154349-04-9Relevant academic research and scientific papers
Design, synthesis and biological evaluation of quinoline derivatives as HDAC class I inhibitors
Chen, Chen,Hou, Xuben,Wang, Guohua,Pan, Wenyan,Yang, Xinying,Zhang, Yingkai,Fang, Hao
, p. 11 - 23 (2017/04/06)
Inhibition of histone deacetylase (HDAC) has been regarded as a potential therapeutic approach for treatment of multiple diseases including cancer. Based on pharmacophore model of HDAC inhibitors, a series of quinoline-based N-hydroxycinnamamides and N-hydroxybenzamides were designed and synthesized as potent HDAC inhibitors. All target compounds were evaluated for their in?vitro HDAC inhibitory activities and anti-proliferative activities and the best compound 4a surpass Vorinostat in both enzymatic inhibitory activity and cellular anti-proliferative activity. In terms of HDAC isoforms selectivity, compounds 4a exhibited preferable inhibition for class I HDACs, especially for HDAC8, the IC50 value (442?nM) was much lower than that of Vorinostat (7468?nM). Subsequently, we performed class I & IIa HDACs whole cell enzyme assay to evaluate inhibitory activity in whole cell context. Compounds 4a and 4e displayed much better cellular activity for class I HDACs than that for class IIa HDACs, which indicated that 4a and 4e might be potent class I HDAC inhibitors. Meanwhile, flow cytometry analysis showed that compound 4a and 4e can promote cell apoptosis in?vitro.
Synthesis of 1-(4-substituted)benzyl-6-hydroxyisoquinolines with potential activity on Na+,K+-ATPase
Cerri,Mauri,Mauro,Melloni
, p. 1581 - 1592 (2007/10/02)
The synthesis of 1-(4-substituted)benzyl-6-hydroxyisoquinolines, to be evaluated in the displacement of the specific 3H-ouabain binding to Na+,K+-ATPase, is described. The key step involved a cyclization to the isoquinoline ring under Piclet-Gams conditions which was best performed with the 6-hydroxy group protected as the benzyl ether. When an unsaturated ester group was present in position 4 of the 1-benzyl group, this was best introduced before the cyclization step, since the Heck reaction on 1-(4- bromobenzyl)-6-hydroxyisoquinoline (8) with acrylic acid derivatives was not successful in all cases.
