Zhang Liandi, Xin Minhang, Shen Han, Wen Jun, Tang Feng, Tu Chongxing, Zhao Xinge, Wei Ping
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.
Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an 710061, PR China.
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3486-92. doi: 10.1016/j.bmcl.2014.05.066. Epub 2014 May 28.
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.
一系列新型的五元杂芳环稠合嘧啶衍生物，包括嘌呤、吡咯并[2,3 - d]嘧啶、吡咯并[3,2 - d]嘧啶、噻吩并[2,3 - d]嘧啶、噻吩并[3,2 - d]嘧啶和呋喃并[3,2 - d]嘧啶，已被确定为刺猬信号通路的有效抑制剂。描述了这些化合物的合成及构效关系。在这一系列新的刺猬信号通路抑制剂中，与维莫德吉相比，大多数化合物表现出显著的抑制活性，这表明五元杂芳环稠合嘧啶在目前报道的刺猬信号通路抑制剂结构骨架中是令人鼓舞的骨架，值得更多的探索和进一步研究。
