Cholesteryl ester transfer protein (CETP) inhibitors based on cyclic urea, bicyclic urea and bicyclic sulfamide cores
| Autor: | Kaushik Mitra, Anne-Marie Cumiskey, Beth Ann Murphy, Qiaolin Deng, Deodial Guiadeen, Douglas G. Johns, Wanying Sun, Joseph L. Duffy, Arto D. Krikorian, Ruth A. Duffy, Patrick P. Shao, Petr Vachal, Jian Liu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Very low-density lipoprotein
Apolipoprotein B Clinical Biochemistry Pharmaceutical Science Mice Transgenic 01 natural sciences Biochemistry chemistry.chemical_compound Bridged Bicyclo Compounds Mice Structure-Activity Relationship In vivo Drug Discovery Cholesterylester transfer protein Animals Humans Urea Molecular Biology Sulfamide Dyslipidemias Sulfonamides Bicyclic molecule biology 010405 organic chemistry Anticholesteremic Agents Organic Chemistry Cholesterol HDL 0104 chemical sciences Cholesterol Ester Transfer Proteins carbohydrates (lipids) 010404 medicinal & biomolecular chemistry chemistry Cyclization biology.protein Molecular Medicine lipids (amino acids peptides and proteins) Lipoprotein |
| Zdroj: | Bioorganicmedicinal chemistry letters. 32 |
| ISSN: | 1464-3405 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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