N-benzoyl-N'-2-<4(5)-imidazolyl>ethylthiourea | 33550-76-4

• 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: N-benzoyl-N'-2-<4(5)-imidazolyl>ethylthiourea
• 英文别名: 1-benzoyl-3-[2-(1H-imidazol-4-yl)-ethyl]-thiourea；N-[2-(1H-imidazol-5-yl)ethylcarbamothioyl]benzamide
• CAS: 33550-76-4
• 化学式: C₁₃H₁₄N₄OS
• 分子量: 274.346
• InChiKey: OKPWXSMQVRRQJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-benzoyl-N'-2-<4(5)-imidazolyl>ethylthiourea 在 sodium carbonate 作用下， 反应 1.0h， 生成 N-2-<4(5)-imidazolyl>ethylthiourea
  参考文献：
  名称：

  Heteroarylaminoethyl and heteroarylthioethyl imidazoles. Synthesis and H3-receptor affinity

  摘要：

  The synthesis of new H-3-receptor antagonists, 4-(2-heteroarylaminoethyl) and 4-(2-heteroarylthioethyl) imidazoles and their H-3-receptor affinity obtained from competitive binding curves vs [H-3]-N-alpha-methylhistamine ([H-3]NAMHA) on rat brain cortex membranes are described. These compounds are derived from structural modulations of thioperamide and were synthesized in order to study binding interactions with H-3-receptors and find alternative lead compounds with H-3-receptor antagonist activity. The new compounds differ from thioperamide by the following features: 1) the N-cyclohexylcarbothioamide moiety of thioperamide has been replaced by a benzothiazole (1); 2) the piperidine ring has been replaced by more flexible aminoethyl and thioethyl chains, in order to lower the excessive rigidity of 1 and to test the importance of the tertiary piperidine nitrogen; and 3) the benzothiazole moiety of 1 has been replaced by other heterocyclic nuclei, endowed with different lipophilic, steric and hydrogen-bonding features. Some of the compounds tested showed good affinity for central H-3-receptors (pK(i) range: 5.89-7.96) and can be considered as lead compounds for further optimization studies. The most lipophilic compounds showed higher affinities among benzo-condensed compounds, while imidazolylthioethyl imidazoles were more potent in displacing [H-3]NAMHA than thiazolylthioethyl and thiazolylaminoethyl imidazoles which suggests an interaction between the annular NH of the imidazolylthioethyl moiety and the binding site.

  DOI：

  10.1016/0223-5234(96)88307-3
• 作为产物：
  描述：

  组胺 在 盐酸 、 一水合肼 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 甲苯 、 乙腈 为溶剂， 反应 12.0h， 生成 N-benzoyl-N'-2-<4(5)-imidazolyl>ethylthiourea
  参考文献：
  名称：

  碳酸酐酶激活剂-第21部分。结合了羧酰胺基和脲基组胺部分的同工酶I，II和IV的新型激活剂。

  摘要：

  组胺与四溴邻苯二甲酸酐反应，并用三苯甲基磺酰氯保护其咪唑部分，然后进行肼解反应，得到N-1-三苯甲基磺酰组胺，其为关键中间体，其氨基乙基部分进一步衍生。通过在碳二亚胺存在下使关键中间体与羧酸酐，酰氯或羧酸反应获得羧酰胺衍生物。相同的关键中间体与异氰酸酯，异硫氰酸酯，氰酰胺或双氰胺反应，得到另一系列化合物。在二恶烷中用盐酸使上述中间体脱保护，得到两个系列的化合物，即在分子中具有羧酰胺基，脲基，硫脲基或胍基部分的组胺衍生物。分析了新衍生物作为三种碳酸酐酶（CA）同工酶的激活剂，hCA I，hCA II（胞质形式）和bCA IV（膜结合形式，h =人，b =牛同工酶）。观察到针对所有三种同工酶的有效活化，尤其是针对hCA I和bCA IV的活化，其最佳化合物的亲和力在纳摩尔范围内。另一方面，hCA II可以以约10-25 nM的亲和力激活。这类新型的CA激活剂可能导致针对CA缺乏综合症（一种骨骼

