N-2-<4(5)-imidazolyl>ethylthiourea | 33550-78-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-2-<4(5)-imidazolyl>ethylthiourea
• 英文别名: [2-(1(3)H-imidazol-4-yl)-ethyl]-thiourea；N-<2-(4(5)-Imidazolyl)-ethyl>-thioharnstoff；N-<2-(4-imidazolyl)ethyl>thioharnstoff；N-[2-(1H-imidazol-5-yl)ethyl]thiourea；2-(1H-imidazol-5-yl)ethylthiourea
• CAS: 33550-78-6
• 化学式: C₆H₁₀N₄S
• 分子量: 170.238
• InChiKey: YWNWQKFEUQDKSB-UHFFFAOYSA-N

物化性质

• 沸点：
  444.9±47.0 °C(Predicted)
• 密度：
  1.332±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  98.8
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 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-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

• Novel piperidine derivative
  申请人：Ohtake Norikazu

  公开号：US20070105901A1

  公开（公告）日：2007-05-10

  Provided are a histamine-H3 receptor antagonist; and a preventive and/or a remedy for metabolic system diseases such as obesity, diabetes, hormone secretion disorder, hyperlipemia, gout, fatty liver, circulatory system diseases, for example, stenocardia, acute/congestive cardiac insufficiency, cardiac infarction, coronary arteriosclerosis, hypertension, nephropathy, sleep disorder and various diseases accompanied by sleep disorder such as idiopathic hypersomnia, repetitive hypersomnia, true hypersomnia, narcolepsy, sleep periodic acromotion disorder, sleep apnea syndrome, circadian rhythm disorder, chronic fatigue syndrome, REM sleep disorder, senile insomnia, night worker sleep insanitation, idiopathic insomnia, repetitive insomnia, true insomnia, electrolyte metabolism disorder, and central and peripheral nervous system diseases such as bulimia, emotional disorder, melancholia, anxiety, epilepsy, delirium, dementia, shinzophrenia, attention deficit/hyperactivity disorder, memory disorder, Alzheimer's disease, Parkinson's disease, sleep disorder, recognition disorder, motion disorder, paresthesia, dysosmia, epilepsy, morphine resistance, narcotic dependency, alcoholic dependency. The histamine-H3 receptor antagonist comprises a piperidine derivative compound of formula (I) [wherein X 1 and X 2 independently represent a nitrogen atom or CH; Y represents a specific group; X 3 represents O s —(CH 2 ) m ; R 1 and R 2 independently represent a hydrogen atom, a halogen atom, a linear or branched lower alkyl group, a lower alkoxy group, or an acetyl group substituted with 2 or 3 fluorine atoms; s is 0 or 1; and m is an integer to make (m+s) 0 or from 1 to 4], or its pharmaceutically-acceptable salt.

  本发明提供了一种组胺H3受体拮抗剂；以及预防和/或治疗代谢系统疾病，例如肥胖症、糖尿病、激素分泌障碍、高脂血症、痛风、脂肪肝、循环系统疾病，例如心绞痛、急性/充血性心力衰竭、心肌梗塞、冠状动脉硬化、高血压、肾病、睡眠障碍以及伴随着睡眠障碍的各种疾病，例如特发性嗜睡症、反复性嗜睡症、真性嗜睡症、嗜睡症、睡眠周期性运动障碍、睡眠呼吸暂停综合征、昼夜节律障碍、慢性疲劳综合征、REM睡眠障碍、老年失眠、夜班工人睡眠不卫生、特发性失眠、反复性失眠、真性失眠、电解质代谢障碍，以及中枢和外周神经系统疾病，例如贪食症、情绪障碍、忧郁症、焦虑症、癫痫、谵妄、痴呆、精神分裂症、注意力缺陷/多动障碍、记忆障碍、阿尔茨海默病、帕金森病、睡眠障碍、认知障碍、运动障碍、感觉异常、嗅觉障碍、癫痫、吗啡耐受、麻醉剂依赖、酒精依赖等的预防和/或治疗剂。该组胺H3受体拮抗剂包括式（I）的哌啶衍生物化合物[其中X1和X2独立地表示氮原子或CH；Y表示特定基团；X3表示Os—（CH2）m；R1和R2独立地表示氢原子、卤素原子、线性或支链低碳基、低碳氧基或2或3个氟原子取代的乙酰基；s为0或1；m是一个使（m+s）为0或1至4的整数]或其药学上可接受的盐。
• 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.
• PIPERIDINE DERIVATIVES
  申请人：MSD K.K.

  公开号：EP1669350B1

  公开（公告）日：2012-02-29
• US7547693B2
  申请人：——

  公开号：US7547693B2

  公开（公告）日：2009-06-16
• US7834182B2
  申请人：——

  公开号：US7834182B2

  公开（公告）日：2010-11-16