N-[(1S,2S)-trans-2-[5-cyano-1-(4-toluenesulfonyl)indol-3-yl]cycloprop-1-yl]carbonylbornane-10,2-sultam | 468717-86-4

• 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-[(1S,2S)-trans-2-[5-cyano-1-(4-toluenesulfonyl)indol-3-yl]cycloprop-1-yl]carbonylbornane-10,2-sultam
• 英文别名: 3-[(1S,2S)-2-[(1R,5S,7S)-10,10-dimethyl-3,3-dioxo-3lambda6-thia-4-azatricyclo[5.2.1.01,5]decane-4-carbonyl]cyclopropyl]-1-(4-methylphenyl)sulfonylindole-5-carbonitrile；3-[(1S,2S)-2-[(1R,5S,7S)-10,10-dimethyl-3,3-dioxo-3λ6-thia-4-azatricyclo[5.2.1.01,5]decane-4-carbonyl]cyclopropyl]-1-(4-methylphenyl)sulfonylindole-5-carbonitrile
• CAS: 468717-86-4
• 化学式: C₃₀H₃₁N₃O₅S₂
• 分子量: 577.725
• InChiKey: DAASPSKOCCKNKW-AMIPKKEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.47
• 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-[(1S,2S)-trans-2-[5-cyano-1-(4-toluenesulfonyl)indol-3-yl]cycloprop-1-yl]carbonylbornane-10,2-sultam 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以81%的产率得到3-((1S,2S)-2-hydroxymethylcyclopropyl)-1-(toluene-4-sulfonyl)-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：

  3-formyl-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile 在 palladium diacetate 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 反应 25.33h， 生成 N-[(1S,2S)-trans-2-[5-cyano-1-(4-toluenesulfonyl)indol-3-yl]cycloprop-1-yl]carbonylbornane-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