N-propylnororipavine | 948313-69-7

• 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-propylnororipavine
• 英文别名: R(-)-N-propyl-3-oxynororipavine；(4R,7aR,12bS)-7-methoxy-3-propyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-ol
• CAS: 948313-69-7
• 化学式: C₂₀H₂₃NO₃
• 分子量: 325.408
• InChiKey: QBZLVHXGFMIAPH-UAOJZALGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-propylnororipavine 在 甲烷磺酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 R(-)-2-(2-fluoroethoxy)-10-[(trifluoromethyl)sulfonyl]oxy-11-hydroxy-N-n-propylnoraporphine
  参考文献：
  名称：

  Synthesis and Evaluation of Fluorinated Aporphines: Potential Positron Emission Tomography Ligands for D₂ Receptors

  摘要：

  The 2-fluoroalkoxy-substituted catechol-aporphines 6, 8a-f and 11-mono-hydroxyaporphines 11a-e were synthesized and found to have high in vitro affinity and selectivity for the dopamine D-2 receptors. The catechol aporphines, 8b and 8d, and the monohydroxy aporphines, 11-ad, were identified as candidates for development as potential PET ligands.

  DOI：

  10.1021/ml1001689
• 作为产物：
  描述：

  蒂巴因 在 偶氮二甲酸二异丙酯 、 L-Selectride 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 苯 为溶剂， 生成 N-propylnororipavine
  参考文献：
  名称：

  Identification of fluorinated (R)-(−)-aporphine derivatives as potent and selective ligands at serotonin 5-HT2C receptor

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2018.11.050

文献信息

• [EN] 2-ALKOXY-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE 2-ALCOXY-11-HYDROXYAPORPHINE ET LEURS UTILISATIONS
  申请人：MCLEAN HOSPITAL CORP

  公开号：WO2011130530A1

  公开（公告）日：2011-10-20

  The invention features 2-alkoxy-l l-hydroxyaporphine derivatives that selectively bind D2high receptors. The compounds are useful for imaging D2high receptors and for the treatment of diseases, such as Parkinson's disease, sexual dysfunction, and depressive disorders.

  这项发明涉及选择性结合D2高亲和力受体的2-烷氧基-1-羟基吖啶衍生物。这些化合物可用于成像D2高亲和力受体以及用于治疗帕金森病、性功能障碍和抑郁症等疾病。
• R(-)-2-METHOXY-11-HYDROXYAPORPHINE AND DERIVATIVES THEREOF
  申请人：Neumeyer John L.

  公开号：US20110034446A1

  公开（公告）日：2011-02-10

  The invention features derivatives of R(−)-2-methoxy-11-hydroxyaporphines and methods of treating Parkinson's disease, sexual dysfunction, and depressive disorders therewith.

  这项发明涉及R（-）-2-甲氧基-11-羟基阿品啡衍生物及其用于治疗帕金森病、性功能障碍和抑郁症的方法。
• 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.
• Synthesis and neuropharmacological evaluation of esters of R(−)-N-alkyl-11-hydroxy-2-methoxynoraporphines
  作者：Yu-Gui Si、Yong-Kee Choi、Matthew P. Gardner、Frank I. Tarazi、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1016/j.bmcl.2008.11.025

  日期：2009.1

  We synthesized several esters of R(-)-N-alkyl-11-hydroxy-2-methoxynoraporphines, assessed their affinities at dopamine D-1 and D-2 receptors in rat forebrain tissue and quantified their effects on motor activity in normal adult male rats. Tested compounds displayed moderate to high affinities to D-2 receptors but low affinities to D-1 receptors. The most D-2-potent (K-i = 18.9 nM) and selective novel agent (>529-fold vs D-1 sites) was R(-)-2-methoxy-11-acetyloxy-N-n-propylnoraporphine (compound 4b). At moderate doses, the compound proved to have prolonged behavioral locomotor activity. (C) 2008 Elsevier Ltd. All rights reserved.