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为了寻找新型高效低毒的抗糖尿病分子,由Mannich反应一步合成了15个新的含有异噁唑结构单元的β-氨基酮,制备方法简便、反应条件温和、产品易纯化,收率为51.2%～89.3%.所得化合物结构均通过1HNMR,13CNMR,ESIMS和HRMS表征.生物活性实验结果表明,在低浓度范围,目标分子对蛋白质酪氨酸磷酸酶1B和α-葡萄糖苷酶抑制活性不高,但对过氧化物酶体增殖物激活受体的激动活性强度中等,其中化合物1-(3,4-二氯苯基)-3-(5-甲基异噁唑-3-氨基)-3-(6-甲氧基萘-2-基)-1-丙酮(15)的过氧化物酶体增殖因子活化受体(PPAR)激动活性最好,达到75.3%,值得进一步研究.还讨论了目标分子的合成条件及其结构-活性关系.
In order to find new high-effective and low-toxic anti-diabetic molecules, 15 new β-aminoketones containing isoxazole structural units were synthesized in one step by Mannich reaction. The preparation method is simple, the reaction conditions are mild and the products are easy to purify. The yield is 51.2% ~ 89.3% .The structures of the obtained compounds were characterized by 1HNMR, 13CNMR, ESIMS and HRMS, respectively.The results of biological activity showed that the inhibitory activity of target molecules on protein tyrosine phosphatase 1B and α-glucosidase was not high at low concentrations, But had a moderate intensity of agonistic activity on peroxisome proliferator-activated receptors in which the compound 1- (3,4-dichlorophenyl) -3- (5-methylisoxazol-3-amino) - (6-methoxynaphthalen-2-yl) -1-propanone (15) had the best peroxisome proliferator-activated receptor (PPAR) activity, reaching 75.3%, which deserved further study Synthesis of target molecules and their structure-activity relationship.