Synthesis and effects on lipid regulation of 1-(4-hydroxyphenyl)ethanone derivatives
Wei Bao-kang · Zhongguo yaowu huaxue zazhi · 2013
1-(4-Hydroxyphenyl)ethanone(PHA)was found to have lipid-lowing activity in vivo,but it also has some adverse effects such as relatively toxicity because of the small molecular structure.Now the structure modification of it was made by esterification of hydroxyl with acyl chlorides and meanwhile modification of α-keto.The target compounds A1-A4 were prepared by substitution reaction from 2-bromo-1-(4-hydroxyphenyl)ethanone(2).2-Amino-1-(4-hydroxyphenyl)ethanone(3) synthesized from 2 via Delepine reaction was converted to the target compounds A5-A8 with the acyl chlorides which converted to compounds A9-A11 by sodium hydroxide.Starting from 1-Boc-piperazine via condensation,treated with trifluoroacetic acid and SN2 substitution of 2,the target compound A12 was obtained.All the novel compounds have been characterized by 1H-NMR and MS.Furthermore,the lipid regulation activities in the rats of these compounds were evaluated.The results showed that compound A5 exhibited good lipid-lowing activity.The pharmacology data suggest that both of TG and LDL-C in serum decreased by the compound A6 and the HDL-C increased by the compound A7.Preliminary analysis of the structure-activity relationship showed that enlarged the molecular structure of PHA was benefit for their activity and esterification of its hydroxyl could increase the activity of reducing triglyceride.This study provides several clues for designing new lipid regulation agents.