Department of Chemistry, Aarhus University, Langelandsgade 140, DK-8000 Aarhus C, Denmark.
Org Biomol Chem. 2018 Aug 29;16(34):6250-6261. doi: 10.1039/c8ob01433g.
Four new α-glucosidase inhibitors have been synthesised through 5-8 synthetic steps from a common synthetic intermediate obtained through a recently developed carbocyclisation. The compounds were designed as hybrids of the known glucosidase inhibitors valienamine, voglibose and miglitol. All four compounds showed activity against rat intestinal sucrase with the most potent inhibitor acting at low micromolar concentration. The newly synthesised compounds were not as potent as miglitol against sucrase but showed greater selectivity towards the tested glycosidases. The most potent inhibitors were docked into a homology model built for this study of rat intestinal sucrase explaining the difference in potency between two diastereoisomers with varying orientation of a secondary amine.
已经通过最近开发的碳环化反应从共同的合成中间体合成了四种新的α-葡萄糖苷酶抑制剂，通过 5-8 个合成步骤。这些化合物被设计为已知的葡萄糖苷酶抑制剂 valienamine、voglibose 和 miglitol 的杂合体。所有四种化合物对大鼠肠蔗糖酶均具有活性，最有效的抑制剂在低微摩尔浓度下起作用。新合成的化合物对蔗糖酶的活性不如 miglitol 强，但对测试的糖苷酶具有更高的选择性。最有效的抑制剂被对接入为这项大鼠肠蔗糖酶的同源模型研究构建的模型中，解释了两种非对映异构体之间的效力差异，它们的二级胺取向不同。
