(-)-11-Hydroxyaporphine | 88247-20-5

• 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: (-)-11-Hydroxyaporphine
• 英文别名: (-)-(R)-11-hydroxyaporphine；(R)-(-)-11-hydroxyaporphine；R-(-)-11-hydroxyaporphine；(R)-(-)-hydroxyaporphine；(R)-11-hydroxyaporphine；R(-)-11-OH-aporphine；(R)-6-Methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol；(6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol
• CAS: 88247-20-5
• 化学式: C₁₇H₁₇NO
• 分子量: 251.328
• InChiKey: PCGXWSCASZVBJT-CQSZACIVSA-N

物化性质

• 熔点：
  232-234 °C
• 沸点：
  433.6±33.0 °C(Predicted)
• 密度：
  1.212±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 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：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-11-Hydroxyaporphine 在 palladium on activated charcoal 2,4,6-三甲基吡啶 、 盐酸 、 氢气 、 四氯化锡 作用下， 以 乙醇 为溶剂， 50.0~100.0 ℃ 、310.27 kPa 条件下， 反应 34.33h， 生成 (-)-(R)-11-hydroxy-10-methylaporphine
  参考文献：
  名称：

  (R)-(-)-10-Methyl-11-hydroxyaporphine: a highly selective serotonergic agonist

  摘要：

  Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

  DOI：

  10.1021/jm00397a007
• 作为产物：
  描述：

  3-deoxymorphine 在 甲烷磺酸 作用下， 反应 0.25h， 以67%的产率得到(-)-11-Hydroxyaporphine
  参考文献：
  名称：

  方便地合成海豚碱衍生物

  摘要：

  利用钯催化的反应的新的有效合成路线，从天然吗啡4提供（R）-11-羟基-10-甲基aporphine 2和（R）-11-羟基aporphine 3。

  DOI：

  10.1039/c39920000845

文献信息

• Aporphines as antagonists of dopamine D-1 receptors
  作者：John M. Schaus、Robert D. Titus、Mark M. Foreman、Norman R. Mason、Lewis L. Truex

  DOI：10.1021/jm00164a022

  日期：1990.2

  The aporphine alkaloids are a class of compounds known to possess activity at both D-1 and D-2 dopamine receptors. (R)-Apomorphine and (S)-bulbocapnine are examples of compounds which have agonist and antagonist activity, respectively, at D-1 receptors. A series of optically pure aporphines was synthesized and their activity at D-1 and D-2 dopamine receptors was studied. The (R)-aporphines uniformly

  紫花碱生物碱是一类已知对D-1和D-2多巴胺受体均具有活性的化合物。（R）-阿扑吗啡和（S）-布尔卡因胺是分别对D-1受体具有激动剂和拮抗剂活性的化合物的实例。合成了一系列光学纯的磷灰石，并研究了它们对D-1和D-2多巴胺受体的活性。（R）-海豚对D-1和D-2受体的亲和力均比其S对映体更高。根据先前的研究，发现二羟基化合物（R）-阿扑吗啡是D-1激动剂。在C-11处具有单个羟基的紫杉烷是D-1受体的拮抗剂。相应的甲氧基化合物在多巴胺受体上实际上是无活性的。最有效的化合物是（R）-11-羟基吗啡（R-14）和（R）-10-溴-11-羟基吗啡（R-26），比D-拮抗剂更有效，但不如B-1-B拮抗剂。制定了磷灰石与D-1受体结合的模型，其中受体与碱性氮和磷灰石的C-11羟基之间的结合相互作用是高亲和力与受体结合所必需的。C-6a处的绝对构型决定了N-6个孤对的方向，结合对于6aR系列而言是最佳
• 2-alkoxy-11-hydroxyaporphine derivatives and uses thereof
  申请人：The McLean Hospital Corporation

  公开号：US10081600B2

  公开（公告）日：2018-09-25

  The invention features 2-alkoxy-11-hydroxyaporphine derivatives that selectively bind D2high receptors. The compounds are useful for imaging D2high receptors and for the treatment of diseases, such as Parkinson's disease, sexual dysfunction, and depressive disorders.

  本发明具有选择性结合 D2high 受体的 2-烷氧基-11-羟基吗啡衍生物。这些化合物可用于 D2high 受体成像和疾病治疗，如帕金森病、性功能障碍和抑郁症。
• R(-)-11-hydroxyaporphine derivatives and uses thereof
  申请人：Neumeyer L. John

  公开号：US20060040900A1

  公开（公告）日：2006-02-23

  The invention features derivatives of R(—)-11-hydroxyaporphines and methods of treating Parkinson's disease, sexual dysfunction, and depressive disorders therewith.

  本发明的特点是 R(-)-11-羟基阿扑啡的衍生物以及用其治疗帕金森病、性功能障碍和抑郁障碍的方法。
• R-(−)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands
  作者：Yu-Gui Si、Matthew P. Gardner、Frank I. Tarazi、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1016/j.bmcl.2007.05.057

  日期：2007.8

  Several N-substituted-11-hydroxy-10-hydroxymethyl- and 11-hydroxy-10-methylaporphines were synthesized and their binding affinities at dopamine D, and D, receptors and serotonin 5-HT1A and 5-HT2A receptors in rat forebrain tissue were evaluated. Tested compounds displayed moderate to high affinity to 5-HT1A receptors but low affinity to D, and D-2 receptors. The most potent novel 5-HT1A agent was R-(-)-N-methyl-10-hydroxymethyl-11-hydroxyaporphine. (c) 2007 Elsevier Ltd. All rights reserved.
• (R)-11-Hydroxy- and (R)-11-Hydroxy-10-methylaporphine: Synthesis, Pharmacology, and Modeling of D2A and 5-HT1A Receptor Interactions
  作者：Martin H. Hedberg、Anette M. Johansson、Gunnar Nordvall、Ari Yliniemela、Hong Bing Li、Arnold R. Martin、Stephan Hjorth、Lena Unelius、Staffan Sundell、Uli Hacksell

  DOI：10.1021/jm00004a011

  日期：1995.2

  (R)-11-Hydroxyaporphine (2) and (R)-11-hydroxy-10-methylaporphine (3) were synthesized from natural morphine by using new, short, and efficient synthetic sequences. The dopaminergic and serotonergic effects of 2 and 3 were evaluated by use of in vitro and in vivo test systems. The results indicate that 3 is a potent, selective, and efficacious 6-HT1A receptor agonist. In contrast, 2 is a partial 5-HT1A receptor agonist of low potency which has affinity also for central D-1 and D-2A receptors. The differences in pharmacological profiles were rationalized by modeling of ligand-receptor interactions using homology-based receptor models of the 6-HT1A and D-2A receptor binding site. The selective and pronounced serotonergic effects of 3 appear to be due to the CIO-methyl group, which is accommodated by a lipophilic pocket in the 5-HT1A receptor. In contrast, the C10-methyl group of 3 is not accommodated by the binding site model of the D-2A receptor.