Multifunctional aldose reductase inhibitors based on 2H-benzothiazine 1,1-dioxide

作者：Han, Zhongfei; Hao, Xin; Gao, Zehong; Ma, Bing; Zhu, Changjin^*

来源：RSC Advances, 2016, 6(16): 12761-12769.

DOI：10.1039/c5ra25984c

• ACETIC-ACID DERIVATIVES
• ANTIOXIDANT ACTIVITY
• 5-ARYLIDENE-4-THIAZOLIDINONE DERIVATIVES
• DIABETIC COMPLICATIONS
• IN-VITRO
• POTENT
• NEUROPATHY
• DESIGN
• SCAFFOLD
• DOCKING

A series of benzothiazine derivatives were designed and synthesized for the development of drug candidates for diabetic complications. A number of derivatives having a phenolic hydroxyl-substituted N2-aromatic side chain and a C4-acetic acid head group on the core structure were found to be potent and selective aldose reductase inhibitors. 8a with a phenolic 4-hydroxyl at N2-styryl side chain was proved to be the most active with an IC50 value of 0.094 mu M. All compounds with the N2-styryl side chain showed good antioxidant activity using the DPPH radical scavenging test, and among them, compounds with phenolic hydroxyl-substituted N2-styryl were potent both in activities of ALR2 inhibition and antioxidation. The results suggest a success in the development of multifunctional aldose reductase inhibitors based on the benzothiazine framework.

• 出版日期2016
• 单位北京理工大学