N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, 9, Akademika Lavrentieva Ave., Novosibirsk 630090, Russia.
Molecules. 2022 Dec 7;27(24):8663. doi: 10.3390/molecules27248663.
Natural and synthetic coumarins are often considered privileged scaffolds for obtaining pharmacological agents with hypoglycemic activity. Chemical modification of coumarins often leads to antidiabetic agents with greater efficacy. In the present work, twenty monoterpene-substituted 7-hydroxycoumarins were synthesized. A new approach using the Mitsunobu reaction was shown to be effective for the synthesis of target compounds. All of the synthesized compounds were evaluated in an oral glucose tolerance test, and two of them containing geranyl and (-)-myrtenyl substituents showed in vivo hypoglycemic action. A possible mechanism of action of these compounds may include inhibition of DPP IV, which was proved in an in vitro test.
天然和合成香豆素通常被认为是获得具有降血糖活性的药理制剂的优势骨架。香豆素的化学修饰常常导致具有更高疗效的抗糖尿病药物。在本工作中,合成了二十种单萜取代的 7-羟基香豆素。证明使用 Mitsunobu 反应的新方法对于目标化合物的合成是有效的。所有合成的化合物都在口服葡萄糖耐量试验中进行了评估,其中含有香叶基和(-)-桃金娘烯基取代基的两种化合物表现出体内降血糖作用。这些化合物的可能作用机制可能包括抑制 DPP IV,这在体外试验中得到了证明。