11-(4-phenylbutyl)-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole | 147213-88-5

• 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: 11-(4-phenylbutyl)-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole
• 英文别名: 15-(4-Phenylbutyl)-9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraene
• CAS: 147213-88-5
• 化学式: C₂₃H₂₆N₂
• 分子量: 330.473
• InChiKey: YJWKPDMZHMZMRC-UHFFFAOYSA-N

物化性质

• 沸点：
  521.0±38.0 °C(predicted)
• 密度：
  1.149±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  11-(4-phenylbutyl)-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole 、 2-溴丙烷 在 sodium hydride 作用下， 生成 11-(4-phenylbutyl)-5,6,7,8,9,10-hexahydro-5-isopropyl-7,10-iminocycloheptindole
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site

  摘要：

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [H-3]-N,N'-di-o-tolylguanidine ([H-3]DTG) and [H-3]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([H-3]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [H-3]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [H-3]DTG than [H-3]-(+)-PPP-labeled sigma sites, suggesting that [H-3]DTG and [H-3]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [H-3]DTG-labeled a site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9, 10-hexahydro-7,10-iminocyclohept[b]indole(40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [H-3]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [H-3]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [H-3]DTG- and [H-3]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.

  DOI：

  10.1021/jm00055a005
• 作为产物：
  描述：

  去甲托品酮盐酸盐 在 盐酸 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 11-(4-phenylbutyl)-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site

  摘要：

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [H-3]-N,N'-di-o-tolylguanidine ([H-3]DTG) and [H-3]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([H-3]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [H-3]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [H-3]DTG than [H-3]-(+)-PPP-labeled sigma sites, suggesting that [H-3]DTG and [H-3]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [H-3]DTG-labeled a site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9, 10-hexahydro-7,10-iminocyclohept[b]indole(40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [H-3]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [H-3]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [H-3]DTG- and [H-3]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.

  DOI：

  10.1021/jm00055a005

文献信息

• Bridged .gamma.-carbolines and derivatives possessing selective and combined affinity for 5-HT2 and D2 receptors
  作者：Richard E. Mewshaw、Lisa S. Silverman、Rose M. Mathew、Carl Kaiser、Ronald G. Sherrill、Menyan Cheng、Carol W. Tiffany、E. William Karbon、Michael A. Bailey

  DOI：10.1021/jm00062a023

  日期：1993.5

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles and 6,7,8,9,10,11-hexahydro-7,-11-imino-5H-cyclooct[b]indoles was prepared. Structural modifications of the lead compound, 11-[4-(4-fluorobenzoyl)propyl]-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole (5, K(i) = 0.82 nM vs [H-3]ketanserin) enabled the identification of the functionality necessary for high affinity at serotonin 5-HT2 and dopamine D2 receptors in ligand binding studies. The indole ring, as well as the benzoyl or isosteric benzisoxazole moiety, were essential for high affinity. Variations of the length of the side chains resulted in ligands having either selective affinity for the 5-HT2 receptor or a combination of 5-HT2 and D2 affinity. In vivo binding studies were performed on selected members in this series. The most potent member, 2-fluoro-11-[4-(4-fluorobenzoyl)butyl]-5,6,7,8,9,-10-hexahydro-7,10-iminocyclohept[b]indole (36) had an ED50 of <1 mg/kg at the 5-HT2 and D2 receptors following oral administration.
• US5250537A
  申请人：——

  公开号：US5250537A

  公开（公告）日：1993-10-05
• Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site
  作者：Richard E. Mewshaw、Ronald G. Sherrill、Rose M. Mathew、Carl Kaiser、Michael A. Bailey、E. William Karbon

  DOI：10.1021/jm00055a005

  日期：1993.2

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [H-3]-N,N'-di-o-tolylguanidine ([H-3]DTG) and [H-3]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([H-3]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [H-3]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [H-3]DTG than [H-3]-(+)-PPP-labeled sigma sites, suggesting that [H-3]DTG and [H-3]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [H-3]DTG-labeled a site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9, 10-hexahydro-7,10-iminocyclohept[b]indole(40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [H-3]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [H-3]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [H-3]DTG- and [H-3]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.