trans-(+/-)-2-(3-cyanopropyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole | 77378-64-4

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: trans-(+/-)-2-(3-cyanopropyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole
• 英文别名: trans-(+/-)-2-(3-cyanopropyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole；4-[(4aR,9bR)-8-fluoro-5-(4-fluorophenyl)-3,4,4a,9b-tetrahydro-1H-pyrido[4,3-b]indol-2-yl]butanenitrile
• CAS: 77378-64-4
• 化学式: C₂₁H₂₁F₂N₃
• 分子量: 353.415
• InChiKey: CQNULHFWVJVQOD-PZJWPPBQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  30.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  trans-(+/-)-2-(3-cyanopropyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 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：

  4-氯丁腈 、 (-)-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72%的产率得到trans-(+/-)-2-(3-cyanopropyl)-8-fluoro-5-(4-fluorophenyl)-2,3,4,4a,5,9b-hexahydro-1H-pyrido<4,3-b>indole
  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

文献信息

• Hexahydro-trans- and tetrahydropyridoindole neuroleptic agents
  申请人：PFIZER INC.

  公开号：EP0060610A1

  公开（公告）日：1982-09-22

  Derivatives of 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and of (+)enantiomeric, mixtures of (+) and (-)-enantiomeric or (±)racemic 2,3,4,4a,5,9b-hexahydro-4a, 9b-trans-1H-pyrido[4,3-b]indole, substituted at the 5-position with an aryl group and at the 2-position with a carbonylaminoalkyl group or an aminoalkyl group, are neuroleptic agents useful in the treatment of certain psychoses and neuroses.

  2,3,4,5-四氢-1H-吡啶并[4,3-b]吲哚和(+)对映体的衍生物、(+)和(-)对映体的混合物或(±)外消旋2,3,4,4a,5,9b-六氢-4a,9b-反式-1H-吡啶并[4,3-b]吲哚的衍生物，在5位被芳基取代，在2位被羰基氨基烷基或氨基烷基取代，是治疗某些精神病和神经官能症的神经抑制剂。
• US4337250A
  申请人：——

  公开号：US4337250A

  公开（公告）日：1982-06-29
• US4427679A
  申请人：——

  公开号：US4427679A

  公开（公告）日：1984-01-24
• US4431646A
  申请人：——

  公开号：US4431646A

  公开（公告）日：1984-02-14
• US4431649A
  申请人：——

  公开号：US4431649A

  公开（公告）日：1984-02-14