一系列2-磺酰胺基/三氟甲基-6-取代咪唑并[2,1-b]-1,3,4-噻二唑衍生物的合成及其抗结核活性
Synthesis and anti-tubercular activity of a series of 2-sulfonamido/trifluoromethyl-6-substituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives.
作者信息
Gadad Andanappa K, Noolvi Malleshappa N, Karpoormath Rajshekhar V
机构信息
Department of Medicinal Chemistry, College of Pharmacy, JN Medical College, Nehru Nagar, Belgaum 590 010, Karnataka, India.
出版信息
Bioorg Med Chem. 2004 Nov 1;12(21):5651-9. doi: 10.1016/j.bmc.2004.07.060.
A series of 2-sulfonamido/trifluoromethyl-6-(4'-substituted aryl/heteroaryl)imidazo[2,1-b]-1,3,4-thiadiazole derivatives (II) have been synthesized by reaction of 2-amino-5-sulfonamido/trifluoromethyl-1,3,4-thiadiazoles and an appropriate alpha-haloaryl/heteroaryl ketones. Further 5-bromo (III), 5-thiocyanato (IV), 5-gaunylhydrazone (V) derivatives were synthesized in order to study the effect of these substituents on biological activity. Structures of these compounds were established by IR, (1)H NMR, (13)C NMR, Mass and HRMS. The selected compounds were evaluated for their preliminary in vitro anti-tuberculosis activity against Mycobacterium tuberculosis H37Rv strain using radiometric BACTEC and broth dilution assay methods. The results show that compounds 5, 7, 8, 10 and 12 exhibited moderate to good anti-tubercular activity with percentage inhibition of 29, 43, 58, 31 and 41, respectively, at a MIC of >6.25 microg/mL. Compound 18 showed a MIC of 20 microg/mL.
通过2-氨基-5-磺酰胺基/三氟甲基-1,3,4-噻二唑与适当的α-卤代芳基/杂芳基酮反应，合成了一系列2-磺酰胺基/三氟甲基-6-(4'-取代芳基/杂芳基)咪唑并[2,1-b]-1,3,4-噻二唑衍生物（II）。为了研究这些取代基对生物活性的影响，进一步合成了5-溴（III）、5-硫氰酸根合（IV）、5-胍基腙（V）衍生物。通过红外光谱、核磁共振氢谱、核磁共振碳谱、质谱和高分辨质谱确定了这些化合物的结构。使用放射性BACTEC和肉汤稀释测定法，对所选化合物针对结核分枝杆菌H37Rv菌株的初步体外抗结核活性进行了评估。结果表明，化合物5、7、8、10和12表现出中度至良好的抗结核活性，在最低抑菌浓度>6.25μg/mL时，抑制率分别为29%、43%、58%、31%和41%。化合物18的最低抑菌浓度为20μg/mL。
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