3-formyl-1-(4-toluenesulfonyl)-1H-indole-4-carbonitrile | 863407-39-0

• 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: 3-formyl-1-(4-toluenesulfonyl)-1H-indole-4-carbonitrile
• 英文别名: 3-Formyl-1-(4-methylphenyl)sulfonylindole-4-carbonitrile
• CAS: 863407-39-0
• 化学式: C₁₇H₁₂N₂O₃S
• 分子量: 324.36
• InChiKey: JBBFUXUKFKWQIW-UHFFFAOYSA-N

物化性质

• 沸点：
  581.4±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  88.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-formyl-1-(4-toluenesulfonyl)-1H-indole-4-carbonitrile 在 lithium aluminium tetrahydride 、 palladium diacetate 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 生成 trans-2-[4-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]cyclopropanecarboxaldehyde
  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：

  4-氰基吲哚-3-甲醛 、 对甲苯磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以86%的产率得到3-formyl-1-(4-toluenesulfonyl)-1H-indole-4-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

文献信息

• Conformationally Restricted Homotryptamines. 2. Indole Cyclopropylmethylamines as Selective Serotonin Reuptake Inhibitors
  作者：Ronald J. Mattson、John D. Catt、Derek J. Denhart、Jeffrey A. Deskus、Jonathan L. Ditta、Mendi A. Higgins、Lawrence R. Marcin、Charles P. Sloan、Brett R. Beno、Qi Gao、Melissa A. Cunningham、Gail K. Mattson、Thaddeus F. Molski、Matthew T. Taber、Nicholas J. Lodge

  DOI：10.1021/jm0503291

  日期：2005.9.1

  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.