in clinical trial.

Keywords
Amide derivatives; Hedgehog; Smoothened antagonist.