2-((3-nitro-5-(trifluoromethyl)benzyl)sulfanyl)-5-(p-tolyl)-1,3,4-thiadiazole

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((3-nitro-5-(trifluoromethyl)benzyl)sulfanyl)-5-(p-tolyl)-1,3,4-thiadiazole
• 英文别名: 2-(4-Methylphenyl)-5-[[3-nitro-5-(trifluoromethyl)phenyl]methylsulfanyl]-1,3,4-thiadiazole；2-(4-methylphenyl)-5-[[3-nitro-5-(trifluoromethyl)phenyl]methylsulfanyl]-1,3,4-thiadiazole
• 化学式: C₁₇H₁₂F₃N₃O₂S₂
• 分子量: 411.428
• InChiKey: ZLMQHCMNWNAXFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  对甲基苯甲酸甲酯 在 硫酸 、 四丁基溴化铵 、 一水合肼 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 52.0h， 生成 2-((3-nitro-5-(trifluoromethyl)benzyl)sulfanyl)-5-(p-tolyl)-1,3,4-thiadiazole
  参考文献：
  名称：

  Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating Mycobacterium tuberculosis

  摘要：

  Herein, we report the discovery and structure activity relationships of 5-substituted-2-[(3,5-dinitrobenzyl)-sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles as a new class of antituberculosis agents. The majority of these compounds exhibited outstanding in vitro activity against Mycobacterium tuberculosis CNCTC My 331/88 and six multidrug-resistant clinically isolated strains of M. tuberculosis, with minimum inhibitory concentration values as low as 0.03 mu M (0.011-0.026 mu g/mL). The investigated compounds had a highly selective antimycobacterial effect because they showed no activity against the other bacteria or fungi tested in this study. Furthermore, the investigated compounds exhibited low in vitro toxicities in four proliferating mammalian cell lines and in isolated primary human hepatocytes. Several in vitro genotoxicity assays indicated that the selected compounds have no mutagenic activity. The oxadiazole and thiadiazole derivatives with the most favorable activity/toxicity profiles also showed potency comparable to that of rifampicin against the nonreplicating streptomycin-starved M. tuberculosis 18b-Lux strain, and therefore, these derivatives, are of particular interest.

  DOI：

  10.1021/acs.jmedchem.5b00608

文献信息

• Development of 3,5-Dinitrobenzylsulfanyl-1,3,4-oxadiazoles and Thiadiazoles as Selective Antitubercular Agents Active Against Replicating and Nonreplicating <i>Mycobacterium tuberculosis</i>
  作者：Galina Karabanovich、Júlia Zemanová、Tomáš Smutný、Rita Székely、Michal Šarkan、Ivana Centárová、Anthony Vocat、Ivona Pávková、Patrik Čonka、Jan Němeček、Jiřina Stolaříková、Marcela Vejsová、Kateřina Vávrová、Věra Klimešová、Alexandr Hrabálek、Petr Pávek、Stewart T. Cole、Katarína Mikušová、Jaroslav Roh

  DOI：10.1021/acs.jmedchem.5b00608

  日期：2016.3.24

  Herein, we report the discovery and structure activity relationships of 5-substituted-2-[(3,5-dinitrobenzyl)-sulfanyl]-1,3,4-oxadiazoles and 1,3,4-thiadiazoles as a new class of antituberculosis agents. The majority of these compounds exhibited outstanding in vitro activity against Mycobacterium tuberculosis CNCTC My 331/88 and six multidrug-resistant clinically isolated strains of M. tuberculosis, with minimum inhibitory concentration values as low as 0.03 mu M (0.011-0.026 mu g/mL). The investigated compounds had a highly selective antimycobacterial effect because they showed no activity against the other bacteria or fungi tested in this study. Furthermore, the investigated compounds exhibited low in vitro toxicities in four proliferating mammalian cell lines and in isolated primary human hepatocytes. Several in vitro genotoxicity assays indicated that the selected compounds have no mutagenic activity. The oxadiazole and thiadiazole derivatives with the most favorable activity/toxicity profiles also showed potency comparable to that of rifampicin against the nonreplicating streptomycin-starved M. tuberculosis 18b-Lux strain, and therefore, these derivatives, are of particular interest.