3-(3-chloro-1,4-diazin-2-yl)-1-azabicyclo<2.2.1>heptan-3-ol | 138449-64-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-(3-chloro-1,4-diazin-2-yl)-1-azabicyclo<2.2.1>heptan-3-ol
• 英文别名: 3-(3-Chloropyrazinyl)-1-azabicyclo[2.2.1]heptan-3-ol；3-(3-chloropyrazin-2-yl)-1-azabicyclo[2.2.1]heptan-3-ol
• CAS: 138449-64-6
• 化学式: C₁₀H₁₂ClN₃O
• 分子量: 225.678
• InChiKey: YMLBHEFZZMVIKC-UHFFFAOYSA-N

物化性质

• 沸点：
  381.4±42.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  49.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3-chloro-1,4-diazin-2-yl)-1-azabicyclo<2.2.1>heptan-3-ol 在 palladium on activated charcoal 氯化亚砜 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 80.0 ℃ 、413.69 kPa 条件下， 反应 2.5h， 生成 exo-3-<3-(hexyloxy)pyrazinyl>-1-azabicyclo<2.2.1>heptane
  参考文献：
  名称：

  Functionally selective M1 muscarinic agonists. 3. Side chain and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles

  摘要：

  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.

  DOI：

  10.1021/jm00018a007
• 作为产物：
  描述：

  2-氯吡嗪 、 1-氮杂双环[2.2.1]庚烷-3-酮 在 2,2,6,6-四甲基哌啶 、 正丁基锂 作用下， 生成 3-(3-chloro-1,4-diazin-2-yl)-1-azabicyclo<2.2.1>heptan-3-ol
  参考文献：
  名称：

  Functionally selective M1 muscarinic agonists. 3. Side chain and azacycles contributing to functional muscarinic selectivity among pyrazinylazacycles

  摘要：

  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.

  DOI：

  10.1021/jm00018a007

文献信息

• Heterocyclic compounds their preparation and use
  申请人：Novo Nordisk A/S

  公开号：US05182283A1

  公开（公告）日：1993-01-26

  The present invention relates to therapeutically active azacyclic or azabicyclic compounds, a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful as stimulants of the cognitive function of the forebrain and hippocampus of mammals and especially in the treatment of Alzheimer's disease.

  本发明涉及治疗活性的杂环或氮杂双环化合物，一种制备方法以及包含这些化合物的药物组合物。这些新颖的化合物可用作刺激哺乳动物前脑和海马的认知功能的药物，特别适用于治疗阿尔茨海默病。
• AZACYCLIC OR AZABICYCLIC COMPOUNDS, THEIR PREPARATION AND USE
  申请人：NOVO NORDISK A/S

  公开号：EP0521067B1

  公开（公告）日：1995-06-28
• US5182283A
  申请人：——

  公开号：US5182283A

  公开（公告）日：1993-01-26
• [EN] AZACYCLIC OR AZABICYCLIC COMPOUNDS, THEIR PREPARATION AND USE
  申请人：——

  公开号：WO1991014686A1

  公开（公告）日：1991-10-03

  [FR] L'invention concerne des composés azacycliques ou azabicycliques thérapeutiquement actifs de formule (I), un procédé de préparation de ces composés et des compositions pharmaceutiques qui en contiennent. Ces nouveaux composés sont utilisés comme stimulants de la fonction cognitive du cerveau antérieur et de l'hippocampe des mammifères, et notamment dans le traitement de la maladie d'Alzheimer. (A), (B) ou (C), où R et R1 sont tels qu'ils sont définis dans la revendication.
  [EN] The present invention relates to therapeutically active azacyclic or azabicyclic compounds of formula (I), a method of preparing the same and to pharmaceutical compositions comprising the compounds. The novel compounds are useful as stimulants of the cognitive function of the forebrain and hippocampus of mammals and especially in the treatment of Alzheimer's disease. (A), (B) or (C), wherein R and R?1 are as defined in claim 1.
• 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.