Abstract
Epidemiological studies have established an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol concentration, and incidence of coronary artery disease (CAD); thus, the development of novel therapies that attempt to exploit the atheroprotective functions of HDL is a major goal. Inhibition of cholesteryl ester transfer protein (CETP) is one of the approaches targeted to increase HDL cholesterol concentration. CETP is a glycoprotein involved in transporting lipoprotein particles and neutral lipids between HDL and low-density lipoproteins (LDL), and therefore CETP inhibitors could be useful agents in the future for treating dyslipidemia and related disorders. Guided by our previously reported pharmacophore and QSAR models for CETP inhibition, we synthesized and bioassayed a series of sulfonic acid ester and benzenesulfonamide derivatives that can serve as a promising lead compounds for the development of potential and selective CETP inhibitors. The most potent compound 6k illustrated an IC50 of 3.4 μM.
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Acknowledgments
The authors are grateful to the Scientific Research and Postgraduate Deanship at Al-Zaytoonah University of Jordan for sponsoring this project.
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Abu Khalaf, R., Abu Sheikha, G., Al-Sha’er, M. et al. Design, synthesis, and biological evaluation of sulfonic acid ester and benzenesulfonamide derivatives as potential CETP inhibitors. Med Chem Res 21, 3669–3680 (2012). https://doi.org/10.1007/s00044-011-9917-5
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DOI: https://doi.org/10.1007/s00044-011-9917-5
Keywords
- CETP inhibitors
- High-density lipoprotein
- Pharmacophore modeling
- Benzenesulfonamide
- Sulfonic acid ester