3,9-二甲氧基-5,8,13,13alpha-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇 | 16562-14-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 中文名称: 3,9-二甲氧基-5,8,13,13alpha-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇
• 中文别名: ,9-二甲氧基-5,8,13,13α-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇；9-二甲氧基-5,8,13,13α-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇
• 英文名称: 2,10-dihydroxy-3,9-dimethoxy-5,8,13,13a-tetrahydro-6H-dibenzo[a,g]quinolizine
• 英文别名: (+/-)-stepholidine；D,L-stepholidine；stepholidine；3,9-dimethoxy-5,8,13,13a-tetrahydro-6H-isoquino[3,2-a]isoquinoline-2,10-diol；(+/-)-Stepholidin；Stephdidin；3,9-dimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline-2,10-diol
• CAS: 16562-14-4
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: JKPISQIIWUONPB-UHFFFAOYSA-N

物化性质

• 熔点：
  120-1220C
• 沸点：
  524.0±50.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（轻微，超声处理），甲醇（轻微）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  62.2
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  4-bromo-1-(ethoxymethoxy)-2-methoxybenzene 在 盐酸 、 lithium aluminium tetrahydride 、 正丁基锂 、 水 、 potassium carbonate 、 二异丙胺 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 生成 3,9-二甲氧基-5,8,13,13alpha-四氢-6H-异喹啉并[3,2-a]异喹啉-2,10-二醇
  参考文献：
  名称：

  Tetrahydroprotoberberine alkaloids with dopamine and σ receptor affinity

  摘要：

  Two series of analogues of the tetrahydroprotoberberine (THPB) alkaloid (+/-)-stepholidine that (a) contain various alkoxy substituents at the C10 position and, (b) were de-rigidified with respect to (+/-)-stepholidine, were synthesized and evaluated for affinity at dopamine and sigma receptors in order to evaluate effects on D3 and sigma 2 receptor affinity and selectivity. Small n-alkoxy groups are best tolerated by D3 and sigma 2 receptors. Among all compounds tested, C10 methoxy and ethoxy analogues (10 and 11 respectively) displayed the highest affinity for sigma 2 receptors as well as sigma 2 versus sigma 1 selectivity and also showed the highest D3 receptor affinity. De-rigidification of stepholidine resulted in decreased affinity at all receptors evaluated; thus the tetracyclic THPB framework is advantageous for affinity at dopamine and sigma receptors. Docking of the C10 analogues at the D3 receptor, suggest that an ionic interaction between the protonated nitrogen atom and Asp110, a H-bond interaction between the C2 phenol and Ser192, a H-bond interaction between the C10 phenol and Cys181 as well as hydrophobic interactions of the aryl rings to Phe106 and Phe345, are critical for high affinity of the compounds. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2016.03.037

文献信息

• [EN] DOPAMINE D2 RECEPTOR LIGANDS<br/>[FR] LIGANDS DES RÉCEPTEURS DOPAMINERGIQUES D2
  申请人：BROAD INST INC

  公开号：WO2016100940A1

  公开（公告）日：2016-06-23

  The present invention relates to novel dopamine D2 receptor ligands. The invention further relates to functionally-biased dopamine D2 receptor ligands and the use of these compounds for treating or preventing central nervous system and systemic disorders associated with dysregulation of dopaminergic activity. The present invention relates to novel compounds that modulate dopamine D2 receptors. In particular, compounds of the present invention show functional selectivity at the dopamine D2 receptors and exhibit selectivity downstream of the D2 receptors, on the 0- arrestin pathway and/or on the cAMP pathway.

  本发明涉及新型多巴胺D2受体配体。该发明进一步涉及功能偏向的多巴胺D2受体配体以及利用这些化合物治疗或预防与多巴胺活性失调相关的中枢神经系统和全身性疾病。本发明涉及调节多巴胺D2受体的新型化合物。具体而言，本发明的化合物在多巴胺D2受体上显示功能选择性，并在D2受体下游、0-阿雷斯汀途径和/或cAMP途径上表现出选择性。
• [EN] TETRAHYDROPROTOBERBINE COMPOUNDS AND USES THEREOF IN THE TREATMENT OF NEUROLOGICAL, PSYCHIATRIC AND NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS TÉTRAHYDROPROTOBERBINES ET LEURS UTILISATIONS DANS LE TRAITEMENT DE MALADIES NEUROLOGIQUES, PSYCHIATRIQUES ET NEURODÉGÉNÉRATIVES
  申请人：MILLER JAMES JACKSON

