(-)-(R)-11-methoxyaporphine hydrochloride | 83207-97-0

• 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 hydrochloride
• 英文别名: (R)-(-)-11-methoxyaporphine hydrochloride；(R)-11-Methoxyaporphine Hydrochloride；(6aR)-11-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline;hydrochloride
• CAS: 83207-97-0
• 化学式: C₁₈H₁₉NO*ClH
• 分子量: 301.816
• InChiKey: ALEFABNGZZGZFN-XFULWGLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.87
• 重原子数：
  21
• 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：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-(R)-11-methoxyaporphine hydrochloride 在 palladium on activated charcoal 2,4,6-三甲基吡啶 、 盐酸 、 氢溴酸 、 氢气 、 四氯化锡 作用下， 以 乙醇 为溶剂， 50.0~120.0 ℃ 、310.27 kPa 条件下， 反应 38.33h， 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aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl.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：

  (R)-(-)-10-O-(1-phenyltetrazol-5-yl)-11-methoxyaporphine 以56%的产率得到
  参考文献：
  名称：

  CANNON, JOSEPH G.;MOHAN, PREM;BOJARSKI, JACEK;LONG, JOHN PAUL;BHATNAGAR, +, J. MED. CHEM., 31,(1988) N 2, 313-318

  摘要：

  DOI：

文献信息

• (S)-11-Hydroxy-10-methyl aporphine and pharmaceutical compositions containing it
  申请人：BRITISH TECHNOLOGY GROUP LTD

  公开号：EP0494777A1

  公开（公告）日：1992-07-15

  (S)-11-Hydroxy-10-methylaporphine and its physiologically acceptable salts show activity as 5-HT1A inhibitors and can be used as an antidote for effects of cocaine and as appetite suppressants.

  (S)-11-羟基-10-甲基吗啡及其生理上可接受的盐类具有 5-HT1A 抑制剂的活性，可用作可卡因的解毒剂和食欲抑制剂。
• 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.
• US5258384A
  申请人：——

  公开号：US5258384A

  公开（公告）日：1993-11-02