Citation: Meng-Yi Xu, Ni-Na Xue, Di Liu, Yu-Mei Zhou, Wei Li, Yong-Qiang Li, Xiao-Guang Chen, Xiao-Ming Yu. 4,5,6,7-Tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine as a new scaffold for heat shock protein 90 inhibitors[J]. Chinese Chemical Letters, ;2016, 27(01): 11-15. doi: 10.1016/j.cclet.2015.09.024 shu

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

1.
Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China

Corresponding author: Xiao-Guang Chen, Xiao-Ming Yu,
Received Date: 2 July 2015
Available Online: 18 August 2015
Fund Project: This project is financially supported by the National Natural Science Foundation of China(No. 21272279). (No. 21272279)

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(IC₅₀ 2-10μmol/L). The active subset compounds were further subjected to a polarized fluorescent assay and exhibited high binding affinity toward purified hsp90(IC₅₀ 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.
- Hsp90 inhibitor,
- Anticancer drug,
- Resorcinol,
- Tetrahydrotriazolopyrazine
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沈阳化工大学材料科学与工程学院沈阳 110142