6-溴甲基-2,3,4,4A,5,9B-六氢-1H-吡啶并[4,3-B]吲哚 | 1059630-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 6-溴甲基-2,3,4,4A,5,9B-六氢-1H-吡啶并[4,3-B]吲哚
• 英文名称: racemate 6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole
• 英文别名: 6-bromo-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole
• CAS: 1059630-12-4
• 化学式: C₁₁H₁₃BrN₂
• 分子量: 253.142
• InChiKey: LPBJHSPFSUDRSY-UHFFFAOYSA-N

物化性质

• 沸点：
  338.4±42.0 °C(Predicted)
• 密度：
  1.416±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  24.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302
• 储存条件：
  应存放在室温、避光且充满惰性气体的环境中。

反应信息

• 作为反应物：
  描述：

  6-溴甲基-2,3,4,4A,5,9B-六氢-1H-吡啶并[4,3-B]吲哚 在 (S)-(+)-扁桃酸 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (4aS,9bR)-ethyl 6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate
  参考文献：
  名称：

  ITI-007. 5-HT2A receptor antagonist, dopamine D2 receptor modulator, treatment of schizophrenia, treatment of insomnia

  摘要：

  A great deal has been achieved in the treatment of schizophrenia in recent decades, especially the treatment of the positive symptoms by targeting dopamine D-2 receptors. But the disease has a range of other symptoms which gravely affect quality of life and which require other strategies or additional targets. Among the agents gradually filling the empty therapeutic space is ITI-007, which has an unusual mechanistic profile: it targets 5-HT2A and dopamine D-2 receptors, but has a much higher affinity for the former receptors. This may allow the drug's effects to be modified by dose adjustments, with effects on sleep disturbances, depression and anxiety seen with lower doses and higher doses affecting the positive symptoms of schizophrenia through dopamine D-2 receptor modulation. Higher doses can also inhibit serotonin transporters and produce glutamatergic modulation which could improve positive and negative symptoms, depressive symptoms and cognitive impairments. The findings of preclinical studies have supported this view of the drug, and a phase II study found effects on positive and negative symptoms with a safety profile distinct from atypical antipsychotics. Phase III investigation in schizophrenia has begun, and clinical investigation in insomnia and dementia is also under way.

  DOI：

  10.1358/dof.2015.040.10.2387229
• 作为产物：
  描述：

  2-溴苯肼盐酸盐 在 盐酸 、 三乙基硅烷 、 三氟乙酸 作用下， 以 乙醇 为溶剂， 生成 6-溴甲基-2,3,4,4A,5,9B-六氢-1H-吡啶并[4,3-B]吲哚
  参考文献：
  名称：

  ITI-007. 5-HT2A receptor antagonist, dopamine D2 receptor modulator, treatment of schizophrenia, treatment of insomnia

  摘要：

  A great deal has been achieved in the treatment of schizophrenia in recent decades, especially the treatment of the positive symptoms by targeting dopamine D-2 receptors. But the disease has a range of other symptoms which gravely affect quality of life and which require other strategies or additional targets. Among the agents gradually filling the empty therapeutic space is ITI-007, which has an unusual mechanistic profile: it targets 5-HT2A and dopamine D-2 receptors, but has a much higher affinity for the former receptors. This may allow the drug's effects to be modified by dose adjustments, with effects on sleep disturbances, depression and anxiety seen with lower doses and higher doses affecting the positive symptoms of schizophrenia through dopamine D-2 receptor modulation. Higher doses can also inhibit serotonin transporters and produce glutamatergic modulation which could improve positive and negative symptoms, depressive symptoms and cognitive impairments. The findings of preclinical studies have supported this view of the drug, and a phase II study found effects on positive and negative symptoms with a safety profile distinct from atypical antipsychotics. Phase III investigation in schizophrenia has begun, and clinical investigation in insomnia and dementia is also under way.

  DOI：

  10.1358/dof.2015.040.10.2387229

文献信息

• SUBSTITUTED HETEROCYCLE GAMMA-CARBOLINES SYNTHESIS
  申请人：Tomesch John Charles

  公开号：US20100113781A1

  公开（公告）日：2010-05-06

  The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines.

  本发明提供了制备取代杂环融合的γ-咔啉类化合物的方法，以及用于生产它们的中间体和制备这些中间体和杂环融合的γ-咔啉类化合物的方法。
• SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES SYNTHESIS
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US20140364609A1

  公开（公告）日：2014-12-11

  The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines.

  本发明提供了制备取代杂环融合γ-咔啉的方法，这些中间体在生产它们和这些杂环融合γ-咔啉的方法中是有用的。
• Preparation of certain substituted [((6bR,10aS)-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalines and pharmaceutically acceptable salts thereof
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US10221176B2

  公开（公告）日：2019-03-05

  The present invention provides methods for the preparation of substituted heterocycle fused gamma-carbolines of Formula 2F, as shown below, intermediates useful in producing them and methods for producing such intermediates and such heterocycle fused gamma-carbolines, such methods comprising the preparation of a Compound of Formula 2F, as shown below and as further defined herein:

  本发明提供了如下式 2F 所示的取代杂环融合γ-羰基化合物的制备方法、用于制备它们的中间体以及生产这种中间体和这种杂环融合γ-羰基化合物的方法，这种方法包括制备如下式所示并在此进一步定义的式 2F 化合物：
• Pharmaceutical compositions comprising ((6bR,10aS)-1-(4-fluorophenyl)-4-(3-methyl-2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl)butan-1-one or pharmaceutically acceptable salts thereof
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US10464938B2

  公开（公告）日：2019-11-05

  The present invention provides pharmaceutical compositions comprising certain optionally substituted heterocycle fused gamma-carbolines of Formula 2J, as shown below, and as further defined herein:

  本发明提供了药物组合物，其中包含如下所示的某些任选取代的杂环融合γ-咔啉，并在此进一步定义：
• Preparation of certain substituted 1-(4-fluorophenyl)-4-(2,3,6b,9,10,10a-hexahydro-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-YL)butan-1-ones and pharmaceutically acceptable salts thereof
  申请人：INTRA-CELLULAR THERAPIES, INC.

  公开号：US10597395B2

  公开（公告）日：2020-03-24

  The present invention provides methods for the preparation of certain optionally substituted heterocycle fused gamma-carbolines of Formula 2J, as shown below and as further defined herein:

  本发明提供了如下所示和本文进一步定义的某些任选取代的杂环融合γ-咔啉的式 2J 的制备方法：