(R)(-)-2,10,11-trihydroxyaporphine hydrobromide | 82331-73-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: (R)(-)-2,10,11-trihydroxyaporphine hydrobromide
• 英文别名: R(-)-2,10,11-trihydroxyaporphine hybrobromide；O-Demethylmorphothebaine hydrobromide；(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,10,11-triol;hydrobromide
• CAS: 82331-73-5
• 化学式: BrH*C₁₇H₁₇NO₃
• 分子量: 364.239
• InChiKey: SJXJEAQVHBGSDL-BTQNPOSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.13
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  63.9
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (R)(-)-2,10,11-trihydroxyaporphine hydrobromide 在 sodium hydroxide 作用下， 反应 9.0h， 生成 (R)-2-methyl-2-((7-methyl-6a,7,8,9-tetrahydro-6H-[1,3]dioxolo[4',5':5,6]benzo[1,2-g]benzo[de]quinolin-11-yl)oxy)propanoic acid hydrochloride
  参考文献：
  名称：

  2-Haloaporphines as potent dopamine agonists

  摘要：

  The synthesis of 2-amino- and 2-halo-substituted aporphines is described. The key step is the substitution of a hydroxy group in the 2-position with an amino group effected by a Smiles rearrangement reaction of the 2-methylpropanamide derivative 6. The affinity of the new compounds for the dopamine D-2 receptor in the anterior pituitary gland was evaluated. 2-Fluoroapomorphine was the most potent compound, being 1.5 times more potent than (-)-apomorphine. The structure-activity relationships are discussed in relation to a previously proposed receptor model.

  DOI：

  10.1021/jm00126a009
• 作为产物：
  描述：

  蒂巴因 在 盐酸 、 氢溴酸 作用下， 反应 6.0h， 生成 (R)(-)-2,10,11-trihydroxyaporphine hydrobromide
  参考文献：
  名称：

  Aporphines。39.（R）-（-）-和（S）-（+）-2-羟基阿扑吗啡的合成，多巴胺受体结合和药理活性。

  摘要：

  由蒂巴因和球茎卡帕因合成2,10,11-三羟基aporphine（THA）的对映异构体（6aR和6aS），并通过与tri化竞争与（-）-阿扑吗啡[（-）-APO]和多巴胺进行体外药理学评价阿扑吗啡，ADTN和螺哌啶醇可与小腿尾状核的膜部分结合，并具有刺激腺苷酸环化酶的能力。在所有四个测试中，效能的等级顺序是（-）-APO大于（-）-THA远大于（+）-THA。因此，这些结果扩展了以下印象：对于与假定的多巴胺受体的相互作用，羟基磷灰石的6aR构型是优选的，并且与10，11-二羟基磷灰石相比2-羟基化降低了效能。

  DOI：

  10.1021/jm00350a021

文献信息

• Apomorphine inhibitors of amyloid-beta (Abeta) fibril formation and their use in amyloidosis based disease
  申请人：——

  公开号：US20030187011A1

  公开（公告）日：2003-10-02

  Described is a new class of small molecule inhibitors of amyloid &bgr; protein (A&bgr;) aggregation, based on apomorphine. These molecules target the nucleation phase of A&bgr; self-assembly and interfere effectively with aggregation of A&bgr; 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit A&bgr; amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active A&bgr; inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of A&bgr; into short nonfibrillar soluble assemblies, but inhibit A&bgr; fibrillization.

