N-propylnorthebaine | 88840-30-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: N-propylnorthebaine
• 英文别名: (4R,7aR,12bS)-7,9-dimethoxy-3-propyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinoline
• CAS: 88840-30-6
• 化学式: C₂₁H₂₅NO₃
• 分子量: 339.434
• InChiKey: HFWUCIYTZZHAGD-NQERJWCQSA-N

物化性质

• 熔点：
  134-136 °C
• 沸点：
  488.9±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)
• 溶解度：
  溶于氯仿

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-propylnorthebaine 以86%的产率得到northebaine
  参考文献：
  名称：

  Mucor piriformis, an efficient N-dealkylating reagent for thebaine and its N-variants

  摘要：

  Mucor piriformis very efficiently N-dealkylates thebaine, its N-substituted variants and Diels-Alder adducts.

  DOI：

  10.1039/p19940000911
• 作为产物：
  描述：

  蒂巴因 在 sodium thiophenolate 作用下， 以 氯仿 、 乙腈 、 丁酮 为溶剂， 反应 18.0h， 生成 N-propylnorthebaine
  参考文献：
  名称：

  A Convenient Method for Replacing theN-Methyl Group of Morphine, Codeine, and Thebaine by Other Alkyl Groups

  摘要：

  DOI：

  10.1055/s-1983-30523

文献信息

• Synthesis of 2-Fluoro-11-hydroxy-<i>N</i>-propylnoraporphine:  A Potential Dopamine D₂ Agonist
  作者：Ao Zhang、Csaba Csutoras、Rushi Zong、John L Neumeyer

  DOI：10.1021/ol051010d

  日期：2005.7.1

  The key steps included the Pd-catalyzed 3-dehydroxylation of 14-hydroxymorphine, S(N)2 substitution of Ts(-) by F(-), and CH(3)SO(2)OH-promoted rearrangement of the substituted morphinandiene. The dopamine binding affinity of this compound was also investigated on rat brain membranes, and as expected, this compound displayed high affinity and selectivity at the D(2) receptor.

  [结构：见文字]。从蒂巴因以13个步骤合成2-氟-11-羟基-N-丙基诺拉啡4（2-F-11-OH-NPa），总产率为1.35％。关键步骤包括Pd催化的14-羟基吗啡的3-脱羟基反应，Ts（-）的S（N）2被F（-）取代以及CH（3）SO（2）OH促进的吗啡二烯的重排。还研究了该化合物在大鼠脑膜上的多巴胺结合亲和力，并且正如预期的那样，该化合物在D（2）受体上显示出高亲和力和选择性。
• Synthesis of New Apomorphine Derivatives Containing Halogen (CI and Br) in RING-D#
  作者：Sándor Hosztafi、Sándor Makleit

  DOI：10.1080/00397919608003811

  日期：1996.11

  Abstract A series of 8-halogen- (Cl,Br)-substituted apocodeines was prepared by the rearrangement of the corresponding 1-halogen-substituted codeines. O-demethylation of the apocodeines yielded the 8-halogenoapomorphines. 8-bromo-substituted morphothebaine derivatives have been conveniently prepared by direct bromination.

  摘要 通过对相应的1-卤素取代的可待因进行重排，制备了一系列8-卤素-(Cl,Br)-取代的阿朴可待因。阿朴可待因的 O-去甲基化产生了 8-卤代阿朴吗啡。通过直接溴化可以方便地制备 8-溴取代的吗啡蒂巴因衍生物。
• R-(−)-N-alkyl-11-hydroxy-10-hydroxymethyl- and 10-methyl-aporphines as 5-HT1A receptor ligands
  作者：Yu-Gui Si、Matthew P. Gardner、Frank I. Tarazi、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1016/j.bmcl.2007.05.057

  日期：2007.8

  Several N-substituted-11-hydroxy-10-hydroxymethyl- and 11-hydroxy-10-methylaporphines were synthesized and their binding affinities at dopamine D, and D, receptors and serotonin 5-HT1A and 5-HT2A receptors in rat forebrain tissue were evaluated. Tested compounds displayed moderate to high affinity to 5-HT1A receptors but low affinity to D, and D-2 receptors. The most potent novel 5-HT1A agent was R-(-)-N-methyl-10-hydroxymethyl-11-hydroxyaporphine. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and Dopamine Receptor Affinities of <i>N</i>-Alkyl-11-hydroxy-2-methoxynoraporphines: <i>N</i>-Alkyl Substituents Determine D1 versus D2 Receptor Selectivity
  作者：Yu-Gui Si、Matthew P. Gardner、Frank I. Tarazi、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1021/jm701045j

  日期：2008.2.1

  We developed a procedure to synthesize a series of N-alkyl-2-methoxy-11-hydroxyhoraporphines from thebaine and evaluated their binding affinities at dopamine D-1 and D-2 receptors in rat forebrain tissue. At D-2 receptors, the most potent 10,11-catechol-aporphine was (R)-(-)-2-methoxy-N-n-propylnorapomorphine (D-2, K-i = 1.3 nM; D-1, K-i = 6450 nM), and the most selective and potent 11-monohydroxy aporphine was (R)-(-)-2-methoxy-11-hydroxy-N-n-propylnoraporphine (D-2, K-i = 44 nM; D-1, K-i = 1690 nM). In contrast, the N-methyl congeners (R)-(-)-2-methoxy-11-hydroxy: N-methyl-aporphine (D-1 vs D-2, K-i = 46 vs 235 nM) showed higher D-1 than D2 affinity, indicating that N-alkyl substituents have major effects on D2 affinity and D-2/D-1 selectivity in such 2-methoxy-11-monohydroxy-substituted aporphines.
• Identification of fluorinated (R)-(−)-aporphine derivatives as potent and selective ligands at serotonin 5-HT2C receptor
  作者：Yulong Xu、Anna W. Sromek、John L. Neumeyer

  DOI：10.1016/j.bmcl.2018.11.050

  日期：2019.1

  A series of novel aporphine derivatives were synthesized for initial screening at the 5-HT2 receptor subtypes. Among them, Compounds 11a and 11b were identified as potent 5-HT2C hit ligands with high selectivity over other 5-HT2 receptor subtypes. Molecular docking study revealed that compounds 11a and 11b formed two key interactions with the binding site of 5-HT2C receptor, including a salt-bridge to D3.32 and a H-bond interaction with N6.55.