The Synthesis And Activity Evaluation Of Novel Small-molecule CETP Inhibitors

Cholesteryl ester transfer protein(CETP) is a plasma glycoprotein which can mediate the transfer of neutral lipids in the blood among various lipoproteins.Neutral lipids can't circulate freely in plasma for their poor water solubility,such as triglycerides(TG),free cholesterol (FC) and cholesteryl esters(CE).As a result,they packed together and transported in larger lipoprotein particles that have amphipathic lipids and proteins as surface components. High-density lipoproteins(HDL) and low-density lipoproteins(LDL) help move cholesterol from and to the periphery respectively.This process is regulated by CETP which facilitates the transfer of CE from HDL to LDL with a balanced exchange of TG.Therefore,CETP inhibitor could be expected to raise plasma HDL cholesterol(HDLc) levels,lower LDL cholesterol(LDLc) levels,and provide a potential therapeutic benefit for patient with heart artery disease.A series of thio-based benzaza-heterocyclic CETP inhibitors were synthesized in this paper:3-[1-(2-ethylbutyl)cyclohexamido]-2-mercapto quinoline(compound 1-7),3-(1-(2-ethylbutyl)cyclohexamido)-4-mercapto quinoline(compound 2-7) and S-(2-(1-(2-ethylbutyl) cyclohexamido)-1-isoquinolyl) isobutanethioate(compound 3-9),and their activity as CETP inhibitors was evaluated.What's more,a novel environment friendly synthesis route by which the mercapto group could be protected was reported and optimized.By this route,the problem that there was great off odor in the experimentation was solved perfectly while the reaction time was shorted and the yields was elevated.