(-)-2,10,11-trihydroxy-N-propargylnoraporphine | 79640-93-0

• 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: (-)-2,10,11-trihydroxy-N-propargylnoraporphine
• 英文别名: (6aR)-6-prop-2-ynyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-2,10,11-triol
• CAS: 79640-93-0
• 化学式: C₁₉H₁₇NO₃
• 分子量: 307.349
• InChiKey: GVUPQEKJRZBHBF-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  63.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酰溴 、 (-)-2,10,11-trihydroxy-N-propargylnoraporphine 在 三氟乙酸 作用下， 反应 2.0h， 生成
  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：

  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

文献信息

• 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
  作者：John L. Neumeyer、George W. Arana、Say Jong Law、Jeffrey S. Lamont、Nora S. Kula、Ross J. Baldessarini

  DOI：10.1021/jm00144a014

  日期：1981.12

  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.