2. Academic Validation
  3. Synthesis and pharmacological evaluation of trifluoromethyl containing 4-(2-pyrimidinylamino)benzamides as Hedgehog signaling pathway inhibitors

Synthesis and pharmacological evaluation of trifluoromethyl containing 4-(2-pyrimidinylamino)benzamides as Hedgehog signaling pathway inhibitors

  • Bioorg Med Chem. 2016 Mar 1;24(5):1079-88. doi: 10.1016/j.bmc.2016.01.034.
Minhang Xin 1,  Liandi Zhang 2,  Jun Wen 2,  Han Shen 2,  Zhaoyu Liu 2,  Xinge Zhao 2,  Qiu Jin 2,  Mengyu Wang 2,  Lingfei Cheng 2,  Wei Huang 2,  Feng Tang 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: 26827136 DOI: 10.1016/j.bmc.2016.01.034
Abstract

In present study, a series of novel containing trifluoromethyl 4-(2-pyrimidinylamino)benzamide derivatives were designed by the fluorine scan strategy. Their Hh signaling inhibitory activities were evaluated by Gli-luciferase reporter method. The comprehensive SAR was discussed and several derivatives were found to display more potent Hh signaling inhibitory activity than positive drug vismodegib. Compound 13d was the most potent compound with IC50 of 1.44nM against Hh signaling pathway and also exhibited optimal PK properties in the in vivo PK properties study, deserved as an ideal lead compound for further study in future.

Keywords

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

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