  描述的是一类基于阿朴吗啡的新型淀粉样&bgr;蛋白（A&bgr;）聚集小分子抑制剂。这些分子以 A&bgr; 自组装的成核阶段为目标，通过透射电子显微镜、硫黄素 T（ThT）荧光和速度沉降法测定，可有效干扰 A&bgr; 1-40 在体外聚集成淀粉样纤维。使用阿朴吗啡类似物进行的结构-活性研究表明，D环的10,11-二羟基取代是这些阿朴吗啡类药物发挥抑制作用的首选，而这些羟基的甲基化会降低它们的抑制效力。这些小分子抑制 A&bgr; 淀粉样纤维形成的能力似乎与它们在溶液中发生自身氧化的能力有关，这意味着一种自身氧化产物是活性 A&bgr; 抑制剂。沉降速度和电子显微镜研究表明，阿朴吗啡和类似物可促进 A&bgr; 的低聚作用，使其变成短的非纤维状可溶集合体，但会抑制 A&bgr; 的纤维化。
• RAMSBY, STEN;NEUMEYER, JOHN L.;GRIGORIADIS, DIMITRI;SEEMAN, PHILIP, J. MED. CHEM., 32,(1989) N, C. 1198-1201
  作者：RAMSBY, STEN、NEUMEYER, JOHN L.、GRIGORIADIS, DIMITRI、SEEMAN, PHILIP

  DOI：——

  日期：——
• METHODS OF TREATMENT, PREVENTION AND DIAGNOSIS
  申请人：The Walter and Eliza Hall Institute of Medical Research

  公开号：EP3873461A1

  公开（公告）日：2021-09-08
• APOMORPHINE INHIBITORS OF AMYLOID-BETA (ABETA) FIBRIL FORMATION AND THEIR USE IN AMYLOIDOSIS BASED DISEASE
  申请人：Lashuel A. Hilal

  公开号：US20080096909A1

  公开（公告）日：2008-04-24

  Described is a new class of small molecule inhibitors of amyloid β protein (Aβ) aggregation, based on apomorphine. These molecules target the nucleation phase of Aβ self-assembly and interfere effectively with aggregation of Aβ 1-40 into amyloid fibrils in vitro as determined by transmission electron microscopy, Thioflavin T (ThT) fluorescence, and velocity sedimentation. Structure-activity studies using apomorphine analogues demonstrate that 10,11-dihydroxy substitutions of the D ring are preferred for the inhibitory effectiveness of these aporphines, and that methylation of these hydroxyl groups reduces their inhibitory potency. The ability of these small molecules to inhibit Aβ amyloid fibril formation appears to be linked to their ability to undergo auto-oxidation in solution, implicating an auto-oxidation product as the active Aβ inhibitor. Sedimentation velocity and electron microscopy studies demonstrate that apomorphine and analogues facilitate oligomerization of Aβ into short nonfibrillar soluble assemblies, but inhibit Aβ fibrillization.
• Aporphines. 39. Synthesis, dopamine receptor binding, and pharmacological activity of (R)-(-)- and (S)-(+)-2-hydroxyapomorphine
  作者：John L. Neumeyer、G. W. Arana、Vishnu J. Ram、Nora S. Kula、Ross J. Baldessarini

  DOI：10.1021/jm00350a021

  日期：1982.8

  evaluated pharmacologically in vitro in comparison with (-)-apomorphine [(-)-APO] and dopamine by competition with tritiated apomorphine, ADTN, and spiroperidol for binding to a membrane fraction of calf caudate nucleus, as well as for ability to stimulate adenylate cyclase. In all four tests, the rank order of potency was (-)-APO greater than (-)-THA much greater than (+)-THA. Thus, these results extend

  由蒂巴因和球茎卡帕因合成2,10,11-三羟基aporphine（THA）的对映异构体（6aR和6aS），并通过与tri化竞争与（-）-阿扑吗啡[（-）-APO]和多巴胺进行体外药理学评价阿扑吗啡，ADTN和螺哌啶醇可与小腿尾状核的膜部分结合，并具有刺激腺苷酸环化酶的能力。在所有四个测试中，效能的等级顺序是（-）-APO大于（-）-THA远大于（+）-THA。因此，这些结果扩展了以下印象：对于与假定的多巴胺受体的相互作用，羟基磷灰石的6aR构型是优选的，并且与10，11-二羟基磷灰石相比2-羟基化降低了效能。