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 

机构地区：[1]Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College

出　　处：《Chinese Chemical Letters》2016年第1期11-15,共5页中国化学快报（英文版）

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

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.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.

关 键 词：Hsp90 inhibitor Anticancer drug RESORCINOL Tetrahydrotriazolopyrazine 

分 类 号：O626[理学—有机化学] TQ460.1[理学—化学]