  公开号：WO2013020229A1

  公开（公告）日：2013-02-14

  Tetrahydroprotoberbine (THPB) compounds and their use in the treatment of neurological, psychiatric and neurodegenerative diseases is provided. The compounds include d-govadine, l-govadine and racemic govadine, as well as d-THPBs of general formula (I). Enantioselective processes for preparing compounds of formula (I), and d- and l-govadine are also provided.(I)

  提供了Tetrahydroprotoberbine (THPB)化合物及其在治疗神经系统、精神疾病和神经退行性疾病中的用途。这些化合物包括d-govadine、l-govadine和racemic govadine，以及通式(I)的d-THPBs。还提供了制备通式(I)化合物和d-、l-govadine的对映选择性过程。(I)
• 光学异构的千金藤啶碱及其衍生物的制备方法
  申请人：山东特珐曼药业有限公司

  公开号：CN102399166B

  公开（公告）日：2016-04-27

  本发明涉及一种通式(I)所示的化合物，其中各取代基的定义如说明书中所述。本发明还涉及该化合物的制备方法，该化合物在制备光学异构的四氢原小檗碱类化合物中的应用，以及其在制备光学异构的四氢原小檗碱类化合物的中间体。
• [EN] BERBERINE COMPOUNDS, BERBERINE COMPOSITIONS, AND METHODS FOR ADMINISTRATION THEREOF<br/>[FR] COMPOSÉS DE BERBÉRINE, COMPOSITIONS DE BERBÉRINE ET LEURS PROCÉDÉS D'ADMINISTRATION
  申请人：DIGNITY HEALTH

  公开号：WO2021162750A1

  公开（公告）日：2021-08-19

  Compounds and berberine compositions containing such compounds that are useful for reducing nicotine dependency. Methods for administering the berberine compositions are also disclosed. The compounds may have a structure according to Formula (I). In Formula (I) R1, R2, R3, R4, and R5 are independently H or D; R6 and R7 are independently hydrogen, deuterium, halogen, C4 to C8 unsubstituted aryl, C4 to C8 substituted aryl, C2 to C6 unsubstituted heterocycle, C2 to C6 substituted heterocycle, C1 to C6 unsubstituted alkyl, C1 to C6 substituted alkyl, C3-C10 unsubstituted cycloalkyl, C3- C10 substituted cycloalkyl, or R6 and R7 are taken together as =O or =S; and R8 and R9 are independently selected from a group consisting of methyl, CHF2, and CF3.

  化合物和含有这些化合物的黄连素组合物可用于减少尼古丁依赖性。还公开了给予黄连素组合物的方法。这些化合物的结构可能符合公式（I）。在公式（I）中，R1，R2，R3，R4和R5独立地为H或D；R6和R7独立地为氢，氘，卤素，未取代的C4到C8芳基，取代的C4到C8芳基，未取代的C2到C6杂环，取代的C2到C6杂环，未取代的C1到C6烷基，取代的C1到C6烷基，未取代的C3-C10环烷基，取代的C3-C10环烷基，或者R6和R7一起作为=O或=S；R8和R9独立地选自甲基，CHF2和CF3组成的一组。
• [EN] PREPARATION METHODS OF OPTICAL ISOMERS OF STEPHOLIDINE OR ITS DERIVATIVES AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉS DE PRÉPARATION D'ISOMÈRES OPTIQUES DE LA STÉPHOLIDINE OU DE SES DÉRIVÉS OU INTERMÉDIAIRES DE CELLE-CI
  申请人：SHANGHAI INST MATERIA MEDICA

  公开号：WO2010145206A1

  公开（公告）日：2010-12-23

  Preparation methods of optical isomers of stepholidine or its derivatives and intermediates thereof are disclosed. Especially, Preparation methods of L-stepholidine or optical isomers of its derivatives are disclosed. Said optical isomers of stepholidine or its derivatives are prepared by catalytic asymmetric hydrogenation from 3,4-dihydroisoquinoline of formula I in the participation of the chiral metal catalyst.

  本发明揭示了史保利定及其衍生物的光学异构体的制备方法和中间体。特别地，揭示了L-史保利定或其衍生物的光学异构体的制备方法。所述的史保利定或其衍生物的光学异构体是通过在手性金属催化剂的参与下，从式I的3,4-二氢异喹啉进行催化不对称氢化制备的。