(+)-N-[(E)-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-2-propenoyl]bornane-10,2-sultam | 468717-85-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-N-[(E)-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-2-propenoyl]bornane-10,2-sultam
• 英文别名: 3-[(E)-3-[(1R,5S,7S)-10,10-dimethyl-3,3-dioxo-3lambda6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]-3-oxoprop-1-enyl]-1-(4-methylphenyl)sulfonylindole-5-carbonitrile；3-[(E)-3-[(1R,5S,7S)-10,10-dimethyl-3,3-dioxo-3λ6-thia-4-azatricyclo[5.2.1.01,5]decan-4-yl]-3-oxoprop-1-enyl]-1-(4-methylphenyl)sulfonylindole-5-carbonitrile
• CAS: 468717-85-3
• 化学式: C₂₉H₂₉N₃O₅S₂
• 分子量: 563.698
• InChiKey: XEFHWHLRONCINA-WCMNSPLISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-N-[(E)-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-2-propenoyl]bornane-10,2-sultam 在 lithium aluminium tetrahydride 、 草酰氯 、 palladium diacetate 、 三乙酰氧基硼氢化钠 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 3.58h， 生成 (1S,2S)-trans-1-(N,N-dimethylaminomethyl)-2-[5-cyano-1-(p-toluenesulfonyl)indol-3-yl]-cyclopropane
  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 49.0h， 生成 (+)-N-[(E)-3-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]-2-propenoyl]bornane-10,2-sultam
  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