1-methyl-4,5-dipropylimidazole-2(3H)-thione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 1-methyl-4,5-dipropylimidazole-2(3H)-thione
• 英文别名: 3-methyl-4,5-dipropyl-1H-imidazole-2-thione
• 化学式: C₁₀H₁₈N₂S
• 分子量: 198.332
• InChiKey: ZZCXLPZEJWABEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  47.4
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  5-羟基-4-辛酮 、 N-甲硫脲 以 various solvent(s) 为溶剂， 反应 6.0h， 以42%的产率得到1-methyl-4,5-dipropylimidazole-2(3H)-thione
  参考文献：
  名称：

  1,4,5-三烷基咪唑体系的新型取代衍生物具有抗炎特性。

  摘要：

  在研究五元环含氮杂环化合物的抗炎特性时，通过改变取代位置并将脂肪链连接到咪唑的1位氮原子上，制备了咪唑的两个系列衍生物环。与消炎痛相比，它们中的一些是角叉菜胶诱发的水肿的更有效抑制剂。电子自旋共振研究表明这些化合物具有抗自由基活性。

  DOI：

  10.1248/cpb.42.698

文献信息

• 1,4,5-Trialkyl Imidazole System Anti-inflammatory Properties of New Substituted Derivatives.
  作者：Jamal FATIMI、Jean-Francois LAGORCE、Jean-Luc DUROUX、Marie-Laure CHABERNAUD、Jacques BUXERAUD、Claude RABY

  DOI：10.1248/cpb.42.698

  日期：——

  In an investigation of the anti-inflammatory properties of five-membered ring nitrogen-containing heterocyclic compounds, two series of derivatives of imidazole were prepared by altering the sites of substitution and by joining aliphatic chains to the nitrogen atom in the 1 position of the imidazole ring. Some of them were more potent inhibitors of carrageenan-induced edema than indomethacin. An electron

  在研究五元环含氮杂环化合物的抗炎特性时，通过改变取代位置并将脂肪链连接到咪唑的1位氮原子上，制备了咪唑的两个系列衍生物环。与消炎痛相比，它们中的一些是角叉菜胶诱发的水肿的更有效抑制剂。电子自旋共振研究表明这些化合物具有抗自由基活性。
• Fatimi; Lagorce; Chabernaud, Bollettino Chimico Farmaceutico, 1994, vol. 133, # 3, p. 151 - 155
  作者：Fatimi、Lagorce、Chabernaud、Buxeraud、Raby

  DOI：——

  日期：——
• Fatimi; Lagorce; Chabernaud, Il Farmaco, 1994, vol. 49, # 4, p. 253 - 257
  作者：Fatimi、Lagorce、Chabernaud、Comby、Buxeraud、Raby

  DOI：——

  日期：——
• Evidence for the Involvement of <i>N</i>-Methylthiourea, a Ring Cleavage Metabolite, in the Hepatotoxicity of Methimazole in Glutathione-Depleted Mice:  Structure−Toxicity and Metabolic Studies
  作者：Tamio Mizutani、Kaoru Yoshida、Mihoko Murakami、Mutsuko Shirai、Sadahiro Kawazoe

  DOI：10.1021/tx990155o

  日期：2000.3.1

  In mice depleted of GSH by treatment with buthionine sulfoximine (BSO), methimazole (2-mercapto-1-methylimidazole, MMI) causes liver injury characterized by centrilobular necrosis of hepatocytes and an increase in serum alanine transaminase (SALT) activity. MMI requires metabolic activation by both P450 monooxygenase and flavin-containing monooxygenase (FMO) before it produces the hepatotoxicity. MMI and its analogues were examined for the ability to increase SALT activity in GSH-depleted mice. Saturation of the C-4,ti double bond in MMI resulted in a complete loss of hepatotoxicity. Similarly, ring fusion of a benzene nucleus to the C-4,5 double bond, forming 2-mercapto-1-methylbenzimidazole, abolished the toxic potency. As for MMI, 2-mercapto-1,4,5-trimethylimidazole, and 2-mercapto-1-methyl-4,5-di-n-propylimidazole, the toxic potency decreased with the increasing bulk of the 4- and 5-alkyl substituents. Furthermore, methylation of the thiol group of MMI totally reduced its toxicity. These structural requirements and the known toxicity of thiono-sulfur compounds led us to the hypothesis that MMI would undergo epoxidation of the C-4,5 double bond by P450 enzymes and, after being hydrolyzed, the resulting epoxide would be then decomposed to form N-methylthiourea, a proximate toxicant. Before N-methylthiourea would produce toxicity, it would be further biotransformed to its S-oxidized metabolites mainly by FMO. Evidence for this hypothesis was provided by the facts that N-methylthiourea and glyoxal as the accompanying fragment were identified as urinary metabolites in mice treated with MMI and that N-methylthiourea caused a marked increase in SALT activity when administered to mice in combination with BSO.