2. Academic Validation
  3. Cholesteryl ester transfer protein (CETP) inhibitors based on cyclic urea, bicyclic urea and bicyclic sulfamide cores

Cholesteryl ester transfer protein (CETP) inhibitors based on cyclic urea, bicyclic urea and bicyclic sulfamide cores

  • Bioorg Med Chem Lett. 2021 Jan 15;32:127668. doi: 10.1016/j.bmcl.2020.127668.
Jian Liu 1,  Patrick P Shao 2,  Deodial Guiadeen 2,  Arto Krikorian 2,  Wanying Sun 2,  Qiaolin Deng 2,  Anne-Marie Cumiskey 3,  Ruth A Duffy 3,  Beth A Murphy 3,  Kaushik Mitra 4,  Douglas G Johns 3,  Joseph L Duffy 2,  Petr Vachal 2
Affiliations

Affiliations

  • 1 Discovery Chemistry, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA. Electronic address: [email protected].
  • 2 Discovery Chemistry, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • 3 Discovery Biology, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • 4 Department of Drug Metabolism and Pharmacokinetics, Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
PMID: 33161125 DOI: 10.1016/j.bmcl.2020.127668
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.

Keywords

Bicyclic sulfamide; CETP inhibitors; Cyclic and bicyclic urea; HDL-C.

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