(6BR,10AS)-3-甲基-2,3,6B,7,8,9,10,10A-八氢-1H-吡啶基[3',4':4,5]吡咯并[1,2,3-DE]喹喔啉 | 313368-85-3

• 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: (6BR,10AS)-3-甲基-2,3,6B,7,8,9,10,10A-八氢-1H-吡啶基[3',4':4,5]吡咯并[1,2,3-DE]喹喔啉
• 英文名称: (6bR,10aS)-3-methyl-2,3,6b,7,8,9,10,10a-octahydro-1H-pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline
• 英文别名: (10R,15S)-4-methyl-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-triene
• CAS: 313368-85-3
• 化学式: C₁₄H₁₉N₃
• 分子量: 229.325
• InChiKey: QLGUCSLWLPCOTR-RYUDHWBXSA-N

物化性质

• 沸点：
  374.5±42.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  18.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  应存放在2-8°C的环境中，避免光照，并保持在惰性气体中。

反应信息

• 作为反应物：
  描述：

  (6BR,10AS)-3-甲基-2,3,6B,7,8,9,10,10A-八氢-1H-吡啶基[3',4':4,5]吡咯并[1,2,3-DE]喹喔啉 在 盐酸 、 三乙胺 、 potassium iodide 作用下， 以 甲醇 、 乙酸乙酯 、 异丙醇 、 甲苯 为溶剂， 反应 18.0h， 生成 1-(4-氟苯基)-4-[(6BR,10AS)-2,3,6B,9,10,10A-六氢-3-甲基-1H-吡啶并[3',4':4,5]吡咯并[1,2,3-DE]喹喔啉-8(7H)-基]-1-丁酮对甲苯磺酸盐
  参考文献：
  名称：

  [EN] METHOD FOR THE MANUFACTURE OF LUMATEPERONE AND ITS SALTS
  [FR] PROCÉDÉ POUR LA FABRICATION DE LUMATÉPÉRONE ET DE SES SELS

  摘要：

  生产配方（I）卢马特贝隆或其酸盐的方法，以便通过分辨法将立体化学为6bR，10aS的对映异构体与顺式混合物分离，使用配方（II）立体异构体与4-卤代-4'-氟丁酮苯（X = I，Br，Cl）烷基化，制备配方（I）卢马特贝隆，或可选择其酸盐。本发明的目的还涉及卢马特贝隆形态上均匀的对甲苯磺酸盐和卢马特贝隆的萘-2-磺酸盐，以及与萘-2-磺酸形成的1：2化学计量比的卢马特贝隆盐。

  公开号：

  WO2019102240A1
• 作为产物：
  描述：

  2-溴苯肼盐酸盐 在 盐酸 、 三乙基硅烷 、 硼烷四氢呋喃络合物 、 (S)-(+)-扁桃酸 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium iodide 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 正丁醇 为溶剂， 生成 (6BR,10AS)-3-甲基-2,3,6B,7,8,9,10,10A-八氢-1H-吡啶基[3',4':4,5]吡咯并[1,2,3-DE]喹喔啉
  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 fused gamma-carbolines
  申请人：——

  公开号：US20040220178A1

  公开（公告）日：2004-11-04

  The present invention is directed to methods of treating addictive behavior and sleep disorders by administering compounds represented by structural Formula (I) 1 or pharmaceutically acceptable salt forms thereof, wherein R 1 , R 5 , R 6a , R 6b , R 7 , R 8 , R 9 , X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.

  本发明涉及通过给予由结构式（I）表示的化合物或其药学上可接受的盐形式来治疗成瘾行为和睡眠障碍的方法，其中R1、R5、R6a、R6b、R7、R8、R9、X、b、k、m和n以及虚线如本文所述。本发明治疗方法中使用的化合物是5-羟色胺激动剂和拮抗剂，对于控制或预防包括成瘾行为和睡眠障碍在内的中枢神经系统疾病是有用的。
• [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。
• [EN] ORGANIC COMPOUNDS<br/>[FR] COMPOSÉS ORGANIQUES
  申请人：INTRA-CELLULAR THERAPIES INC

  公开号：WO2017165843A1

  公开（公告）日：2017-09-28

  The invention relates to particular substituted deuterated heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and/or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and/or pathways involving dopamine D1/D2 receptor signaling systems, and/or the treatment of residual symptoms.

  本发明涉及特定的取代的氘代杂环融合的γ-咔啉，它们的前药，在自由的、固态的、药学上可接受的盐和/或在本文中描述的基本纯净形式中，以及其制药组合物，以及在涉及5-HT2A受体、血清素转运体（SERT）和/或涉及多巴胺D1/D2受体信号系统的途径，以及/或治疗残余症状方面的疾病治疗方法。
• [EN] ORGANIC COMPOUND<br/>[FR] COMPOSÉ ORGANIQUE
  申请人：INTRA CELLULAR THERAPIES INC

  公开号：WO2021119334A1

  公开（公告）日：2021-06-17

  The invention relates to a particular substituted heterocycle fused gamma-carboline, the compound of Formula I, and new methods and uses pertaining thereto, and pharmaceutical compositions thereof, such as methods of use in the treatment of diseases involving the 5-HT receptor, the serotonin transporter (SERT), and/or pathways involving dopamine D2 receptor signaling, sodium channel activity, and/or norepinephrine transporter activity.

  本发明涉及一种特定的取代杂环融合的γ-咔啉化合物，化合物的化学式为I，以及与此相关的新方法和用途，以及其制备的药物组合物，如用于治疗涉及5-HT受体、血清素转运体（SERT）和/或多巴胺D2受体信号通路、钠通道活性和/或去甲肾上腺素转运体活性的疾病的使用方法。
• Substituted heterocycle fused γ-carbolines
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US07183282B2

  公开（公告）日：2007-02-27

  The present invention is directed to compounds useful for treating addictive behavior and sleep disorders represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R1, R5, R6a, R6b, R7, R8, R9, X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.

  本发明涉及用于治疗成瘾行为和睡眠障碍的化合物，其结构式表示为（I）或其药学上可接受的盐形式，其中R1、R5、R6a、R6b、R7、R8、R9、X、b、k、m和n以及虚线如本文所述。本发明治疗方法中使用的化合物是5-羟色胺激动剂和拮抗剂，可用于控制或预防中枢神经系统疾病，包括成瘾行为和睡眠障碍。