Synthesis and evaluation of 4-(2-pyrimidinylamino) benzamides inhibitors of hedgehog signaling pathway

  • Bioorg Med Chem Lett. 2014 Feb 1;24(3):983-8. doi: 10.1016/j.bmcl.2013.12.050.
Minhang Xin  1 ,  Jun Wen  2 ,  Feng Tang  2 ,  Chongxing Tu  2 ,  Wei Huang  2 ,  Han Shen  2 ,  Xinge Zhao  2 ,  Lingfei Cheng  2 ,  Mengyu Wang  2 ,  Liandi Zhang  2
Affiliations
  • 1. Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an 710061, P.R. China; Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China. Electronic address: [email protected].
  • 2. Jiangsu Simcere Pharmaceutical Co. Ltd., Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, P.R. China.
PMID: 24405704 DOI: 10.1016/j.bmcl.2013.12.050
Abstract

A novel series of Hedgehog signaling pathway inhibitors has been designed based on the 4-(2-pyrimidinylamino) benzamides scaffold. The synthesis and SAR of these compounds are described. Optimization leads to the identification of compound 3c, a potent and orally available agent with improved physicochemical and pharmacokinetic properties.

Keywords
Hedgehog signaling pathway; Inhibitors; Pharmacokinetic properties; SAR.