Introduction of fluorine to phenyl group of 4-(2-pyrimidinylamino)benzamides leading to a series of potent hedgehog signaling pathway inhibitors

  • Bioorg Med Chem Lett. 2017 Aug 1;27(15):3259-3263. doi: 10.1016/j.bmcl.2017.06.030.
Minhang Xin  1 ,  Liandi Zhang  2 ,  Jun Wen  2 ,  Han Shen  2 ,  Xinge Zhao  2 ,  Qiu Jin  2 ,  Feng Tang  2
Affiliations
  • 1. Department of Medicinal Chemistry, School of Pharmacy, Xi'an Jiaotong University, No 76, Yanta West Road, Xi'an 710061, PR China; Jiangsu Simcere Pharmaceutical Co. Ltd., No 699-18, Xuan Wu District, Nanjing 210042, PR China. Electronic address: [email protected].
  • 2. Jiangsu Simcere Pharmaceutical Co. Ltd., No 699-18, Xuan Wu District, Nanjing 210042, PR China.
PMID: 28642101 DOI: 10.1016/j.bmcl.2017.06.030
Abstract

In present study, a novel series of fluorine containing 4-(2-pyrimidinylamino)benzamide analogues were designed and synthesized. The Hedgehog (Hh) signaling inhibitory activities for these compounds were evaluated by a luciferase reporter method. The preliminary SAR was discussed and many compounds showed potent Hh signaling inhibitory activities. Compound 15h displayed the most potent inhibitory activity, with an IC50 of 0.050nM. This paper finds the introduction of fluorine to the 4-(2-pyrimidinylamino)benzamide scaffold can lead to a novel series of potent Hh signaling pathway inhibitors.

Keywords
4-(2-Pyrimidinylamino)benzamide scaffold; Fluorine; Hedgehog signaling pathway inhibitors; Most potent.
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