4-[(4aR,9bR)-8-Fluoro-5-(4-fluoro-phenyl)-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indol-2-yl]-butyric acid ethyl ester | 98634-64-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-[(4aR,9bR)-8-Fluoro-5-(4-fluoro-phenyl)-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indol-2-yl]-butyric acid ethyl ester
• CAS: 98634-64-1
• 化学式: C₂₃H₂₆F₂N₂O₂
• 分子量: 400.468
• InChiKey: DIVCFRLCXFVMOV-RBBKRZOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.62
• 重原子数：
  29.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.78
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-[(4aR,9bR)-8-Fluoro-5-(4-fluoro-phenyl)-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indol-2-yl]-butyric acid ethyl ester 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 2.0h， 生成 trans-(+/-)-8-fluoro-5-(4-fluorophenyl)-2-(4-hydroxybutyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3b>indole
  参考文献：
  名称：

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

  摘要：

  Compounds derived from 4a,9b-trans-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4, 3-b]indole are consistently efficacious in displacing [3H]spiroperidol from striatal dopamine receptors in vitro. Derivatives bearing substituents at position 2, particularly those derived from butyrophenone moieties, are exceptionally potent in vivo. Compounds from the corresponding 4a,9b-cis series are substantially less potent in both in vivo and in vitro assays of neuroleptic activity. Although the cis and trans derivatives have, in some conformations, similar basic nitrogen atom to aromatic ring separations of about 5.1 A, the distance at which the basic nitrogen atom lies above or below the plane of the aromatic ring differs substantially between the two series. Consideration of these results in terms of this and earlier work indicates that the out-of-plane distance for the basic nitrogen in neuroleptic molecules may range from about 0 to about 0.90 A but may be optimized at about 0.55 A.

  DOI：

  10.1021/jm00160a050
• 作为产物：
  描述：

  4-氯丁酸乙酯 、 (-)-4a,9b-trans-8-fluoro-5-(4-fluorophenyl)-1,2,3,4,4a,9b-hexahydro-γ-carboline 在 sodium carbonate 、 potassium iodide 作用下， 以 various solvent(s) 为溶剂， 以75%的产率得到4-[(4aR,9bR)-8-Fluoro-5-(4-fluoro-phenyl)-1,3,4,4a,5,9b-hexahydro-pyrido[4,3-b]indol-2-yl]-butyric acid ethyl ester
  参考文献：
  名称：

  Neuroleptic activity of chiral trans-hexahydro-.gamma.-carbolines

  摘要：

  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.

  DOI：

  10.1021/jm00151a002