5-[(3,5-Dinitrobenzyl)sulfanyl]-1H-tetrazole | 1618101-63-5

• 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: 5-[(3,5-Dinitrobenzyl)sulfanyl]-1H-tetrazole
• 英文别名: 5-[(3,5-dinitrophenyl)methylsulfanyl]-1H-tetrazole；5-[(3,5-dinitrophenyl)methylsulfanyl]-2H-tetrazole
• CAS: 1618101-63-5
• 化学式: C₈H₆N₆O₄S
• 分子量: 282.239
• InChiKey: ULXHXXUJCVRQBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  171
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-[(3,5-Dinitrobenzyl)sulfanyl]-1H-tetrazole 、 乙酸酐 反应 10.0h， 以60%的产率得到2-(3,5-dinitrobenzylsulfanyl)-5-methyl-1,3,4-oxadiazole
  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
• 作为产物：
  描述：

  3,5-二硝基苄氯 在 sodium azide 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 3.0h， 生成 5-[(3,5-Dinitrobenzyl)sulfanyl]-1H-tetrazole
  参考文献：
  名称：

  四唑区域异构体在含硝基抗结核药开发中的作用†

  摘要：

  含有硝基取代基的四唑衍生物已被确认为有希望的抗结核药。在这项研究中，抗结核药的抗结核效力，选择性和毒性四唑检查了1，5-和2，5-区域异构体。我们制备了一系列的1-和2-烷基-5-苄基硫烷基-2 H-四唑及其衍生物硒具有各种硝基取代基的类似物。分离并使用1 H和/或13 C NMR明确鉴定这些1,5-和2,5-区域异构体。在制备的化合物中，1-和2-烷基-5-[（3,5-二硝基苄基）硫烷基] -2 H-四唑衍生物及其衍生物硒生物甾体显示出最高的抗分枝杆菌活性，对结核分枝杆菌CNCTC My 331/88的最小抑制浓度（MIC）值约为1μM（0.37–0.46μgmL -1）。与1-烷基异构体相比，2-烷基区域异构体始终表现出较高的抗分枝杆菌活性和对哺乳动物细胞系的体外毒性。与1-烷基异构体相反，2-烷基区域异构体的抗分枝杆菌活性受烷基取代基类型的影响较小。此外，3,5-二硝基苄基部分本身不

  DOI：

  10.1039/c4md00301b

文献信息

• 1-Substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their isosteric analogs: A new class of selective antitubercular agents active against drug-susceptible and multidrug-resistant mycobacteria
  作者：Galina Karabanovich、Jaroslav Roh、Tomáš Smutný、Jan Němeček、Petr Vicherek、Jiřina Stolaříková、Marcela Vejsová、Ida Dufková、Kateřina Vávrová、Petr Pávek、Věra Klimešová、Alexandr Hrabálek

  DOI：10.1016/j.ejmech.2014.05.069

  日期：2014.7

  In this work, a new class of highly potent antituberculosis agents, 1-substituted-5-[(3,5-dinitrobenzyl)sulfanyl]-1H-tetrazoles and their oxa and selanyl analogs, is described. The minimal inhibitory concentration (MIC) values reached 1 μM (0.36–0.44 μg/mL) against Mycobacterium tuberculosis CNCTC My 331/88 and 0.25–1 μM against six multidrug-resistant clinically isolated strains of M. tuberculosis

  在这项工作中，描述了一类新型的高效抗结核药，即1-取代的5-[（3,5-二硝基苄基）硫烷基] -1 H-四唑及其氧杂和硒基类似物。最小抑菌浓度（MIC）值达到了1μM（0.36-0.44微克/毫升）对结核分枝杆菌CNCTC我八十八分之三百三十一和0.25-1μM针对六个多药耐药性临床分离菌株的结核分枝杆菌。这些化合物的抗分枝杆菌作用具有高度特异性，因为它们对所研究的所有八种细菌菌株和八种真菌菌株均无效。此外，这些化合物在四种哺乳动物细胞系中均表现出较低的体外毒性（IC 50 > 30μM）。我们还检查了化合物的结构-活性关系，特别是硝基基团的数量和位置，四唑和苄基部分之间的连接基以及四唑本身对抗分枝杆菌活性的影响。在不对分枝杆菌活性产生负面影响的情况下，四唑上取代基R 1的相对较高的变异性可进一步优化毒性，并进一步优化1-取代的5-[（3,5-二硝基苄基）硫烷基]-的ADME性质。 1 H-四唑化合物。
• Tetrazole regioisomers in the development of nitro group-containing antitubercular agents
  作者：Galina Karabanovich、Jaroslav Roh、Ondřej Soukup、Ivona Pávková、Markéta Pasdiorová、Vojtěch Tambor、Jiřina Stolaříková、Marcela Vejsová、Kateřina Vávrová、Věra Klimešová、Alexandr Hrabálek

  DOI：10.1039/c4md00301b

  日期：——

  Tetrazole derivatives containing nitro substituents have been identified as promising antitubercular agents. In this study, the antitubercular potency, selectivity and toxicity of tetrazole 1,5- and 2,5-regioisomers were examined. We prepared a series of 1- and 2-alkyl-5-benzylsulfanyl-2H-tetrazoles and their selenium analogs with various nitro group substitutions. These 1,5- and 2,5-regioisomers were

  含有硝基取代基的四唑衍生物已被确认为有希望的抗结核药。在这项研究中，抗结核药的抗结核效力，选择性和毒性四唑检查了1，5-和2，5-区域异构体。我们制备了一系列的1-和2-烷基-5-苄基硫烷基-2 H-四唑及其衍生物硒具有各种硝基取代基的类似物。分离并使用1 H和/或13 C NMR明确鉴定这些1,5-和2,5-区域异构体。在制备的化合物中，1-和2-烷基-5-[（3,5-二硝基苄基）硫烷基] -2 H-四唑衍生物及其衍生物硒生物甾体显示出最高的抗分枝杆菌活性，对结核分枝杆菌CNCTC My 331/88的最小抑制浓度（MIC）值约为1μM（0.37–0.46μgmL -1）。与1-烷基异构体相比，2-烷基区域异构体始终表现出较高的抗分枝杆菌活性和对哺乳动物细胞系的体外毒性。与1-烷基异构体相反，2-烷基区域异构体的抗分枝杆菌活性受烷基取代基类型的影响较小。此外，3,5-二硝基苄基部分本身不
• 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.