2-{[2-(1H-Imidazol-4-yl)ethyl]amino}benzothiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-{[2-(1H-Imidazol-4-yl)ethyl]amino}benzothiazole
• 英文别名: Benzothiazol-2-yl-[2-(1H-imidazol-4-yl)-ethyl]-amine；N-[2-(1H-imidazol-5-yl)ethyl]-1,3-benzothiazol-2-amine
• 化学式: C₁₂H₁₂N₄S
• 分子量: 244.32
• InChiKey: CMRUWLLBGWHPSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氯苯并噻唑 、 histamine dichloride 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以62%的产率得到2-{[2-(1H-Imidazol-4-yl)ethyl]amino}benzothiazole
  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differ from thioperamide by the following features: 1) the N-cyclohexylcarbothioamide moiety of thioperamide has been replaced by a benzothiazole (1); 2) the piperidine ring has been replaced by more flexible aminoethyl and thioethyl chains, in order to lower the excessive rigidity of 1 and to test the importance of the tertiary piperidine nitrogen; and 3) the benzothiazole moiety of 1 has been replaced by other heterocyclic nuclei, endowed with different lipophilic, steric and hydrogen-bonding features.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

文献信息

• Imidazole compounds and their therapeutic applications
  申请人：Institut National de la Sante et de la Recherche Medicale

  公开号：US05559113A1

  公开（公告）日：1996-09-24

  A compound selected from the group consisting of a compound of the formula ##STR1## wherein the substituents are defined as in the specification having antagonist properties to histamine H.sub.3 -receptors.

  从以下化合物组合中选择的一种化合物，其化学式为##STR1##其中取代基的定义如规范中所述，具有对组织胺H.sub.3受体的拮抗性能。
• Design of Potent Non-Thiourea H3-Receptor Histamine Antagonists
  作者：C. Robin Ganellin、S. Kiumars Hosseini、Yasmin S. Khalaf、Wasyl Tertiuk、Jean-Michel Arrang、Monique Garbarg、Xavier Ligneau、Jean-Charles Schwartz

  DOI：10.1021/jm00017a018

  日期：1995.8

  Starting from thioperamide, the first potent and selective H3-receptor histamine antagonist, analogues have been synthesized and tested in vitro on rat cerebral cortex to explore structure-activity relationships. The aim has been to design potent compounds which do not possess the thiourea group of thioperamide and which may have improved brain penetration. In a short series of open chain thiourea

  从第一个有效的选择性H3受体组胺拮抗剂thioperamide开始，已经合成了类似物，并在大鼠大脑皮质进行了体外测试，以探索其结构活性之间的关系。目的是设计不具有硫代过酰胺的硫脲基团并且可以改善脑渗透性的有效化合物。在短系列的开链硫脲类似物中，发现H3拮抗剂效能的最佳链长为（CH2）3。衍生自组胺并在侧链氨基上具有芳族含氮杂环而不是硫脲的化合物具有H3拮抗活性。此外，当杂环为2-吡啶基时，吡啶5-位上的吸电子取代基（例如NO 2，CF 3，CO 2 Me）增加了效力。描述了4- [4（5）-咪唑基]哌啶的合成及其向硫代过酰胺的（三氟甲基）吡啶基类似物5b的转化。然而，5b不如硫代过酰胺强。用吡啶取代咪唑或在远处的N上取代咪唑会大大降低效力。用S取代侧链NH进一步提高了效力，最有效的化合物是2-（[2- [4（5）-咪唑基]乙基]硫基] -5-硝基吡啶（UCL 1199），其Ki = 4.8
• NOUVEAUX DERIVES DE L'IMIDAZOLE, LEUR PREPARATION ET LEURS APPLICATIONS THERAPEUTIQUES
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP0597088A1

  公开（公告）日：1994-05-18
• US5559113A
  申请人：——

  公开号：US5559113A

  公开（公告）日：1996-09-24
• US5708171A
  申请人：——

  公开号：US5708171A

  公开（公告）日：1998-01-13