Bekircan Olcay, Ülker Serdar, Menteşe Emre
a Department of Chemistry, Faculty of Science , Karadeniz Technical University , Trabzon , Turkey .
b Department of Biology , and.
J Enzyme Inhib Med Chem. 2015 Dec;30(6):1002-9. doi: 10.3109/14756366.2014.1003213. Epub 2015 Feb 2.
In the present study, 2-[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetohydrazide (1) was used as starting compound for the synthesis of 2-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]acetyl}-4-thiosemicarbazides (2a-c) and 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-1,3,4-oxadiazole-2-thione (5). The cyclization of compounds 2a-c in the presence of NaOH resulted in the formation of 5-{[3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazol-4-yl]methyl}-4-alkyl/aryl-2,4-dihydro-3H-1,2,4-triazole-3-thiones (3a-c). Aminomethylation of compounds 3a-c and 5 with formaldehyde and N-methyl/phenylpiperazine furnished Mannich bases (4a-f and 6a-b). The newly synthesized compounds were well-characterized by IR, (1)H NMR, (13)C NMR, elemental analysis and mass spectral studies. They were also screened for their lipase and α-glucosidase inhibition. Among the tested compound 2c (IC50 = 2.50 ± 0.50 µM) showed the best anti-lipase activity and compounds 2c (IC50 = 3.41 ± 0.16 µM) and 6a (IC50 = 4.36 ± 0.10 µM) showed the best anti-α-glucosidase activity.
在本研究中，2-[3-(4-氯苯基)-5-(4-甲氧基苄基)-4H-1,2,4-三唑-4-基]乙酰肼(1)被用作起始化合物，用于合成2-{[3-(4-氯苯基)-5-(4-甲氧基苄基)-4H-1,2,4-三唑-4-基]乙酰基}-4-硫代氨基脲(2a - c)和5-{[3-(4-氯苯基)-5-(4-甲氧基苄基)-4H-1,2,4-三唑-4-基]甲基}-1,3,4-恶二唑-2-硫酮(5)。化合物2a - c在氢氧化钠存在下环化，生成5-{[3-(4-氯苯基)-5-(4-甲氧基苄基)-4H-1,2,4-三唑-4-基]甲基}-4-烷基/芳基-2,4-二氢-3H-1,2,4-三唑-3-硫酮(3a - c)。化合物3a - c和5与甲醛和N-甲基/苯基哌嗪进行氨甲基化反应，得到曼尼希碱(4a - f和6a - b)。新合成的化合物通过红外光谱、(1)H核磁共振、(13)C核磁共振、元素分析和质谱研究进行了充分表征。它们还被筛选了脂肪酶和α-葡萄糖苷酶抑制活性。在测试的化合物中，化合物2c(IC50 = 2.50 ± 0.50 μM)表现出最佳的抗脂肪酶活性，化合物2c(IC50 = 3.41 ± 0.16 μM)和6a(IC50 = 4.36 ± 0.10 μM)表现出最佳的抗α-葡萄糖苷酶活性。
