Design And Synthesis Of Small-Molecule CETP Inhibitors

Low HDLc level in plasma was indicated as an important and independent risk factor for atherosclerosis (AS) besides high LDLc by recent researches. Cholesteryl ester transfer protein (CETP), a plasma glycoprotein, facilitates the transfer of cholesteryl esters (CE) from HDL to LDL and VLDL in exchange for tnglycerides. Inhibiting CETP activity may increase HDLc level in plasma, so CETP inhibitors would be promisingly used as novel antiatherosclerotic drugs.In this paper, 8 new thiol-compounds with different structures were designed based on a known thiol-based CETP inhibitor JTT-705. A new synthetic route and modified routes, in which benzyl group was used as protecting group, were applied to prepare above designed compounds, as well as JTT-705. The 8 thiol-compounds were in the following:(1) A symmetrical phenyl thioester was prepared from m-dichlorobenzene;(2) A naphthyl thioester was prepared from 2-Naphthylamine;(3) 5 pyridyl thiols were prepared from different pyridyl compounds;(4) A pyrazinyl thiol was prepared from Pyrazinamide.The primary tests for CETP inhibitive activity of above compounds are in process.