The class
Cyclic and bicyclic urea and sulfamide cores yield new CETP inhibitors effective in vivo (Bioorg Med Chem Lett 2020)
Original title: Cholesteryl ester transfer protein (CETP) inhibitors based on cyclic urea, bicyclic urea and bicyclic sulfamide cores
Researchers developed a series of CETP inhibitors built on cyclic urea, bicyclic urea, and bicyclic sulfamide core structures, designed to reduce transfer of cholesteryl esters from HDL to VLDL and LDL and thereby raise HDL cholesterol. Three exemplar compounds, 15, 31, and 45, demonstrated in vitro potency in inhibiting CETP transfer activity. Compounds 15 and 31 went on to show in vivo efficacy, increasing HDL cholesterol levels in cynomolgus-CETP transgenic mice. The paper describes the synthesis and biological evaluation of this compound series as candidate CETP inhibitors.
Original abstract
Cholesteryl ester transfer protein (CETP) inhibitors reduce the transfer of cholesteryl esters from the high-density lipoprotein (HDL-C) to apolipoprotein such as VLDL/LDL, with exchange of triglycerides. Thus, this inhibition increases the HDL-C levels, which is believed to lower the risk for heart disease and stroke. We report here a series of CETP inhibitors based on the cyclic, bicyclic urea and sulfamide cores. These CETP inhibitors exemplified by 15, 31, and 45 demonstrated in vitro potency in inhibiting the CETP transfer activity, and 15, 31 showing in vivo efficacy to increase HDL-C levels in cynomolgus-CETP transgenic mice. The synthesis and biological evaluations of these CETP inhibitors are described.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.