新型含取代哌嗪的5-(吡啶-3-基)-1,2,4-三唑Mannich碱和双Mannich碱的合成及生物活性

根据药物分子设计的活性基团组合原理,通过在1,2,4-三唑环的5位引入吡啶基,同时在4位芳基亚甲氨基的苯环上引入氟或三氟甲基,设计合成了一系列含氟、吡啶和哌嗪基团的1,2,4-三唑Mannich碱和双Mannich碱类化合物.通过核磁共振氢谱(~1H NMR)、碳谱(~(13)C NMR)和元素分析确证了目标化合物的结构.生物活性测试结果表明,部分化合物对油菜具有一定的除草活性;化合物2a,2d和2f(50 mg/L)对苹果轮纹病菌表现出较好的抑制活性,与对照药三唑酮活性相当;化合物2a,2b,2d和2i(180 mg/L)对酮醇酸还原异构酶(KARI酶)表现出了显著的离体抑制活性(抑制率51.7%~88.7%).

Synthesis and Biological Activities of Novel 5-(Pyridine-3-yl)-1,2,4-triazole Mannich Bases and Bis-Mannich Bases Containing Piperazine Moiety

According to the drug design principle of active groups combination, a series of 5-( pyridine-3-yl)-1 ,2 ,4-triazole Mannich bases and bis-Mannich bases containing piperazine and fluorine moieties was designed and synthesized through the Mannich reaction of 1,2,4-triazole thiol intermediate. All the structures of new title compounds were characterized by 1 H NMR, 13 C NMR and elemental analysis. The bioassay results showed that several compounds exhibited herbicidal activities against Brassica campestris in certain extent;compounds 2a, 2d and 2f possessed significant antifungal activities against P. piricola and were comparable with the control fungicide, triadimefon, at the concentration of 50 mg/L. Also, compounds 2a, 2b, 2d and 2i showed favorable in vitro ketol-acid reductoisomerase ( KARI ) inhibitory activities with inhibition rate of 51. 7%—88. 7% at 180 mg/L.