新型咪唑[2,1-b][1,3,4]噻二唑衍生物的合成及生物活性

Synthesis and Biological Activity of Novel Imidazo [2,1-b][1,3,4] thiadiazole Derivatives

合成了18个新型含苯并噁/噻唑啉酮结构的2,6-二取代咪唑[2,1-b][1,3,4]噻二唑衍生物5a^5i',即2-[(2-苯并噁/噻唑啉酮-3-基)甲基]-6-芳基-咪唑[2,1-b][1,3,4]噻二唑.利用红外光谱、核磁共振和元素分析对化合物的结构进行了表征.β2-肾上腺素受体(β2-AR)拮抗剂钙流筛选结果表明,部分目标化合物对β2-AR具有明显的拮抗作用,其中化合物5c'的拮抗效果最高,为70%.这些化合物可作为潜在的β2-AR拮抗剂.

To develop new β2-AR antagonists, eighteen novel 2,6-disubstituted imidazo[2,1-b] [1,3,4] thiadiazole derivatives containing 2-benzoxazolinone/benzothiazolinone moiety, 2-[ （ 2-benzoxazolinone/benzothiazolinone-3-yl）methyl]-6-aryl-imidazo[2,1-b] [1,3,4] thiadiazoles（5a-5i＇）, were synthesized by the condensation of compounds 4a and 4a＇ with α-bromoarylketones under reflux in dry ethanol. Their structures of the newly synthesized compounds were confirmed by IR, 1 H NMR and elemental analysis. The target compounds were screened as β2-adrenergic receptor antagonist. The result indicated that some of them display obvious antagonistic effects toβ2-AR, and compound 5c＇shows the highest antagonistic effect（70%）. They can be considered as potential candidates as novel β2-AR antagonists.