(R)-去甲阿朴可待因 | 478-77-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 中文名称: (R)-去甲阿朴可待因
• 英文名称: norapocodeine
• 英文别名: 10-methoxy-6aβ-aporphan-11-ol；(R)-Norapocodeine；(6aR)-10-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol
• CAS: 478-77-3
• 化学式: C₁₇H₁₇NO₂
• 分子量: 267.327
• InChiKey: DCQBVSOYNWLFKD-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-碘代丙烷 、 (R)-去甲阿朴可待因 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 (R)-(-)-N-isopropylnorapocodeine
  参考文献：
  名称：

  Synthesis and structural requirements of N-substituted norapomorphines for affinity and activity at dopamine D-1, D-2, and agonist receptor sites in rat brain

  摘要：

  A series of N-substituted analogues of (R)-(-)-norapomorphine were synthesized to study the optimal structural requirements of the N-alkyl side chain to interact with D-1 and D-2 dopaminergic receptors as well as dopamine (DA) agonist binding sites. Evaluations included testing the affinity of these compounds for DA receptor sites in rat striatal tissue and assessing stereotypy as a behavioral index of dopaminergic activity. The electronic, steric, and lipophilic properties of the N-alkyl side chain were found to be related to affinity, D-2 selectivity, and dopaminergic activity. All 11 compounds evaluated had relatively low affinity at D-1 sites. Optimum D-2 and agonist-site affinity as well as agonist activity were exhibited by N-cyclopropylmethyl (7) greater than or equal to N-allyl (8) greater than or equal to N-propyl (4) or N-ethyl (3) substituted compounds. Branching of the N-alkyl side chain as in N-isopropyl (5) and N-isobutyl (6) markedly reduced the D-2 affinity and activity, presumably due to steric effects. The N-trifluoroethyl (10) and N-pentafluoropropyl (11) derivatives had low affinity for all their dopamine receptor sites and no agonistic activity; evidently, the highly electronegative F atoms decrease basicity of the N atom and therefore decrease the ability of the N atom to be cationic at physiological pH, a proposed requirement for high-affinity binding to DA receptors.

  DOI：

  10.1021/jm00163a007
• 作为产物：
  描述：

  去甲可待因 在 草酸 作用下， 生成 (R)-去甲阿朴可待因
  参考文献：
  名称：

  阿朴吗啡和维生素的反应

  摘要：

  D-ch-N-β-羧基-Athauginsäure（VII），N-Nor-Apocodeins（XIII），Shoie jene des Apomorphins（XIIIb）和Verwandter Verbindungen bewiesen。模具制造商（XIb）的工作人员。

  DOI：

  10.1002/hlca.19550380746

文献信息

• Aporphines. 27. Mechanistic aspects of the rearrangement of thebaine and codeine analogs in methanesulfonic acid. Improved method for the synthesis of N-alkylated aporphines
  作者：Felix E. Granchelli、Crist N. Filer、Albert H. Soloway、John L. Neumeyer

  DOI：10.1021/jo01300a001

  日期：1980.6
• US7517853B2
  申请人：——

  公开号：US7517853B2

  公开（公告）日：2009-04-14
• US8822442B2
  申请人：——

  公开号：US8822442B2

  公开（公告）日：2014-09-02
• Synthesis and structural requirements of N-substituted norapomorphines for affinity and activity at dopamine D-1, D-2, and agonist receptor sites in rat brain
  作者：Yigong Gao、Vishnu J. Ram、Alexander Campbell、Nora S. Kula、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1021/jm00163a007

  日期：1990.1

  A series of N-substituted analogues of (R)-(-)-norapomorphine were synthesized to study the optimal structural requirements of the N-alkyl side chain to interact with D-1 and D-2 dopaminergic receptors as well as dopamine (DA) agonist binding sites. Evaluations included testing the affinity of these compounds for DA receptor sites in rat striatal tissue and assessing stereotypy as a behavioral index of dopaminergic activity. The electronic, steric, and lipophilic properties of the N-alkyl side chain were found to be related to affinity, D-2 selectivity, and dopaminergic activity. All 11 compounds evaluated had relatively low affinity at D-1 sites. Optimum D-2 and agonist-site affinity as well as agonist activity were exhibited by N-cyclopropylmethyl (7) greater than or equal to N-allyl (8) greater than or equal to N-propyl (4) or N-ethyl (3) substituted compounds. Branching of the N-alkyl side chain as in N-isopropyl (5) and N-isobutyl (6) markedly reduced the D-2 affinity and activity, presumably due to steric effects. The N-trifluoroethyl (10) and N-pentafluoropropyl (11) derivatives had low affinity for all their dopamine receptor sites and no agonistic activity; evidently, the highly electronegative F atoms decrease basicity of the N atom and therefore decrease the ability of the N atom to be cationic at physiological pH, a proposed requirement for high-affinity binding to DA receptors.
• Die Konfiguration des Apomorphins und verwandter Verbindungen
  作者：H. Corrodi、E. Hardegger

  DOI：10.1002/hlca.19550380746

  日期：——

  Durch oxydativen Abbau zu N-β-Carboxyäthyl-D-asparaginsäure (VII) wurde die Konfiguration des N-Nor-apocodeins (XIII), sowie jene des Apomorphins (XIIIb) und verwandter Verbindungen bewiesen. Die daraus gezogenen Folgerungen bezüglich der Konfiguration des Morphins (XIb) wurden inzwischen von anderer Seite bestätigt.

  D-ch-N-β-羧基-Athauginsäure（VII），N-Nor-Apocodeins（XIII），Shoie jene des Apomorphins（XIIIb）和Verwandter Verbindungen bewiesen。模具制造商（XIb）的工作人员。