ISOF-CNR Dep. 'G. Ciamician', Bologna, Italy.
Bioorg Med Chem. 2013 Sep 15;21(18):5811-22. doi: 10.1016/j.bmc.2013.07.012. Epub 2013 Jul 16.
The enzyme α-glucosidase has attracted interest owing to its involvement in the digestive process of carbohydrate, its role in intracellular glycoprotein trafficking, tumorigenesis and viral infection. In this study, several members of a new family of N-heteroarylmethyl substituted azasugars were synthesized and evaluated as α-glucosidase inhibitors. We systematically investigated the effect of different N-substituents as well as the role of hydroxyl and carboxylate moieties on the piperidine ring. The compounds N-heteroarylmethyl-5-hydroxy-1,2,5,6-tetrahydropyridine-3-carboxylic acid emerged as potent α-glucosidase inhibitors. Unlike Acarbose and other clinically relevant α-glucosidase inhibitors, these compounds act through a reversible uncompetitive mechanism of inhibition which make them attractive candidates for drug development.
由于α-葡萄糖苷酶参与碳水化合物的消化过程、在细胞内糖蛋白运输、肿瘤发生和病毒感染中的作用，该酶引起了人们的兴趣。在这项研究中，合成了一系列新型 N-杂芳基取代氮杂糖的新成员，并将其作为α-葡萄糖苷酶抑制剂进行了评估。我们系统地研究了不同 N-取代基以及哌啶环上羟基和羧基的作用。N-杂芳基甲基-5-羟基-1,2,5,6-四氢吡啶-3-羧酸是有效的α-葡萄糖苷酶抑制剂。与阿卡波糖和其他临床相关的α-葡萄糖苷酶抑制剂不同，这些化合物通过可逆的非竞争性抑制机制发挥作用，这使它们成为药物开发的有吸引力的候选物。
