Design and synthesis of N-(3,5-difluoro-4-hydroxyphenyl)benzenesulfonamides as aldose reductase inhibitors

详细信息	查看全文 | 推荐本文 |

• 作者：Polyxeni Alexiou ; Ioannis Nicolaou ; Milan Stefek ; Albin Kristl ; Vassilis J. Demopoulos
• 关键词：Antidiabetic aldose reductase inhibitors ; Non-classical bioisosterism ; Antioxidant activity ; Permeability
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 April 2008
• 卷：16
• 期：7
• 页码：3926-3932
• 文件大小：192 K

摘要

N-(3,5-Difluoro-4-hydroxyphenyl)benzenesulfonamide (ng>4ng>) and its derivatives ng>5ng>–ng>7ng> were prepared as putative bioisosteres of the previously reported aldose reductase inhibitors, which are the N-benzenesulfonylglycine derivatives ng>Ing>–ng>IVng>. The in vitro aldose reductase inhibitory activity of the prepared compounds is higher than that of the respective glycine derivatives. Furthermore, the parent compound ng>4ng> reveals high antioxidant potential. Additionally, the intestine permeability of ng>4ng> is determined, and there is initial evidence that there is an operating influx mechanism. Overall, the data indicate that the presented chemotype could serve as a core structure for the design of putative pharmacotherapeutic agents, aiming to the long-term complications of diabetes mellitus.