2. Academic Validation
  3. Five-membered heteroaromatic ring fused-pyrimidine derivatives: design, synthesis, and hedgehog signaling pathway inhibition study

Five-membered heteroaromatic ring fused-pyrimidine derivatives: design, synthesis, and hedgehog signaling pathway inhibition study

  • Bioorg Med Chem Lett. 2014 Aug 1;24(15):3486-92. doi: 10.1016/j.bmcl.2014.05.066.
Liandi Zhang 1,  Minhang Xin 2,  Han Shen 3,  Jun Wen 3,  Feng Tang 3,  Chongxing Tu 3,  Xinge Zhao 3,  Ping Wei 4
Affiliations

Affiliations

  • 1 The College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 30 Puzhu Road, Nanjing 211800, PR China; Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No. 699-18, Xuan Wu District, Nanjing 210042, PR China.
  • 2 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.
  • 3 Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No. 699-18, Xuan Wu District, Nanjing 210042, PR China.
  • 4 The College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, No. 30 Puzhu Road, Nanjing 211800, PR China. Electronic address: weiping@njtech.edu.cn.
PMID: 24923765 DOI: 10.1016/j.bmcl.2014.05.066
Abstract

A series of novel five-membered heteroaromatic ring fused-pyrimidine derivatives including purines, pyrrolo[2,3-d]pyrimidines, pyrrolo[3,2-d]pyrimidines, thieno[2,3-d]pyrimidines, thieno[3,2-d]pyrimidines and furo[3,2-d]pyrimidines have been identified to be potent inhibitors of Hedgehog signaling pathway. The synthesis and SAR of these compounds are described. Among this new series of Hedgehog signaling pathway inhibitors, most compounds exhibited significant inhibitory activity compared to vismodegib, indicating that the five-membered heteroaromatic ring fused-pyrimidines stand out as encouraging scaffolds among the currently reported structural skeletons for Hedgehog signaling pathway inhibitors, deserving more exploration and further investigation.

Keywords

Five-membered heteroaromatic ring fused-pyrimidine; Hedgehog signaling pathway; Inhibitors; Synthesis.

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