新型1,2,4-三唑三氮烯衍生物的合成及其生物活性

Synthesis and Biological Activities of Novel 1,2,4-Triazole Triazene Derivatives

以对氨基苯甲酸为原料,经多步反应合成了16个未见文献报道的1,2,4-三唑三氮烯衍生物.利用~1H NMR~,(13)C NMR和HRMS对标题化合的结构进行了表征.衍生物的细胞毒活性测试结果表明,2-[4-(3,3-二甲基三氮烯-1-基)苯基]-3-氨基-4-S-(4-氯基苄基)-1,2,4-三唑(6g)、2-[4-(3,3-二甲基三氮烯-1-基)苯基]-3-氨基-4-S-(2,4-二氯基苄基)-1,2,4-三唑(6h)、2-[4-(3,3-甲基苯甲基三氮烯-1-基)苯基]-3-氨基-4-S-苄基-1,2,4-三唑(6i)、2-[4-(3,3-甲基苯甲基三氮烯-1-基)苯基]-3-氨基-4-S-(4-甲基苄基)-1,2,4-三唑(6j)、2-[4-(3,3-甲基苯甲基三氮烯-1-基)苯基]-3-氨基-4-S-(4-甲氧基苄基)-1,2,4-三唑(6l)、2-[4-(3,3-甲基苯甲基三氮烯-1-基)苯基]-3-氨基-4-S-(2,4-二氯基苄基)-1,2,4-三唑(6p)对膀胱癌细胞具有较好的抑制作用,其IC50值分别为23.883,5.512,8.731,8.077,5.590和12.195μmol/L,化合物6h,6i,6j,6l对前列腺癌细胞具有较好的抑制作用,其IC50值分别为13.690,21.908,10.772和4.827μmol/L.

Sixteen novel 1,2,4-triazole triazene derivatives were synthesized in multiple steps from the p-aminobenzoic acid. Their structures were confirmed by ~1 H NMR, ^（13）C NMR and HRMS. All the target compounds were evaluated for their anticancer activity. Among them, 2-[4-（3,3-dimethyltriazol-1-yl）phenyl]-3-amino-4-S-（4-chlorobenzyl）-1,2,4-triazole（6g）, 2-[4-（3,3-dimethyltriazol-1-yl）phenyl]-3-amino-4-S-（2,4-dichlorobenzyl）-1,2,4-triazole（6 h）, 2-[4-（3,3-methylbenzyltriazen-1-yl）-phenyl]-3-amino-4-S-benzyl-1,2,4-trioxazole（6i）, 2-[4-（3,3-methylbenzyltriazen-1-yl）phenyl]-3-amino-4-S-（4-methylbenzyl）-1,2,4-triazole（6 j）, 2-[4-（3,3-methylbenzyltriazen-1-yl）phenyl]-3-amino-4-S-（4-methoxybenzyl）-1,2,4-triazole（6l）, 2-[4-（3,3-methylbenzyltriazen-1-yl）phenyl]-3-amino-4-S-（2,4-di-chlorobenzyl）-1,2,4-triazole（6p） exhibited good anti-cancer activity against J82 cells with the IC_（50） values of 23.883, 5.512, 8.731, 8.077, 5.590 and 12.195 μmol/L, respectively. And compounds6h, 6i, 6j, 6l exhibited good anti-cancer activity against DU145 cells with the IC_（50） values of 13.690, 21.908, 10.772 and 4.827 μmol/L, respectively.