色酮连噁二唑(啉)衍生物的合成及抗炎活性研究

Synthesis and anti-inflammatory activity of chromone-oxadiazole(line)derivatives

以2,4,6-三羟基苯乙酮、草酸二乙酯等为原料,经过羟基保护、合环、肼解、酰腙化后,在两种不同的条件下关环,合成得到10个新型的色酮连噁二唑(啉)衍生物,利用1H NMR、^(13)C NMR和HRMS对其结构进行了确证。通过体外环氧合酶2(COX-2)的抑制活性评价发现,目标化合物6a、6b、6c、7h和7i具有良好的COX-2抑制作用。经分子柔性对接发现,其结果与生物活性试验具有一致性。本文为进一步研发新型色酮类抗炎药物提供了重要的参考依据。

Ten novel chromone-oxadiazole(line)derivatives were synthesized by using 2,4,6-trihydroxyacetophenone and diethyl ox-alate as raw materials via multi-step reactions,such as hydroxyl protection,cyclization,hydrazolysis and hydrazylation,finally closed ring under two different conditions.The structure of the target compounds were confirmed by ^(1)H NMR,^(13)C NMR and HRMS.In vitro experiments,compounds 6a,6b,6c,7h and 7i showed good inhibition of COX-2.The results of molecular flexible docking were found to be consistent with the bioactivity assay.This paper provided an important reference for the further development of novel chromones as anti-inflammatory drugs.