normorphothebaine hydrochloride | 61752-20-3

• 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: normorphothebaine hydrochloride
• CAS: 61752-20-3
• 化学式: C₁₇H₁₇NO₃*ClH
• 分子量: 319.788
• InChiKey: IOBJJHUYYCNFIE-BTQNPOSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  61.72
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  normorphothebaine hydrochloride 在 氢溴酸 、 碳酸氢钠 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 21.0h， 生成 (-)-2,10,11-trihydroxy-N-propargylnoraporphine
  参考文献：
  名称：

  Aporphines. 36. Dopamine receptor interactions of trihydroxyaporphines. Synthesis, radioreceptor binding, and striatal adenylate cyclase stimulation of 2,10,11-trihydroxyaporphines in comparison with other hydroxylated aporphines

  摘要：

  The presence of the A ring of aporphines and the addition of substituents to it and to other portions of the aporphine ring systems can extend explorations of the dimensions and other characteristics of the dopamine receptors. Accordingly, the synthesis and some physical and pharmacological properties of a series of (-)-2,10,11-trihydroxyaporphines (3a-g) are described. Structure-activity relationships among mono-, di-, and trihydroxyaporphines were evaluated against the high-affinity (nanomolar) binding of [3H]apomorphine (APO) and [3H]spiroperidol (SPR) with a subcellular fraction (P4) of caudate nucleus from bovine brain. In addition, DA-sensitive adenylate cyclase activity was evaluated in homogenates of rat brain striatal tissue. The rank order of displacement of [3H]APO by potent aporphines (IC50 less than or equal to 30 nM) correlated approximately with their ability to stimulate cyclic AMP synthesis. Potency orders against two ligands were dissimilar; for example, increasing the size of N6-alkyl substituents increased potency vs. [3H]SPR but not vs. [3H]APO binding. Moreover, [3H]SPR binding correlated poorly with cyclase activity or [3H]APO binding, suggesting a closer relationship of [3H]APO binding to dopamine-sensitive adenylate cyclase activity.

  DOI：

  10.1021/jm00144a014
• 作为产物：
  描述：

  apocodeine N-oxide*HCl 在 ferrous(II) sulfate heptahydrate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 normorphothebaine hydrochloride
  参考文献：
  名称：

  在阿朴啡骨架上通过直接 N-取代合成具有药理活性的阿朴吗啡

  摘要：

  已经开发了一种用于直接 N-取代阿朴啡的方法，包括 N-氧化-N-脱保护-N-烷基化序列。发现该方法对环 A 或 D 的取代模式的变化不敏感，因此推测它也适用于全合成和天然来源的阿朴啡。

  DOI：

  10.1055/s-2008-1078494

文献信息

• Aporphines. 34. (-)-2,10,11-Trihydroxy-N-n-propylnoraporphine, a novel dopaminergic aporphine alkaloid with anticonvulsant activity
  作者：J. L. Neumeyer、S. J. Law、B. Meldrum、G. Anlezark、K. J. Watling

  DOI：10.1021/jm00139a027

  日期：1981.7

  (-)-2,10,11-Trihydroxy-N-n-propylnoraporphine (TNPA,2c) has been synthesized from thebaine (3a), via northebaine (3b), normorphothebaine (2a), and alkylation to the N-propyl derivative 2b. O-Demethylation gave the desired product 2c. Compound 2c showed activity comparable to its 10,11-dihyroxy counterpart (NPA, 1b) on the stimulation of dopamine-sensitive adenylate cyclase in carp retinal homogenates. The evaluation of 2c on audiogenic seizures in mice, in the protection against paroxysimal EEG and myoclonic response to photic stimulation in the baboon, revealed a similar pharmacological profile in comparison to NPA and apomorphine, with TNPA showing a prolonged duration of action in abolishing myoclonic response to photic stimulation in the baboon.

  (-)-2,10,11-三羟基-N-正丙基去甲阿朴啡（TNPA，2c）通过从thbaine（3a）经去甲thbaine（3b）、去甲阿扑吗啡（2a）及烷基化反应制得N-正丙基衍生物2b，再经O-去甲基化反应得到目标产物2c。化合物2c在刺激鲤鱼视网膜匀浆中多巴胺敏感的腺苷酸环化酶活性方面，与具有10,11-二羟基取代的类似物（NPA，1b）显示出相当的活性。在对小鼠听觉诱发惊厥的评估，以及对狒狒中光刺激引发的阵发性脑电图和肌阵挛反应的保护作用研究中，化合物2c与NPA和阿扑吗啡相比表现出相似的药理学特性，且TNPA在消除狒狒中光刺激引发的肌阵挛反应方面表现出更长的作用持续时间。