2-(5,6,7,8-tetrahydro-naphthalen-2-ylimino)-imidazolidine-1,3-dicarboxylic acid di-tert-butyl ester | 1029802-04-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 2-(5,6,7,8-tetrahydro-naphthalen-2-ylimino)-imidazolidine-1,3-dicarboxylic acid di-tert-butyl ester
• 英文别名: 2-(5,6,7,8-tetrahydro-naphthelen-2-ylimino)-imidazolidine-1,3-dicarboxylic acid di-tert-butyl ester；Ditert-butyl 2-(5,6,7,8-tetrahydronaphthalen-2-ylimino)imidazolidine-1,3-dicarboxylate
• CAS: 1029802-04-7
• 化学式: C₂₃H₃₃N₃O₄
• 分子量: 415.533
• InChiKey: QRMZWZKAFCNZSJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  71.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(5,6,7,8-tetrahydro-naphthalen-2-ylimino)-imidazolidine-1,3-dicarboxylic acid di-tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 27.0h， 以94%的产率得到imidazolidin-2-ylidene-(5,6,7,8-tetrahydronaphthalen-2-yl)amine hydrochloride
  参考文献：
  名称：

  Guanidine and 2-Aminoimidazoline Aromatic Derivatives as α₂-Adrenoceptor Antagonists. 2. Exploring Alkyl Linkers for New Antidepressants

  摘要：

  The preparation of a number of (bis)ouanidine and (bis)2-aminoimidazoline derivatives as potential alpha(2)-adrenoceptor antagonists for the treatment of depression is presented. Human brain tissue was used to measure their affinity toward the alpha(2)-adrenoceptors in vitro. Compounds 6b, 8b, 9b, 10b, 15b, 17b, 18b, 20b, and 21b displayed a good affinity (pK(i) > 7) and were evaluated in in vitro functional [(35)S]GTP gamma S binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Among these compounds, 17b and 20b showed the expected behavior for an antagonist and were subject to in vivo microdialysis experiments in rats. Significantly, these experiments confirmed the antagonistic properties of 17b and 20b, and therefore both compounds can be considered as potential antidepressants.

  DOI：

  10.1021/jm800026x
• 作为产物：
  描述：

  5,6,7,8-四氢-2-萘胺 、 2-thioxo-imidazolidine-1,3-dicarboxylic acid di-tert-butyl ester 在 三乙胺 、 mercury dichloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(5,6,7,8-tetrahydro-naphthalen-2-ylimino)-imidazolidine-1,3-dicarboxylic acid di-tert-butyl ester
  参考文献：
  名称：

  取代基对芳基胍和2-（芳基）亚咪唑烷的碱度（p K a）的影响：pH值和UV值与气相从头算键长预测的相关性

  摘要：

  的两个相关系列2-（芳基亚氨基）咪唑烷和芳基胍α的解离常数2 -肾上腺素能受体拮抗剂（化合物35总共）通过电势滴定，并通过使用96孔微量滴定板方法紫外分光光度法测定。使用这两种方法获得的实验值是非常一致的，并且与使用AIBLHiCoS方法计算的p K a值非常吻合，该方法仅使用了从头算的低理论水平获得的单键长度。咪唑烷和胍组化合物的预测能力非常好，偏差通常<0.30和<0.24 p K a单位，平均绝对误差（MAE）分别为0.23和0.29。研究各种取代基对芳基胍和2-（芳基氨基）咪唑烷衍生物的碱性的定量作用的研究对从事与生物学相关的含胍分子的药物化学家是有用的。

  DOI：

  10.1039/c7nj02497e

文献信息

• GUANIDINE BASED COMPOUNDS
  申请人：Rozas Hernando Maria Isabel

  公开号：US20100331384A1

  公开（公告）日：2010-12-30

  The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into α and β subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of a number of diseases. Disclosed herein are a series of novel guanidine and 2-aminoimidazoline compounds which are ligands of the alpha2-adrenoceptor (α2-ARs) subclass of adrenergic receptors. The invention also provides for pharmaceutical compositions comprising the novel compounds. The compounds are suitable for use in the manufacture of medicaments for the treatment of α2-ARs associated disorders, such as depression, schizophrenia, glaucoma and analgesia.

