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

作者：Yuan, Xinrui; Lu, Peng; Xue, Xiaojian; Qin, Hui; Fan, Chen; Wang, Yubin^*; Zhang, Qi

来源：Bioorganic & Medicinal Chemistry Letters, 2016, 26(3): 849-853.

DOI：10.1016/j.bmcl.2015.12.077

• 2-Azetidinone
• 1H-Pyrrole-2,5-dione
• Sulfonamide group
• Cholesterol absorption inhibitor
• Caco-2 cell line

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.

• 出版日期2016-2-1
• 单位南京工业大学