3-(1,4-diazin-2-yl)-1-azabicyclo<2.2.2>octane | 125059-50-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 英文名称: 3-(1,4-diazin-2-yl)-1-azabicyclo<2.2.2>octane
• 英文别名: 3-(2-pyrazinyl)-1-azabicyclo[2.2.2]octane；3-Pyrazin-2-yl-1-aza-bicyclo[2.2.2]octane；3-pyrazin-2-yl-1-azabicyclo[2.2.2]octane
• CAS: 125059-50-9
• 化学式: C₁₁H₁₅N₃
• 分子量: 189.26
• InChiKey: JNCZFHRKMBPTOW-UHFFFAOYSA-N

物化性质

• 沸点：
  312.9±27.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-奎宁环酮 在 palladium on activated charcoal 氯化亚砜 、 氢气 、 叔丁基锂 作用下， 以 乙醇 、 二氯甲烷 为溶剂， -35.0~25.0 ℃ 、344.73 kPa 条件下， 反应 6.25h， 生成 3-(1,4-diazin-2-yl)-1-azabicyclo<2.2.2>octane
  参考文献：
  名称：

  奎宁环烷基和（1-氮杂降冰片基）吡嗪衍生物的合成和毒蕈碱活性。

  摘要：

  描述了基于吡嗪的新型激动剂的合成和皮质毒蕈碱活性。通过锂化吡嗪与氮杂双环酮的反应，然后氯化和还原，或通过氮杂双环酯的烯醇锂与2-氯吡嗪的反应，然后酯水解和脱羧，来制备喹喔啶和金刚烷硼烷衍生物。已经研究了杂芳环的所有三个位置上的取代。对于金刚烷烷系列中未取代的吡嗪，观察到最佳的毒蕈碱激动剂活性。exo-1-azanorbornaneane 18a是已知的最有效和最有效的中枢活性毒蕈碱激动剂之一。对3-取代衍生物的研究提供了这些配体对于最佳毒蕈碱活性的优选构象的证据。在C6处取代使配体具有增加的亲和力和降低的功效。移动二嗪环氮的位置以得到嘧啶和哒嗪衍生物导致毒蕈碱活性的显着损失。

  DOI：

  10.1021/jm00080a014

文献信息

• Pyrazines, pyrimidines and pyridazines useful in the treatment of senile
  申请人：Merck Sharp & Dohme Limited

  公开号：US05260293A1

  公开（公告）日：1993-11-09

  The present invention provides pyrazines, pyridazines or pyrimidines, or salts or prodrugs thereof, substituted on one of the ring carbon atoms thereof with a non-aromatic azacyclic or azabicyclic ring system; and independently substituted on each of the other ring carbon atoms with a substituent of low lipophilicity or a hydrocarbon substituent; which compounds stimulate central muscarinic acetylcholine receptors and therefore are useful in the treatment of neurological and mental illnesses.

  本发明提供了吡啶、吡啶嗪或嘧啶，或其盐或前药，其中其中一个环碳原子上取代为非芳香性氮杂环或氮杂双环系统；并且独立地，在其他每个环碳原子上取代为低亲脂性取代基或烃取代基；这些化合物刺激中枢胆碱能受体，因此在治疗神经和精神疾病中是有用的。
• Synthesis of azabicyclic pyrazine derivatives as muscarinic agonists and the preparation of a chloropyrazine analogue with functional selectivity at sub-types of the muscarinic receptor
  作者：Raymond Baker、Leslie J. Street、Austin J. Reeve、John Saunders

  DOI：10.1039/c39910000760

  日期：——

  The synthesis of quinuclidine and azanorbornyl pyrazine derivatives has yielded highly potent and efficacious muscarinic agonists; chloro-substitution in the pyrazine ring of the quinuclidine analogue resulted in the formation of a derivative with both enantiomers displaying partial agonist character but, more importantly, functional selectivity at the M1, M2 and M3 sub-types of the muscarinic receptor

  奎尼丁和氮杂降冰片基吡嗪衍生物的合成已经产生了高效且有效的毒蕈碱激动剂。奎宁环类似物的吡嗪环中的氯取代导致形成具有两种对映异构体的衍生物，该对映异构体显示出部分激动剂特性，但更重要的是，在毒蕈碱受体的M 1，M 2和M 3亚型上具有功能选择性。
• Pyrazines, pyrimidines and pyridazines, useful in the treatment of senile dementia
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0327155A2

  公开（公告）日：1989-08-09

  The present invention provides pyrazines, pyridazines or pyrimidines, or salts or prodrugs thereof, substituted on one of the ring carbon atoms therefore with a non-aromatic azacyclic or azabicyclic ring system; and independently substituted on each of the other ring carbon atoms with a substituent of low lipophilicity or a hydrocarbon substituent; which compounds stimulate central muscarinic acetylcholine receptors and therefore are useful in the treatment of neurological and mental illnesses.

  本发明提供吡嗪类、哒嗪类或嘧啶类化合物，或其盐类或原药，其中一个环碳原子被非芳族氮杂环或氮杂环环系取代；其他每个环碳原子分别独立地被低亲脂性取代基或烃类取代基取代；这些化合物可刺激中枢毒蕈碱乙酰胆碱受体，因此可用于治疗神经和精神疾病。
• Functionally selective M1 muscarinic agonists. 3. Side chain and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles
  作者：John S. Ward、Leander Merrit、David O. Calligaro、Frank P. Bymaster、Harlan E. Shannon、Barry D. Sawyer、Charles H. Mitch、Jack B. Deeter、Steven C. Peters

  DOI：10.1021/jm00018a007

  日期：1995.9

  In an attempt to improve upon the M(1) agonist activity of the selective M(1) agonist xanomeline and related compounds, the M(1) muscarinic efficacies and potencies of 3- and 6-substituted pyrazinylazacycles were varied by changing both the 3- and 6-substituents as well as the azacycle. Significant improvements in efficacy and potency over the previously prepared [3-(hexyloxy)pyrazinyl]tetrahydropyridine 19 were obtained with the [3-(hexyloxy)pyrazinyl]quinuclidine 5i. The M(1) activity of 5i showed some enantioselectivity with (S)-5i being ca. 4-fold more potent than (R)-5i. Like 19 and xanomeline, 5i was a functionally selective M(1) agonist that showed greater functional selectivity than widely studied pyrazinylquinuclidine 5n (L-689,660). The improved functional selectivity of 5i over 5n could be attributed to the additional binding interactions between the hexyloxy side chain of 5i and the M(1) receptor that are not available to 5n. Although 5i may show M(1) functional selectivity comparable to xanomeliine, 5i is a less efficacious and potent M(1) agonist than xanomeline.
• US5260293A
  申请人：——

  公开号：US5260293A

  公开（公告）日：1993-11-09