2-((3,5-dinitrobenzyl)sulfanyl)-5-methyl-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-((3,5-dinitrobenzyl)sulfanyl)-5-methyl-1,3,4-thiadiazole
• 英文别名: 2-(3,5-dinitrobenzylsulfanyl)-5-methyl-1,3,4-thiadiazole；2-[(3,5-Dinitrophenyl)methylsulfanyl]-5-methyl-1,3,4-thiadiazole；2-[(3,5-dinitrophenyl)methylsulfanyl]-5-methyl-1,3,4-thiadiazole
• 化学式: C₁₀H₈N₄O₄S₂
• 分子量: 312.33
• InChiKey: DTURUMXNURKHJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  171
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,5-二硝基苄氯 、 2-巯基-5-甲基-1,3,4-噻二唑 在 四丁基溴化铵 、 sodium hydroxide 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 12.0h， 生成 2-((3,5-dinitrobenzyl)sulfanyl)-5-methyl-1,3,4-thiadiazole
  参考文献：
  名称：

  [EN] OXA- AND THIA-DIAZOLES USEFUL IN THE TREATMENT OF TUBERCULOSIS
  [FR] OXADIAZOLES ET THIADIAZOLES UTILES DANS LE TRAITEMENT DE LA TUBERCULOSE

  摘要：

  一种通式(1)的取代二唑，其中X是0或S；R选自包括以下组：H，NH2-，C1-C11n烷基，环己基-，苄基-，苯基-，吡啶基-或苯基-，在2、3、4或5的位置上，被一个或多个电子受体基团取代，包括-N02，-N(烷基)3，-CF3，CC13，-CN，-COOH，-COOAlk，-COOAr，-CHO，-COAlk，-COAr，-F，-CI，-Br，-I，和/或电子供体基团包括-NH2，-NHalkyl，-N(alkyl)2，-OH，-Oalkyl，-Oaryl，-NHCOCH3，-NHCOalkyl；-NHCOaryl；-烷基，-芳基，其中当R1和R3是-N02，那么R2是R4是-H，或者当R1和R3是-H，那么R2和R4是-N02。这些化合物可以通过简单的合成法制备，并且具有低毒性和对包括多药耐药株在内的分枝杆菌的显著活性。本发明还提供了一种以通式(I)的取代二唑作为活性成分的药物制剂，以及将这种取代二唑用作抗结核药的应用。

  公开号：

  WO2014161516A1

文献信息

• [EN] OXA- AND THIA-DIAZOLES USEFUL IN THE TREATMENT OF TUBERCULOSIS<br/>[FR] OXADIAZOLES ET THIADIAZOLES UTILES DANS LE TRAITEMENT DE LA TUBERCULOSE
  申请人：UNIVERZITA KARLOVA V PRAZE FARMACEUTICKA FAKULTA V HRADCI KRALOVE

  公开号：WO2014161516A1

  公开（公告）日：2014-10-09

  A substituted diazole of genera l formula (1) wherein X is 0 or S; R is selected from the group consisting of: H, NH2-, C1-C11n alkyl, cyclohexyl-, benzyl-, phenyl-, pyridyl- or phenyl- substituted, in positions 2, 3, 4 or 5, by one or more electron-acceptor groups comprising -N02, -N(a lkyl)3, -CF3, CC13, -CN, -COOH, -COOAlk, -COOAr, -CHO, -COAlk, -COAr, -F, -CI, -Br, -I, and/or electron-donor groups comprising -NH2, -N Halkyl, -N(alkyl)2, -OH, -Oalkyl, -Oaryl, -NHCOCH3, -NHCOalkyl; -NHCOaryl; -alkyl, -aryl, wherein when R1 and R3 is -N02, then R2 a R4 is -H, or when R1 and R3 is -H, then R2 and R4 is -N02. These compounds can be prepared by easy synthesis and have low toxicity and significant activity against mycobacteria including their multiresistant strains. The invention provides also a pharmaceutical preparation having substituted diazole of formula (I) as the active ingredient, as well as the use of this substituted diazole as antituberculotic.

  一种通式(1)的取代二唑，其中X是0或S；R选自包括以下组：H，NH2-，C1-C11n烷基，环己基-，苄基-，苯基-，吡啶基-或苯基-，在2、3、4或5的位置上，被一个或多个电子受体基团取代，包括-N02，-N(烷基)3，-CF3，CC13，-CN，-COOH，-COOAlk，-COOAr，-CHO，-COAlk，-COAr，-F，-CI，-Br，-I，和/或电子供体基团包括-NH2，-NHalkyl，-N(alkyl)2，-OH，-Oalkyl，-Oaryl，-NHCOCH3，-NHCOalkyl；-NHCOaryl；-烷基，-芳基，其中当R1和R3是-N02，那么R2是R4是-H，或者当R1和R3是-H，那么R2和R4是-N02。这些化合物可以通过简单的合成法制备，并且具有低毒性和对包括多药耐药株在内的分枝杆菌的显著活性。本发明还提供了一种以通式(I)的取代二唑作为活性成分的药物制剂，以及将这种取代二唑用作抗结核药的应用。
• 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.