trans-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-N-methoxy-N-methylacrylamide | 468717-74-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: trans-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-N-methoxy-N-methylacrylamide
• 英文别名: (E)-3-[5-cyano-1-(4-methylphenyl)sulfonylindol-3-yl]-N-methoxy-N-methylprop-2-enamide
• CAS: 468717-74-0
• 化学式: C₂₁H₁₉N₃O₄S
• 分子量: 409.466
• InChiKey: LFEKBSZABGEXPZ-YRNVUSSQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-N-methoxy-N-methylacrylamide 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 potassium tert-butylate 、 palladium diacetate 、 三乙酰氧基硼氢化钠 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 6.25h， 生成 3-((1S,2S)-2-Dimethylaminomethyl-cyclopropyl)-1-ethyl-1H-indole-5-carbonitrile
  参考文献：
  名称：

  Conformationally Restricted Homotryptamines. 2. Indole Cyclopropylmethylamines as Selective Serotonin Reuptake Inhibitors

  摘要：

  A series of indole cyclopropylmethylamines were found to be potent serotonin reuptake inhibitors. Nitrile substituents at the 5 and 7 positions of the indole ring gave high affinity for hSERT, and the preferred cyclopropane stereochemistry was determined to be (1S,2S)-trans. The cis-cyclopropanes had 20- to 30-fold less affinity than the trans, and the preferred cis stereochemistry was (1R,2S)-cis. Substitution of the indole N-1 position with methyl or ethyl groups gave a 10- to 30-fold decrease in affinity for hSERT, suggesting either a hydrogen-bonding interaction or limited steric tolerance in the region of the indole nitrogen. Compound (+)-12a demonstrated potent hSERT binding (K-i = 0.18 nM) in vitro and was more than 1000-fold less potent at hDAT, hNET, 5-HT1A, and 5-HT6. In vivo, (+)-12a produced robust, dose-dependent increases in extracellular serotonin in rat frontal cortex typical of a selective serotonin reuptake inhibitor. The maximal response produced by (+)-12a was similar to that of fluoxetine but at an approximately 10-fold lower dose.

  DOI：

  10.1021/jm0503291
• 作为产物：
  描述：

  5-氰基吲哚-3-甲醛 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 trans-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-N-methoxy-N-methylacrylamide
  参考文献：
  名称：

  Conformationally Restricted Homotryptamines. 2. Indole Cyclopropylmethylamines as Selective Serotonin Reuptake Inhibitors

  摘要：

  A series of indole cyclopropylmethylamines were found to be potent serotonin reuptake inhibitors. Nitrile substituents at the 5 and 7 positions of the indole ring gave high affinity for hSERT, and the preferred cyclopropane stereochemistry was determined to be (1S,2S)-trans. The cis-cyclopropanes had 20- to 30-fold less affinity than the trans, and the preferred cis stereochemistry was (1R,2S)-cis. Substitution of the indole N-1 position with methyl or ethyl groups gave a 10- to 30-fold decrease in affinity for hSERT, suggesting either a hydrogen-bonding interaction or limited steric tolerance in the region of the indole nitrogen. Compound (+)-12a demonstrated potent hSERT binding (K-i = 0.18 nM) in vitro and was more than 1000-fold less potent at hDAT, hNET, 5-HT1A, and 5-HT6. In vivo, (+)-12a produced robust, dose-dependent increases in extracellular serotonin in rat frontal cortex typical of a selective serotonin reuptake inhibitor. The maximal response produced by (+)-12a was similar to that of fluoxetine but at an approximately 10-fold lower dose.

  DOI：

  10.1021/jm0503291