[4aS,9bR]-ethyl 5-(2-amino-2-oxoethyl)-6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate | 1059630-09-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [4aS,9bR]-ethyl 5-(2-amino-2-oxoethyl)-6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate
• 英文别名: ethyl (4aS,9bR)-5-(2-amino-2-oxoethyl)-6-bromo-1,3,4,4a,5,9b-hexahydro-2H-pyrido[4,3-b]indole-2-carboxylate；ethyl (4aS,9bR)-5-(2-amino-2-oxoethyl)-6-bromo-3,4,4a,9b-tetrahydro-1H-pyrido[4,3-b]indole-2-carboxylate
• CAS: 1059630-09-9
• 化学式: C₁₆H₂₀BrN₃O₃
• 分子量: 382.257
• InChiKey: DLNYPVDXZQDBCU-AAEUAGOBSA-N

物化性质

• 沸点：
  525.6±50.0 °C(Predicted)
• 密度：
  1.462±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [4aS,9bR]-ethyl 5-(2-amino-2-oxoethyl)-6-bromo-3,4,4a,5-tetrahydro-1H-pyrido[4,3-b]indole-2(9bH)-carboxylate 在 copper(l) iodide 、 potassium carbonate 、 N,N'-二甲基乙二胺 作用下， 以 1,4-二氧六环 、 丙酮 为溶剂， 生成 (6bR,10aS)-3-methyl-2-oxo-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8-carboxylic acid ethyl ester
  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 、 (S)-(+)-扁桃酸 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium iodide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 生成 [4aS,9bR]-ethyl 5-(2-amino-2-oxoethyl)-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

文献信息

• [EN] SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES SYNTHESIS<br/>[FR] SYNTHÈSE DE GAMMA-CARBOLINES FUSIONNÉES À HÉTÉROCYCLES SUBSTITUÉS
  申请人：INTRA CELLULAR THERAPIES INC

  公开号：WO2019241278A1

  公开（公告）日：2019-12-19

  The present invention provides improved 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.

  本发明提供了改进的方法，用于制备取代杂环融合γ-咔啉，这些中间体在生产中很有用，并提供了制备这些中间体和这些杂环融合γ-咔啉的方法。
• 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 gamma-carbolines synthesis
  申请人：Intra-Cellular Therapies, Inc.

  公开号：US08309722B2

  公开（公告）日：2012-11-13

  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这些杂环融合γ-咔啉类化合物的方法。
• Substituted 2,3,4,4A,5,9B-hexahydro-1H-pyrido[4,3-B]indole derivatives synthesis and uses thereof
  申请人：Tomesch John Charles

  公开号：US08779139B2

  公开（公告）日：2014-07-15

  The present invention provides methods for the preparation of substituted 2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b]indole derivative useful as intermediates and methods for producing and using such intermediates.

  本发明提供了制备取代的2,3,4,4a,5,9b-六氢-1H-吡啶[4,3-b]吲哚衍生物的方法，该衍生物作为中间体有用，并提供了制备和使用这种中间体的方法。
• 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。