2. Academic Validation
  3. Discovery of novel 4-(2-pyrimidinylamino)benzamide derivatives as highly potent and orally available hedgehog signaling pathway inhibitors

Discovery of novel 4-(2-pyrimidinylamino)benzamide derivatives as highly potent and orally available hedgehog signaling pathway inhibitors

  • Eur J Med Chem. 2016 Mar 3:110:115-25. doi: 10.1016/j.ejmech.2016.01.018.
Minhang Xin 1,  Liandi Zhang 2,  Qiu Jin 2,  Feng Tang 2,  Jun Wen 2,  Liyun Gu 2,  Lingfei Cheng 2,  Yong Zhao 2
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Xi'an 710061, PR China. Electronic address: xmhcpu@163.com.
  • 2 Jiangsu Simcere Pharmaceutical Co. Ltd., No 699-18, Xuan Wu District, Nanjing 210042, PR China.
PMID: 26820554 DOI: 10.1016/j.ejmech.2016.01.018
Abstract

A series of novel Hedgehog signaling pathway inhibitors have been designed by structural modification based on the former reported scaffold of 4-(2-pyrimidinylamino)benzamide. The SAR for this series was described and many derivatives showed potent inhibitory activity. Among these compounds, compounds 12af and 12bf were identified to have high potency and optimal PK profiles. Although both of compounds 12af and 12bf did not show strong antitumor efficacy in LS-174T nude mice model, they were promising candidates as Hh signaling inhibitors due to great potency against Hh signaling pathway and outstanding PK properties, deserving further evaluation in Other Hh signaling operative tumor models.

Keywords

4-(2-pyrimidinylamino)benzamide; Hedgehog signaling pathway inhibitors; In vivo; SAR.

Figures