(10S^*,11S^*)-11-(tert-butylcarboxamido)-10,11-dihydro-10-hydroxy-5-methyl-5H-dibenzocycloheptene | 125025-42-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (10S^*,11S^*)-11-(tert-butylcarboxamido)-10,11-dihydro-10-hydroxy-5-methyl-5H-dibenzocycloheptene
• 英文别名: (10S^*,11S^*)-11-(tert-butylcarboxamido)-10,11-dihydro-10-hydroxy-5-methyl-5H-dibenzo[a,d]cycloheptene
• CAS: 125025-42-5；125134-16-9
• 化学式: C₂₁H₂₅NO₄
• 分子量: 355.434
• InChiKey: VPDWYUCXTXZKAW-GAOSQQNJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  26.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  78.79
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (10S^*,11S^*)-11-(tert-butylcarboxamido)-10,11-dihydro-10-hydroxy-5-methyl-5H-dibenzocycloheptene 在 对甲苯磺酸 、 三氟乙酸 作用下， 以 氯仿 、 苯 为溶剂， 反应 2.0h， 生成 (5R^*,10S^*,11S^*)-10,11-dihydro-11-hydroxy-5-methyl-5H-dibenzocyclohepten-5,10-imine
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists

  摘要：

  A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.

  DOI：

  10.1021/jm00164a052
• 作为产物：
  描述：

  N-chloro-N-sodio-tert-butylcarbamate 在 四氧化锇 、 silver nitrate 作用下， 以 四氢呋喃 为溶剂， 反应 16.37h， 生成 (10S^*,11S^*)-11-(tert-butylcarboxamido)-10,11-dihydro-10-hydroxy-5-methyl-5H-dibenzocycloheptene
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of a series of dibenzo[a,d]cycloalkenimines as N-methyl-D-aspartate antagonists

  摘要：

  A series of 73 dibenzo[a,d]cycloalkenimines were synthesized and evaluated for their ability to displace (+)-10,11-dihydro-5-methyl-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]-(+)-10) from its specific binding site on rat cortical membranes. A number of the more active compounds (Ki ranging from 0.006 to 0.21 microM) were evaluated for N-methyl-D-aspartate (NMDA) antagonist activity in the rat cortical slice (Kb ranging from 0.08 to 0.9 microM) and anticonvulsant activity in the mouse against NMDA induced convulsions. The ED50 values ranged from 0.22 to 7.76 mg/kg and correlated reasonably well with the Kb determination. In the dibenzo[a,d]cyclohepten-5,10-imine series, the (+)-5S,10R enantiomer displayed consistently higher levels of biological activity. While substitution at the 3-position of (+)-10 with electronegative atoms generally increased in vitro activity, a loss of potency relative to (+)-10 (MK-801) was observed in vivo for all of the compounds tested.

  DOI：

  10.1021/jm00164a052