8-azabicyclo[3.2.1]oct-3-yl 2-phenylcyclohex-2-enecarboxylate | 675868-81-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 8-azabicyclo[3.2.1]oct-3-yl 2-phenylcyclohex-2-enecarboxylate
• CAS: 675868-81-2
• 化学式: C₂₀H₂₅NO₂
• 分子量: 311.424
• InChiKey: PJCCMHKPDZBEBK-RKRXFFETSA-N

物化性质

• 沸点：
  442.3±45.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  8-azabicyclo[3.2.1]oct-3-yl 2-phenylcyclohex-2-enecarboxylate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 35.0h， 生成 ethyl 2-[8-aza-exo-8-methyl-3-(2-phenylcyclohex-2-enylcarbonyloxy)bicyclo[3.2.1]oct-8-yl]acetate, methyl hydroxysulfonate
  参考文献：
  名称：

  摘要：

  Purpose. To design and evaluate a new class of soft anticholinergics with subtype selectivity.Methods. A new class of soft anticholinergics was designed based on the "inactive metabolite" approach. Four compounds were synthesized. The potency and soft nature of the compounds were evaluated by receptor binding, cardiac, and mydriatic studies. Stability and pharmacokinetic studies were also performed on these newly synthesized soft anticholinergics.Results. Receptor binding studies of the soft anticholinergics on cloned muscarinic receptors indicated pKi values in the range of 7.5 to 8.9. Two compounds, 9a and 13a, of the series showed muscarinic subtype receptor selectivity (M-3/M-2). In mydriatic studies, 13a and 13b showed shorter duration of action in the treated eyes than tropicamide. In the control eyes, significant dilation of pupils was found only in rabbits treated with atropine and tropicamide, indicating that the soft anticholinergics lack systemic effects because of their facile hydrolytic deactivation. Consistent with their soft nature, this new class of soft anticholinergics displayed much shorter cardiovascular effects in the carbachol-induced bradycardia (10 to 15 min) in rats than atropine (>60 min). Stability and pharmacokinetic studies suggested that the new soft anticholinergics were rapidly eliminated from plasma (systemic circulation) after i.v. administration.Conclusions. A new class of anticholinergics was designed and synthesized, and the PK/PD evaluation confirmed they were potent "soft" anticholinergics; two of them showed muscarinic receptor subtype selectivity (M-3/M-2).

  DOI：

  10.1023/a:1026160023030
• 作为产物：
  描述：

  2-phenyl-2-cyclohexene-1-carbonyl chloride 以 甲醇 、 1,2-二氯乙烷 为溶剂， 反应 1.75h， 生成 8-azabicyclo[3.2.1]oct-3-yl 2-phenylcyclohex-2-enecarboxylate
  参考文献：
  名称：

  摘要：

  Purpose. To design and evaluate a new class of soft anticholinergics with subtype selectivity.Methods. A new class of soft anticholinergics was designed based on the "inactive metabolite" approach. Four compounds were synthesized. The potency and soft nature of the compounds were evaluated by receptor binding, cardiac, and mydriatic studies. Stability and pharmacokinetic studies were also performed on these newly synthesized soft anticholinergics.Results. Receptor binding studies of the soft anticholinergics on cloned muscarinic receptors indicated pKi values in the range of 7.5 to 8.9. Two compounds, 9a and 13a, of the series showed muscarinic subtype receptor selectivity (M-3/M-2). In mydriatic studies, 13a and 13b showed shorter duration of action in the treated eyes than tropicamide. In the control eyes, significant dilation of pupils was found only in rabbits treated with atropine and tropicamide, indicating that the soft anticholinergics lack systemic effects because of their facile hydrolytic deactivation. Consistent with their soft nature, this new class of soft anticholinergics displayed much shorter cardiovascular effects in the carbachol-induced bradycardia (10 to 15 min) in rats than atropine (>60 min). Stability and pharmacokinetic studies suggested that the new soft anticholinergics were rapidly eliminated from plasma (systemic circulation) after i.v. administration.Conclusions. A new class of anticholinergics was designed and synthesized, and the PK/PD evaluation confirmed they were potent "soft" anticholinergics; two of them showed muscarinic receptor subtype selectivity (M-3/M-2).

  DOI：

  10.1023/a:1026160023030