  肾上腺素受体或肾上腺素受体是一类G蛋白偶联受体家族，分为α和β亚类。肾上腺素受体在调节多种生理条件中起着重要作用，其功能失调已被认为与多种疾病的病理生理有关。本文披露了一系列新型胍啶和2-氨基咪唑啉化合物，它们是肾上腺素受体的α2-亚型（α2-ARs）亚类的配体。该发明还提供了包含这些新型化合物的药物组合物。这些化合物适用于制造用于治疗与α2-ARs相关疾病的药物，如抑郁症、精神分裂症、青光眼和镇痛的药物。
• [EN] GUANIDINE BASED COMPOUNDS<br/>[FR] COMPOSÉS À BASE DE GUANIDINE
  申请人：TRINITY COLLEGE DUBLIN

  公开号：WO2009080818A2

  公开（公告）日：2009-07-02

  The adrenergic receptors or adrenoceptors are a family of G-protein coupled receptors split into α and β subclasses. The adrenoceptors have important roles in regulating a myriad of physiological conditions and their malfunction has been implicated in the pathophysiology of anumber of diseases. Disclosed herein are a series of novel guanidine and 2-aminoimidazoline compounds which are ligands of the alpha2- adrenoceptor (α2-ARs) subclass of adrenergic receptors. The invention also provides for pharmaceutical compositions comprising the novel compounds. The compounds are suitable for use in the manufacture of medicaments for the treatment of α2-ARs associated disorders, such as depression, schizophrenia, glaucoma and analgesia.
• Substituent effects on the basicity (pK_a) of aryl guanidines and 2-(arylimino)imidazolidines: correlations of pH-metric and UV-metric values with predictions from gas-phase ab initio bond lengths
  作者：Christophe Dardonville、Beth A. Caine、Marta Navarro de la Fuente、Guillermo Martín Herranz、Beatriz Corrales Mariblanca、Paul L. A. Popelier

  DOI：10.1039/c7nj02497e

  日期：——

  compounds was very good with deviations typically <0.30 and <0.24 pKa units, and a mean absolute error (MAE) of 0.23 and 0.29, respectively. The study of the quantitative effect of diverse substituents on the basicity of aryl guanidine and 2-(arylimino)imidazolidine derivatives is useful for medicinal chemists working with biologically relevant guanidine-containing molecules.

  的两个相关系列2-（芳基亚氨基）咪唑烷和芳基胍α的解离常数2 -肾上腺素能受体拮抗剂（化合物35总共）通过电势滴定，并通过使用96孔微量滴定板方法紫外分光光度法测定。使用这两种方法获得的实验值是非常一致的，并且与使用AIBLHiCoS方法计算的p K a值非常吻合，该方法仅使用了从头算的低理论水平获得的单键长度。咪唑烷和胍组化合物的预测能力非常好，偏差通常<0.30和<0.24 p K a单位，平均绝对误差（MAE）分别为0.23和0.29。研究各种取代基对芳基胍和2-（芳基氨基）咪唑烷衍生物的碱性的定量作用的研究对从事与生物学相关的含胍分子的药物化学家是有用的。
• Guanidine and 2-Aminoimidazoline Aromatic Derivatives as α₂-Adrenoceptor Antagonists. 2. Exploring Alkyl Linkers for New Antidepressants
  作者：Fernando Rodriguez、Isabel Rozas、Jorge E. Ortega、Amaia M. Erdozain、J. Javier Meana、Luis F. Callado

  DOI：10.1021/jm800026x

  日期：2008.6.1

  The preparation of a number of (bis)ouanidine and (bis)2-aminoimidazoline derivatives as potential alpha(2)-adrenoceptor antagonists for the treatment of depression is presented. Human brain tissue was used to measure their affinity toward the alpha(2)-adrenoceptors in vitro. Compounds 6b, 8b, 9b, 10b, 15b, 17b, 18b, 20b, and 21b displayed a good affinity (pK(i) > 7) and were evaluated in in vitro functional [(35)S]GTP gamma S binding assays in human prefrontal cortex to determine their agonistic or antagonistic activity. Among these compounds, 17b and 20b showed the expected behavior for an antagonist and were subject to in vivo microdialysis experiments in rats. Significantly, these experiments confirmed the antagonistic properties of 17b and 20b, and therefore both compounds can be considered as potential antidepressants.