Discovery of 2-azetidinone and 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain as potential cholesterol absorption inhibitors

Bioorganic & Medicinal Chemistry Letters
Xinrui YuanQi Zhang

Abstract

Cholesterol absorption inhibitor (CAI) targeting Niemann-Pick C1-like1 protein was developed for the treatment of hyperlipidaemia and only ezetimibe was approved so far. For developing novel CAIs, we synthesized sixteen 2-azetidinone derivatives and thirteen 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain, and their inhibitory activity of cholesterol absorption was evaluated in Caco-2 cell line in vitro. Furthermore, top six compounds were measured by cytotoxicity and partition coefficient, and 2-azetidinone analogue 9e was selected for in vivo study. Finally, 9e considerably reduced total cholesterol, LDL-C, FFA and triglyceride in the serum and increased the rate of HDL-C to total cholesterol, suggesting it could regulate the lipid metabolism and act as a potent CAI.

References

Sep 21, 2005·Organic & Biomolecular Chemistry·Tobias RitterErick M Carreira
Apr 21, 2010·Lipids in Health and Disease·Dan FengRui-Dong Duan
Oct 4, 2011·Letters in Drug Design & Discovery·Yubin WangJinpei Zhou

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Citations

Jun 21, 2020·Mini Reviews in Medicinal Chemistry·Taíse H O LeiteMarcus Vinícius N de Souza

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