  DOI：

  10.1016/s0223-5234(00)00102-1

文献信息

• Carbonic anhydrase activators – Part 21. Novel activators of isozymes I, II and IV incorporating carboxamido and ureido histamine moieties
  作者：A Scozzafava

  DOI：10.1016/s0223-5234(00)00102-1

  日期：2000.1

  carboxylic acids in the presence of carbodiimides. Reaction of the same key intermediate with isocyanates, isothiocyanates, cyanamide or dicyandiamide afforded another series of compounds. Deprotection of the above-mentioned intermediates with hydrochloric acid in dioxane afforded two series of compounds, histamine derivatives possessing carboxamido, ureido, thioureido or guanidino moieties in their molecule

  组胺与四溴邻苯二甲酸酐反应，并用三苯甲基磺酰氯保护其咪唑部分，然后进行肼解反应，得到N-1-三苯甲基磺酰组胺，其为关键中间体，其氨基乙基部分进一步衍生。通过在碳二亚胺存在下使关键中间体与羧酸酐，酰氯或羧酸反应获得羧酰胺衍生物。相同的关键中间体与异氰酸酯，异硫氰酸酯，氰酰胺或双氰胺反应，得到另一系列化合物。在二恶烷中用盐酸使上述中间体脱保护，得到两个系列的化合物，即在分子中具有羧酰胺基，脲基，硫脲基或胍基部分的组胺衍生物。分析了新衍生物作为三种碳酸酐酶（CA）同工酶的激活剂，hCA I，hCA II（胞质形式）和bCA IV（膜结合形式，h =人，b =牛同工酶）。观察到针对所有三种同工酶的有效活化，尤其是针对hCA I和bCA IV的活化，其最佳化合物的亲和力在纳摩尔范围内。另一方面，hCA II可以以约10-25 nM的亲和力激活。这类新型的CA激活剂可能导致针对CA缺乏综合症（一种骨骼
• Heteroarylaminoethyl and heteroarylthioethyl imidazoles. Synthesis and H3-receptor affinity
  作者：P.V. Plazzi、F Bordi、M Mor、C Silva、G Morini、A Caretta、E Barocelli、T Vitali

  DOI：10.1016/0223-5234(96)88307-3

  日期：1995.1

  The synthesis of new H-3-receptor antagonists, 4-(2-heteroarylaminoethyl) and 4-(2-heteroarylthioethyl) imidazoles and their H-3-receptor affinity obtained from competitive binding curves vs [H-3]-N-alpha-methylhistamine ([H-3]NAMHA) on rat brain cortex membranes are described. These compounds are derived from structural modulations of thioperamide and were synthesized in order to study binding interactions with H-3-receptors and find alternative lead compounds with H-3-receptor antagonist activity. The new compounds differ from thioperamide by the following features: 1) the N-cyclohexylcarbothioamide moiety of thioperamide has been replaced by a benzothiazole (1); 2) the piperidine ring has been replaced by more flexible aminoethyl and thioethyl chains, in order to lower the excessive rigidity of 1 and to test the importance of the tertiary piperidine nitrogen; and 3) the benzothiazole moiety of 1 has been replaced by other heterocyclic nuclei, endowed with different lipophilic, steric and hydrogen-bonding features. Some of the compounds tested showed good affinity for central H-3-receptors (pK(i) range: 5.89-7.96) and can be considered as lead compounds for further optimization studies. The most lipophilic compounds showed higher affinities among benzo-condensed compounds, while imidazolylthioethyl imidazoles were more potent in displacing [H-3]NAMHA than thiazolylthioethyl and thiazolylaminoethyl imidazoles which suggests an interaction between the annular NH of the imidazolylthioethyl moiety and the binding site.