3-((1S,2S)-2-hydroxymethylcyclopropyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile | 468717-34-2

• 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-((1S,2S)-2-hydroxymethylcyclopropyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile
• 英文别名: (1S,2S)-trans-2-[5-cyano-1-(4-toluenesulfonyl)-1H-indol-3-yl]cyclopropanemethanol；(-)-3-((1S,2S)-2-(hydroxymethyl)cyclopropyl)-1-tosyl-1H-indole-5-carbonitrile；(1S,2S)-trans-2-[5-cyano-1-(p-toluenesulfonyl)indol-3-yl]-cyclopropanemethanol；1H-Indole-5-carbonitrile, 3-[(1S,2S)-2-(hydroxymethyl)cyclopropyl]-1-[(4-methylphenyl)sulfonyl]-；3-[(1S,2S)-2-(hydroxymethyl)cyclopropyl]-1-(4-methylphenyl)sulfonylindole-5-carbonitrile
• CAS: 468717-34-2
• 化学式: C₂₀H₁₈N₂O₃S
• 分子量: 366.441
• InChiKey: ZPVWIZIPKCLNRA-WBVHZDCISA-N

物化性质

• 熔点：
  143.5-144.5 °C
• 沸点：
  623.3±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  91.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-((1S,2S)-2-hydroxymethylcyclopropyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile 在 sodium hydroxide 、 草酰氯 、 potassium tert-butylate 、 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 、 乙醇 、 二氯甲烷 为溶剂， 反应 5.75h， 生成 3-((1S,2S)-2-Dimethylaminomethyl-cyclopropyl)-1-methyl-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 (R)-trans-Cl₂Ru(pybox-ip)(CH₂=CH₂) 正丁基锂 、 二异丁基氢化铝 作用下， 以 四氢呋喃 、 正己烷 、 甲苯 为溶剂， 反应 20.0h， 生成 3-((1S,2S)-2-hydroxymethylcyclopropyl)-1-(toluene-4-sulfonyl)-1H-indole-5-carbonitrile
  参考文献：
  名称：

  Catalytic Asymmetric Diazoacetate Cyclopropanation of 1-Tosyl-3-vinylindoles. A Route to Conformationally Restricted Homotryptamines

  摘要：

  Substituted 1-tosyl-3-vinylindoles undergo catalytic asymmetric cyclopropanation with ethyl- and tert-butyldiazoacetate to afford N-protected trans-2-(indol-3-yl)-1-cyclopropanecarboxylic esters in good yield and high enantiomeric excess (81-88% ee). The resulting cycloadducts are demonstrated to be useful intermediates for the synthesis of conformationally restricted, homotryptamine-like analogues such as BMS-505130.

  DOI：

  10.1021/ol050790n

文献信息

• Cyclopropylindole derivatives as selective serotonin reuptake inhibitors
  申请人：——

  公开号：US20030073849A1

  公开（公告）日：2003-04-17

  The present invention relates to compounds of Formula (I) and pharmaceutically acceptable salts or solvates thereof and pharmaceutically acceptable formulations comprising said compounds 1 useful for the treatment of depression, anxiety disorders, premature ejaculation, chronic pain, obsessive-compulsive disorder, feeding disorders, premenstrual dysphoric disorder, panic disorders and psychotic disorders including bipolar disorder and schizophrenia.

  本发明涉及式(I)的化合物及其药学上可接受的盐或溶剂和包含该化合物的药学上可接受的配方，用于治疗抑郁症、焦虑障碍、早泄、慢性疼痛、强迫症、进食障碍、经前期失调障碍、恐慌障碍以及包括双相情感障碍和精神分裂症在内的精神障碍。
• Catalytic Asymmetric Diazoacetate Cyclopropanation of 1-Tosyl-3-vinylindoles. A Route to Conformationally Restricted Homotryptamines
  作者：Lawrence R. Marcin、Derek J. Denhart、Ronald J. Mattson

  DOI：10.1021/ol050790n

  日期：2005.6.1

  Substituted 1-tosyl-3-vinylindoles undergo catalytic asymmetric cyclopropanation with ethyl- and tert-butyldiazoacetate to afford N-protected trans-2-(indol-3-yl)-1-cyclopropanecarboxylic esters in good yield and high enantiomeric excess (81-88% ee). The resulting cycloadducts are demonstrated to be useful intermediates for the synthesis of conformationally restricted, homotryptamine-like analogues such as BMS-505130.
• Kilogram Synthesis of a Selective Serotonin Reuptake Inhibitor
  作者：Robert Anthes、Osagie Bello、Serge Benoit、Chien-Kuang Chen、Elisabeth Corbett、Richard M Corbett、Albert J. DelMonte、Stephane Gingras、Robert Livingston、Justin Sausker、Maxime Soumeillant

  DOI：10.1021/op700125z

  日期：2008.3.1

  Process development of a selective serotonin reuptake inhibitor (1) is described. The synthesis features Nishiyama catalyst-mediated asymmetric cyclopropanation of vinyl indole 2 with ethyldiazoacetate to install the trans-disubstituted cyclopropane. The active pharmaceutical ingredient (1) was prepared in 13 chemical steps with 9 isolations and proceeded in an overall yield of 34%.
• US6777437B2
  申请人：——

  公开号：US6777437B2

  公开（公告）日：2004-08-17
• US6822100B2
  申请人：——

  公开号：US6822100B2

  公开（公告）日：2004-11-23