trans-(+/-)-2-(4-aminobutyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole | 98651-79-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-(+/-)-2-(4-aminobutyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole
• 英文别名: 4-[(4aR,9bR)-8-fluoro-5-(4-fluorophenyl)-3,4,4a,9b-tetrahydro-1H-pyrido[4,3-b]indol-2-yl]butan-1-amine
• CAS: 98651-79-7
• 化学式: C₂₁H₂₅F₂N₃
• 分子量: 357.446
• InChiKey: BSTZARUSCKCGSQ-PZJWPPBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-(+/-)-2-(4-aminobutyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole 、 乙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 trans-(+/-)-2-(4-acetamidobutyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole
  参考文献：
  名称：

  Neuroleptics from the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 3. Carboxamidoalkyl derivatives

  摘要：

  Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the analogous 4-hydroxy-4-(4-fluorophenyl)butyl derivatives reported previously, the absolute potency in vivo is greater. The ability of these compounds to bind with great affinity to dopamine (DA) receptors further defines the nature of the DA receptor auxiliary binding site as a hydrogen-bond donating site in addition to or instead of a lipophilic site as has been previously proposed.

  DOI：

  10.1021/jm00160a053
• 作为产物：
  描述：

  (-)-4a,9b-trans-8-fluoro-5-(4-fluorophenyl)-1,2,3,4,4a,9b-hexahydro-γ-carboline 在 lithium aluminium tetrahydride 、 sodium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 反应 1.0h， 生成 trans-(+/-)-2-(4-aminobutyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole
  参考文献：
  名称：

  Neuroleptics from the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 3. Carboxamidoalkyl derivatives

  摘要：

  Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the analogous 4-hydroxy-4-(4-fluorophenyl)butyl derivatives reported previously, the absolute potency in vivo is greater. The ability of these compounds to bind with great affinity to dopamine (DA) receptors further defines the nature of the DA receptor auxiliary binding site as a hydrogen-bond donating site in addition to or instead of a lipophilic site as has been previously proposed.

  DOI：

  10.1021/jm00160a053

文献信息

• Neuroleptic activity of chiral trans-hexahydro-.gamma.-carbolines
  作者：Reinhard Sarges、Harry R. Howard、Kathy M. Donahue、Williard M. Welch、Beryl W. Dominy、Albert Weissman、B. Kenneth Koe、Jon Bordner

  DOI：10.1021/jm00151a002

  日期：1986.1

  A series of trans-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5, 9b-hexahydro-1H-pyrido[4,3-b]indoles with various N-2 substituents has been prepared and tested for neuroleptic activity [( 3H]spiroperidol binding and amphetamine antagonism). Several members of this series showed exceptional in vivo potency, especially the hydantoin derivatives 27-30. Resolution into the enantiomers showed that neuroleptic activity is associated with the 4aS,9bS absolute configuration. These rigid neuroleptics have been correlated with other rigid neuroleptics [(+)-dexclamol, Ro 22-1319] and can serve to further define the topography of the dopamine receptor.
• Neuroleptics from the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole series. 3. Carboxamidoalkyl derivatives
  作者：Willard M. Welch、Charles A. Harbert、Reinhard Sarges、Albert Weissman、B. Kenneth Koe

  DOI：10.1021/jm00160a053

  日期：1986.10

  Substitution of position 2 of the 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole nucleus with omega-carboxamidoalkyl substituents leads to compounds with exceedingly potent neuroleptic activity in in vitro and in vivo models. Although duration of activity is not as long as that of the analogous 4-hydroxy-4-(4-fluorophenyl)butyl derivatives reported previously, the absolute potency in vivo is greater. The ability of these compounds to bind with great affinity to dopamine (DA) receptors further defines the nature of the DA receptor auxiliary binding site as a hydrogen-bond donating site in addition to or instead of a lipophilic site as has been previously proposed.