Methyl 6-(3-hexoxypyrazin-2-yl)-2,3,4,7-tetrahydroazepine-1-carboxylate | 1026562-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: Methyl 6-(3-hexoxypyrazin-2-yl)-2,3,4,7-tetrahydroazepine-1-carboxylate
• CAS: 1026562-97-9
• 化学式: C₁₈H₂₇N₃O₃
• 分子量: 333.431
• InChiKey: CGUILXHRHOGZRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  64.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Methyl 6-(3-hexoxypyrazin-2-yl)-2,3,4,7-tetrahydroazepine-1-carboxylate 在 碘代三甲硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 3-<3-(hexyloxy)-1,4-diazin-2-yl>-2,5,6,7-tetrahydroazepine
  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：

  hexahydroazepin-3-one methylcarbamate 在 2,2,6,6-四甲基哌啶 、 正丁基锂 、 伯吉斯试剂 作用下， 以 甲苯 为溶剂， 反应 1.83h， 生成 Methyl 6-(3-hexoxypyrazin-2-yl)-2,3,4,7-tetrahydroazepine-1-carboxylate
  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