4,5,6,7-Tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine as a new scaffold for heat shock protein 90 inhibitors

作     者：Meng-Yi Xu Ni-Na Xue Di Liu Yu-Mei Zhou Wei Li Yong-Qiang Li Xiao-Guang Chen Xiao-Ming Yu 

作者机构：Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2016年第27卷第1期

页      面：11-15页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 10[医学] 

基　　金：financially supported by the National Natural Science Foundation of China (No. 21272279) 

主　　题：Hsp90 inhibitor Anticancer drug Resorcinol Tetrahydrotriazolopyrazine 

摘      要：Heat shock protein 90（hsp90） is a promising anticancer drug target. A library of 2,4-dihydroxyphenyl（resorcinol） substituted 4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine compounds that target this protein were designed and prepared based on our earlier study. The compounds were tested in five cancer cell lines and seven of them showed notable anticancer activity（IC_（50）2-10 mmol/L）. The active subset compounds were further subjected to a polarized fluorescent assay and exhibited high binding affinity toward purified hsp90（IC_（50）60-100 nmol/L）. These results indicated that the tetrahydrotriazolopyrazine motif of the molecules may represent a novel scaffold for the development of hsp90 inhibitors.