Demirbas Ahmet, Sahin Deniz, Demirbas Neslihan, Karaoglu Sengül Alpay
Department of Chemistry, Karadeniz Technical University, Trabzon, Turkey.
Eur J Med Chem. 2009 Jul;44(7):2896-903. doi: 10.1016/j.ejmech.2008.12.005. Epub 2008 Dec 16.
4-Amino-2-[(5-arylamino-4,5-dihydro-1,3,4-thiadiazol-2-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (3a-c) were obtained in acidic media via the formation of 2-[(4-amino-3-aryl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetyl]-N-arylhydrazinecarbothioamides (2a-c), and then, compound 3b was converted to methylated derivative, 4. The basic treatment of carbothioamide derivatives, 2a-c, afforded 4-amino-2-[(4-aryl-5-sulphanyl-4H-1,2,4-triazol-3-yl)methyl]-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (5a-c). The alkylation reactions of compounds 4H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one derivatives (5a-c) were performed by using methyl iodide or ethyl bromide in the presence of sodium ethoxide, while the treatment of the same intermediates, 5a-c, with aromatic aldehydes produced 2-{[4-(4-aryl)-5-sulphanyl-4H-1,2,4-triazol-3-yl]methyl}-4-(arylmethylene)amino-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-ones (8a-d). The synthesis of 4-amino-(or arylideneamino)-5-(4-methylphenyl)-2-{[(4-methylpiperazin-1-yl or morpholin-4-ylethyl)methyl]-4-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones (7a, b and 9) was performed by a one pot three-component Mannich reaction involving the corresponding compounds, 4-(substituted)amino-4H-1,2,4-triazol-3-ylmethyl-5-(4-methylphenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one derivatives 5a, b and 8a, methylpiperazine or 2-(4-morpholino)ethylamine and formaldehyde. The newly synthesized compounds were well characterized by elemental analyses, IR, (1)H NMR, (13)C NMR and mass spectral studies. They were also screened for their microbial activities. The antimicrobial activity study revealed that some of which 2a, c, 3c, 5a-c, 8a-d showed good activity against a variety of microorganisms.
4-氨基-2-[(5-芳基氨基-4,5-二氢-1,3,4-噻二唑-2-基)甲基]-5-(4-甲基苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮(3a - c)是在酸性介质中通过形成2-[(4-氨基-3-芳基-5-氧代-4,5-二氢-1H-1,2,4-三唑-1-基)乙酰基]-N-芳基肼基硫代酰胺(2a - c)得到的，然后，化合物3b转化为甲基化衍生物4。对硫代酰胺衍生物2a - c进行碱处理，得到4-氨基-2-[(4-芳基-5-硫烷基-4H-1,2,4-三唑-3-基)甲基]-5-(4-甲基苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮(5a - c)。化合物4H-1,2,4-三唑-3-基甲基-5-(4-甲基苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮衍生物(5a - c)的烷基化反应是在乙醇钠存在下用碘甲烷或溴乙烷进行的，而用芳香醛处理相同的中间体5a - c则生成2-{[4-(4-芳基)-5-硫烷基-4H-1,2,4-三唑-3-基]甲基}-4-(亚芳基)氨基-5-(4-甲基苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮(8a - d)。4-氨基-(或亚芳基氨基)-5-(4-甲基苯基)-2-{[(4-甲基哌嗪-1-基或吗啉-4-基乙基)甲基]-4-芳基-5-硫代-4,5-二氢-1H-1,2,4-三唑-3-基}甲基-2,4-二氢-3H-1,2,4-三唑-3-酮(7a、b和9)的合成是通过一锅三组分曼尼希反应进行的，该反应涉及相应的化合物4-(取代)氨基-4H-1,2,4-三唑-3-基甲基-5-(4-甲基苯基)-2,4-二氢-3H-1,2,4-三唑-3-酮衍生物5a、b和8a、甲基哌嗪或2-(4-吗啉基)乙胺和甲醛。新合成的化合物通过元素分析、红外光谱、(1)H核磁共振、(13)C核磁共振和质谱研究进行了充分表征。它们还进行了微生物活性筛选。抗菌活性研究表明，其中一些化合物2a、c、3c、5a - c、8a - d对多种微生物表现出良好的活性。
