N-propyl-3-O-[(trifluoromethyl)sulfonyl]nororipavine | 948313-71-1

• 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-propyl-3-O-[(trifluoromethyl)sulfonyl]nororipavine
• 英文别名: R(-)-N-propyl-3-[(trifluoromethyl)sulfonyl]oxynororipavine；3-O-((trifluoromethyl)sulfonyl)-N-n-propylnorthebaine；[(4R,7aR,12bS)-7-methoxy-3-propyl-2,4,7a,13-tetrahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-9-yl] trifluoromethanesulfonate
• CAS: 948313-71-1
• 化学式: C₂₁H₂₂F₃NO₅S
• 分子量: 457.471
• InChiKey: POZVNHAYWSRAIE-UAOJZALGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  73.4
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-propyl-3-O-[(trifluoromethyl)sulfonyl]nororipavine 在 palladium 10% on activated carbon 甲烷磺酸 、 ammonium acetate 、 magnesium 作用下， 反应 2.0h， 生成 MCL-536 hydrochloride
  参考文献：
  名称：

  [EN] 2-ALKOXY-11-HYDROXYAPORPHINE DERIVATIVES AND USES THEREOF
  [FR] DÉRIVÉS DE 2-ALCOXY-11-HYDROXYAPORPHINE ET LEURS UTILISATIONS

  摘要：

  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。

  公开号：

  WO2011130530A1
• 作为产物：
  描述：

  蒂巴因 在 偶氮二甲酸二异丙酯 、 L-Selectride 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 苯 为溶剂， 生成 N-propyl-3-O-[(trifluoromethyl)sulfonyl]nororipavine
  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

• 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 Evaluation of Fluorinated Aporphines: Potential Positron Emission Tomography Ligands for D₂ Receptors
  作者：Anna W. Sromek、Yu-Gui Si、Tangzhi Zhang、Susan R. George、Philip Seeman、John L. Neumeyer

  DOI：10.1021/ml1001689

  日期：2011.3.10

  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.
• 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 binding studies of 2-O- and 11-O-substituted N-alkylnoraporphines
  作者：Yu-Gui Si、Matthew P. Gardner、Frank I. Tarazi、Ross J. Baldessarini、John L. Neumeyer

  DOI：10.1016/j.bmcl.2008.06.016

  日期：2008.7

  We synthesized several novel 2-O- or 11-O-substituted N-alkylnoraporphines and assessed their affinities at dopamine D-1 and D-2, and serotonin 5-HT1A receptors in rat forebrain tissue. Tested compounds displayed moderate to high affinities to D-2 receptors but low affinities to D-1 and 5HT(1A) receptors. The findings accord with previous evidence of a lipophilic cavity on the surface of the D-2 receptor to accommodate N-alkyl moieties of aporphines. The most D-2- potent (K-i = 97 nM) and selective novel agent (> 100-fold vs. D-1 and 5-HT1A sites) was R(-)-2-(2-hydroxyethoxy)-11-hydroxy-N-n-propylnoraporphine (compound 11). (c) 2008 Elsevier Ltd. All rights reserved.
• 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.