标题：Design, synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors.
作者：Zhang Y;Feng J;Liu C;Zhang L;Jiao J;Fang H;Su L;Zhang X;Zhang J;Li M;Wang B;Xu W
作者机构：[Zhang, Y] Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, China;[ Feng, J] Department of Medicin 更多
通讯作者地址：[Xu, WF]Shandong Univ, Sch Pharm, Dept Med Chem, Jinan 250012, Shandong, Peoples R China.
来源：Bioorganic and medicinal chemistry
关键词：1,2,3,4-Tetrahydroisoquinoline-3-carboxylic acid derivatives; Histone; deacetylases; Inhibitor; Synthesis
摘要：Histone deacetylases (HDACs) are enzymes involved in tumor genesis and development. Herein, we report a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDACs inhibitors. The preliminary biological screening showed that most of our compounds exhibited potent inhibitory activity against HDACs. Within this series, five compounds, 13a (IC(50)=0.58+/-0.10 microM), 7d (IC(50)=1.00+/-0.16 microM), 8l (IC(50)=1.06+/-0.14 microM), 7i (IC(50)=1.17+/-0.19 microM) and 7a (IC(50)=1.29+/-0.15 microM) possessed better HDACs inhibitory activity than Vorinostat (IC(50)=1.48+/-0.20 microM). So these five compounds could be used as novel lead compounds for further design of HDACs inhibitors. The anti-proliferative activities of a few compounds and the structure-activity relationships are also briefly discussed.