Synthesis Of CETP Inhibitors Tetrahydroquinoline Compounds

Cardiovascular disease is a common cause of death, Atherosclerosis (AS) is the Pathological basis of cardiovascular disease and it is the occurrence of some diseases and the development of closely related. Extensive studies demonstrate that the increased HDL-C level is able to delay the development of AS, thereby reducing atherosclerotic cardiovascular risk, therefore, it is very interesting to develop some new therapeutic drugs against cardiovascular disease.Cholesterol ester transfer protein is a central role of the important elements in HDL metabolism. Inhibiting CETP could effectively raise HDL-C level and significant changing the pathogenesis of AS, so it is desirable for CETP inhibitor to function as therapeutic agents to treat and prevent the occurrences of cardiovascular disease.Based on the design of synthetic route to carry out systematic research, 1, 2, 3,4-tetrahydroquin oline compounds with ester-substituted on the aromatic ring may have good drug activity. On this basis and by the systematic research on the design of synthetic route, twenty 1, 2, 3, 4 -tetrahydroqui noline compounds which were not reported in the literature were designed and synthesize in the course of our research. Starting from 3-brmobenzaldehyde, the ester compounds were synthesized by nitration、Suzuki coupling、oxidation and estherification, The important intermediate-1,2, 3, 4-tetrahydroquinoline compounds were obtained by reducation、electrophilic addition and cyclization, then 3-substituted compounds were given by Mannich reaction. All the compounds were characteriz ed by ~1H-NMR and MS.The pharmacological activity of twenty new compounds is being screened.