(1R,3R,5S)-3-(5-Chloro-2,2-dimethyl-2,3-dihydro-benzofuran-7-carbonyloxy)-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 2,2,2-trichloro-ethyl ester | 813420-10-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1R,3R,5S)-3-(5-Chloro-2,2-dimethyl-2,3-dihydro-benzofuran-7-carbonyloxy)-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 2,2,2-trichloro-ethyl ester
• CAS: 813420-10-9
• 化学式: C₂₁H₂₃Cl₄NO₅
• 分子量: 511.229
• InChiKey: ZOJIMBDZUBBWNZ-FICVDOATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.71
• 重原子数：
  31.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  65.07
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (1R,3R,5S)-3-(5-Chloro-2,2-dimethyl-2,3-dihydro-benzofuran-7-carbonyloxy)-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 2,2,2-trichloro-ethyl ester 在 溶剂黄146 、 锌 作用下， 反应 2.0h， 生成 3α-(2',3'-benzofuran-5',5'-dimethyl-8'-chloro-6'-carbonyloxo)nortropane
  参考文献：
  名称：

  Synthesis of Tropeines and Allosteric Modulation of Ionotropic Glycine Receptors

  摘要：

  Twenty esters of 3alpha- and 3beta-hydroxy(nor)tropanes and two amides of 3alpha-aminotropane were prepared with substituted benzoic acids. These (nor)tropeines inhibited [H-3] strychnine binding to glycine receptors in synaptosomal membranes of rat spinal cord. A ternary allosteric model was applied to determine the dissociation constants (K-A) of the tropeines having strong negative cooperativities with [H-3]strychnine binding (alpha > 10). K-A values about 10 nM are well below those of known allosteric agents. Low concentrations (0.1K(A)) of the (nor)tropeines potentiated the displacing effects of glycine. Positive cooperativity with glycine (beta < 1) decreased with the increase in concentration and binding affinity of tropeines. Displacing potencies were also measured for [H-3]granisetron binding to 5-HT3 type serotonin receptors of rat cerebral cortex. Selectivities to glycine receptors versus 5-HT3 receptors varied within 4 orders of magnitude. Nortropeines might serve as a lead to high-affinity selective allosteric modulators of glycine receptors.

  DOI：

  10.1021/jm040814g
• 作为产物：
  描述：

  5-Chloro-2,2-dimethyl-2,3-dihydro-1-benzofuran-7-carbonyl chloride 在 TEA 、 potassium carbonate 作用下， 以 甲苯 为溶剂， 反应 5.33h， 生成 (1R,3R,5S)-3-(5-Chloro-2,2-dimethyl-2,3-dihydro-benzofuran-7-carbonyloxy)-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 2,2,2-trichloro-ethyl ester
  参考文献：
  名称：

  Synthesis of Tropeines and Allosteric Modulation of Ionotropic Glycine Receptors

  摘要：

  Twenty esters of 3alpha- and 3beta-hydroxy(nor)tropanes and two amides of 3alpha-aminotropane were prepared with substituted benzoic acids. These (nor)tropeines inhibited [H-3] strychnine binding to glycine receptors in synaptosomal membranes of rat spinal cord. A ternary allosteric model was applied to determine the dissociation constants (K-A) of the tropeines having strong negative cooperativities with [H-3]strychnine binding (alpha > 10). K-A values about 10 nM are well below those of known allosteric agents. Low concentrations (0.1K(A)) of the (nor)tropeines potentiated the displacing effects of glycine. Positive cooperativity with glycine (beta < 1) decreased with the increase in concentration and binding affinity of tropeines. Displacing potencies were also measured for [H-3]granisetron binding to 5-HT3 type serotonin receptors of rat cerebral cortex. Selectivities to glycine receptors versus 5-HT3 receptors varied within 4 orders of magnitude. Nortropeines might serve as a lead to high-affinity selective allosteric modulators of glycine receptors.

  DOI：

  10.1021/jm040814g