Design and synthesis of novel 2-methyl-4,5-substitutedbenzo[f]-3,3a,4,5-tetra-hydro-pyrazolo[1,5-d][1, 4]oxazepin-8(7H)-one derivatives as telomerase inhibitors

作者：Liu, Xin-Hua^*; Jia, Ying-Ming; Song, Bao-An; Pang, Zhi-xiang; Yang, Song

来源：Bioorganic & Medicinal Chemistry Letters, 2013, 23(3): 720-723.

DOI：10.1016/j.bmcl.2012.11.101

• Synthesis
• Hydropyrazolo-oxazepine
• PI3K/AKT pathway
• Antitumor agents

Eight novel 4,5-tetrahydropyrazolo[1,5-d][1,4] oxazepine derivatives have been synthesized and purified to be screened for anticancer activity. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 4a showed the most potent inhibitory activity with IC50 value at 0.78 +/- 0.22 mu M. Western blot assays showed that compounds 4a and 4b could inhibit expression of Cyclin D1, TERT, phospho-AKT and PI3K/AKT pathway.

• 单位
  安徽工业大学; 安徽医科大学; 贵州大学