(-)-(R)-11-methoxyaporphine | 121617-59-2

• 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)-11-methoxyaporphine
• 英文别名: (R)-(-)-11-methoxyaporphine；11-Methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline；(6aR)-11-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• CAS: 121617-59-2
• 化学式: C₁₈H₁₉NO
• 分子量: 265.355
• InChiKey: HJSGUUPPOBQDHU-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-(R)-11-methoxyaporphine 在 氢溴酸 作用下， 反应 3.0h， 以74%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
• 作为产物：
  描述：

  3-O-(1-phenyltetrazol-5-yl)morphine 在 palladium on activated charcoal 甲烷磺酸 、 氢气 、 溶剂黄146 作用下， 以 乙醚 为溶剂， 25.0~95.0 ℃ 、310.27 kPa 条件下， 反应 52.5h， 生成 (-)-(R)-11-methoxyaporphine
  参考文献：
  名称：

  5-HT 1A受体拮抗作用：（R）-（-）-8，11-二甲氧基诺拉啡的N-烷基衍生物。

  摘要：

  以前的发现提示，芳环上的对二甲氧基取代模式可在某些环系统中保留多巴胺能激动剂效应，其中邻苯二酚衍生物是有效的多巴胺能激动剂，将8,11-二甲氧基取代模式引入了Aph环中。在阿扑吗啡中的10,11-二羟基部分的位置。适当的吗啡衍生物的酸催化重排为阿福啡环系统提供了6a不对称中心立体化学完整性的保留。通过催化氢解其苯基四唑基醚除去位置10处的羟基。用三氟乙酰基亚硫酸氢盐在8位以高收率碘化所得的11-羟基阿扑吗啡的甲基醚。这是合成碘化的海豚碱衍生物的第一个说明。通过与甲醇钠和碘化亚铜反应，将8-碘取代基替换为甲氧基。N-甲基靶标化合物7或Nn-丙基衍生物8均未显示出多巴胺能或血清素能激动作用。但是，有7种药物具有受体结合特性和其他药理特性，表明它可能是5-HT1A受体拮抗剂。

  DOI：

  10.1021/jm00128a044

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
• Aporphines. 42. Synthesis of (R)-(-)-11-hydroxyaporphines
  作者：Vishnu J. Ram、John L. Neumeyer

  DOI：10.1021/jo00143a050

  日期：1982.10
• (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.
• (R)-(-)-10-Methyl-11-hydroxyaporphine: a highly selective serotonergic agonist
  作者：Joseph G. Cannon、Prem Mohan、Jacek Bojarski、John Paul Long、Ranbir K. Bhatnagar、Paul A. Leonard、Jan R. Flynn、Tapan K. Chatterjee

  DOI：10.1021/jm00397a007

  日期：1988.2

  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.
• CANNON, JOSEPH G.;JACKSON, HENRY;LONG, JOHN PAUL;BHATNAGAR, RANBIR K., J. MED. CHEM., 32,(1989) N, C. 1959-1962
  作者：CANNON, JOSEPH G.、JACKSON, HENRY、LONG, JOHN PAUL、BHATNAGAR, RANBIR K.

  DOI：——

  日期：——