S-(+)-alloecgonine (4-nitrophenyl)ethyl ester | 566198-61-6

• 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: S-(+)-alloecgonine (4-nitrophenyl)ethyl ester
• 英文别名: 2-(4-nitrophenyl)ethyl (1S,2S,3S,5R)-3-hydroxy-8-methyl-8-azabicyclo[3.2.1]octane-2-carboxylate
• CAS: 566198-61-6
• 化学式: C₁₇H₂₂N₂O₅
• 分子量: 334.372
• InChiKey: DDDUVGFYFKRIBT-UGUYLWEFSA-N

物化性质

• 沸点：
  497.6±45.0 °C(Predicted)
• 密度：
  1.297±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  95.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  S-(+)-alloecgonine (4-nitrophenyl)ethyl ester 在 palladium on activated charcoal 氢气 、 碳酸氢钠 、 对甲苯磺酸 作用下， 以 甲醇 、 氯仿 、 乙酸乙酯 、 苯 为溶剂， 反应 27.5h， 生成 S-(+)-2β-carbo(4-isothiocyanatophenyl)ethoxy-3α-(bis[4-fluorophenyl]methoxy)tropane
  参考文献：
  名称：

  Structure−Activity Relationship Comparison of (S)-2β-Substituted 3α-(Bis[4-fluorophenyl]methoxy)tropanes and (R)-2β-Substituted 3β-(3,4-Dichlorophenyl)tropanes at the Dopamine Transporter

  摘要：

  Extensive structure-activity relationships at the dopamine transporter (DAT) have been developed around two classes of tropane-based ligands. Opposing stereoselectivity and divergent structural requirements for optimal DAT binding suggest that these tropane-based DAT inhibitors may not access identical binding domains. To further investigate this hypothesis, a series of (S)-2beta-carboalkoxy-3alpha-(bis[4-fluorophenyl]methoxy)tropanes (11a-f, 13-16) and their identically (R)-2beta-substituted 3beta-(3,4-dichlorophenyl)tropanes (3, 5a-d) were prepared and evaluated for binding at the DAT and for inhibition of [H-3]dopamine uptake in rat brain. These studies showed that most of the identically 2-carboalkoxy-substituted analogues, within the two classes of compounds, bind with high affinity to DAT (K-i = 5.5 - 100 nM), albeit with opposite stereochemistry. However, the larger azido- (15) and isothiocyanato- (16) (S)-2beta-carbophenylethoxy-3alpha-(bis [4-fluorophenyl] methoxy)tropanes demonstrated a significant decrease in DAT binding potency (IC50 = 210 and 537 nM, respectively), suggesting that the DAT does not tolerate 2-position steric bulk in the benztropine class, as it does with the 2-substituted 3-aryltropanes. In addition, binding affinities at the serotonin transporter, norepinephrine transporter, and muscarinic receptors were evaluated and compared for compounds 2, 3, 11a-e, and 13. Together, the binding profiles across these systems demonstrated significant differences between these two classes of tropane-based ligands, which may be exploited toward the discovery of a cocaine-abuse pharmacotherapeutic.

  DOI：

  10.1021/jm0300375
• 作为产物：
  描述：

  S-(-)-carbomethoxytropinone 在 platinum(IV) oxide 盐酸 、 水 、 氢气 作用下， 以 乙醇 为溶剂， 50.0 ℃ 、344.74 kPa 条件下， 反应 114.0h， 生成 S-(+)-alloecgonine (4-nitrophenyl)ethyl ester
  参考文献：
  名称：

  Structure−Activity Relationship Comparison of (S)-2β-Substituted 3α-(Bis[4-fluorophenyl]methoxy)tropanes and (R)-2β-Substituted 3β-(3,4-Dichlorophenyl)tropanes at the Dopamine Transporter

  摘要：

  Extensive structure-activity relationships at the dopamine transporter (DAT) have been developed around two classes of tropane-based ligands. Opposing stereoselectivity and divergent structural requirements for optimal DAT binding suggest that these tropane-based DAT inhibitors may not access identical binding domains. To further investigate this hypothesis, a series of (S)-2beta-carboalkoxy-3alpha-(bis[4-fluorophenyl]methoxy)tropanes (11a-f, 13-16) and their identically (R)-2beta-substituted 3beta-(3,4-dichlorophenyl)tropanes (3, 5a-d) were prepared and evaluated for binding at the DAT and for inhibition of [H-3]dopamine uptake in rat brain. These studies showed that most of the identically 2-carboalkoxy-substituted analogues, within the two classes of compounds, bind with high affinity to DAT (K-i = 5.5 - 100 nM), albeit with opposite stereochemistry. However, the larger azido- (15) and isothiocyanato- (16) (S)-2beta-carbophenylethoxy-3alpha-(bis [4-fluorophenyl] methoxy)tropanes demonstrated a significant decrease in DAT binding potency (IC50 = 210 and 537 nM, respectively), suggesting that the DAT does not tolerate 2-position steric bulk in the benztropine class, as it does with the 2-substituted 3-aryltropanes. In addition, binding affinities at the serotonin transporter, norepinephrine transporter, and muscarinic receptors were evaluated and compared for compounds 2, 3, 11a-e, and 13. Together, the binding profiles across these systems demonstrated significant differences between these two classes of tropane-based ligands, which may be exploited toward the discovery of a cocaine-abuse pharmacotherapeutic.

  DOI：

  10.1021/jm0300375