(R)-(-)-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]-11-hydroxyaporphine | 1009100-09-7

• 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: (R)-(-)-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]-11-hydroxyaporphine
• 英文别名: 11-hydroxy-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]aporphine；(6aR)-2-methoxy-10-[(trifluoromethyl)sulfonyl]-11-hydroxyaporphine；2-methoxy-10-O-[(trifluoromethyl)sulfonyl]-11-hydroxyaporphine；[(6aR)-11-hydroxy-2-methoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-10-yl] trifluoromethanesulfonate
• CAS: 1009100-09-7
• 化学式: C₁₉H₁₈F₃NO₅S
• 分子量: 429.417
• InChiKey: HNILVDQKLNNUHR-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  84.4
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (R)-(-)-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]-11-hydroxyaporphine 在 palladium on activated charcoal 、 ammonium acetate 、 potassium carbonate 、 magnesium 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (R)-(-)-2-methoxy-11-((4-fluorobenzyl)oxy)aporphine
  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
• 作为产物：
  描述：

  蒂巴因 在 甲烷磺酸 、 L-Selectride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (R)-(-)-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]-11-hydroxyaporphine
  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

• Facile Synthesis of 11-Hydroxy-2-methoxyaporphine: A Potential Dopamine D₁ Receptor Ligand
  作者：Yu-Gui Si、John Neumeyer

  DOI：10.1055/s-2007-990902

  日期：2007.12

  11-Hydroxy-2-methoxyaporphine was synthesized from oripavine in three steps with an overall yield of 37.8%. The key step involved the palladium on carbon catalyzed reduction of 11-hydroxy-2-methoxy-10- O-[(trifluoromethyl)sulfonyl]aporphine using magnesium metal in methanol at room temperature in the presence of ammonium acetate.

  11-Hydroxy-2-methoxyaporphine 由东罂粟碱分三步合成，总收率为 37.8%。关键步骤涉及钯碳催化还原 11-羟基-2-甲氧基-10-O-[(三氟甲基)磺酰基]阿朴啡，在乙酸铵存在下，在室温下使用金属镁在甲醇中进行还原。
• [EN] R(-)-2-METHOXY-11-HYDROXYAPORPHINE AND DERIVATIVES THEREOF<br/>[FR] R(-)-2-MÉTHOXY-11-HYDROXYAPORPHINE ET SES DÉRIVÉS
  申请人：MCLEAN HOSPITAL CORP

  公开号：WO2009009083A1

  公开（公告）日：2009-01-15

  The invention features derivatives of R(-)-2-methoxy-l 1- hydroxyaporphines and methods of treating Parkinson's disease, sexual dysfunction, and depressive disorders therewith.

  本发明涉及R(-)-2-甲氧基-11-羟基阿波啡的衍生物及其用于治疗帕金森病、性功能障碍和抑郁障碍的方法。
• Synthesis and pharmacological investigation of novel 2-aminothiazole-privileged aporphines
  作者：Zhili Liu、Xuetao Chen、Leiping Yu、Xuechu Zhen、Ao Zhang

  DOI：10.1016/j.bmc.2008.05.077

  日期：2008.7

  A series of apomorphine ((-)-1, APO)-derived analogues ((+/-)-3, (-)-4-(-)-6) were designed and synthesized by hybridizing APO with a privileged 2-aminothiazole functionality which was lent from the orally available anti-parkinsonian drug, pramipexole (2). Among these hybridized compounds, catecholic aporphine (-)-6 shows good affinity at the D(2) receptor with K(i) of 328nM, slightly less potent (3-fold)

  通过将APO与特有的2-氨基噻唑杂交，设计并合成了一系列阿朴吗​​啡（（-）-1，APO）衍生的类似物（（+/-）-3，（-）-4-（-）-6）口服抗帕金森病药物普拉克索（2）提供的功能性。在这些杂交的化合物中，儿茶酚卟啉（-）-6在D（2）受体上具有328nM的K（i）的良好亲和力，效力稍弱（3倍），但对D（1）受体的选择性比母体化合物，APO。尽管在D（2）受体上具有降低的亲和力，但紫粉15和18在D（1）和5-HT（1A）受体上均显示出显着的效力。前一种化合物在两个受体上均等价（分别为K（i）：116和151nM），而后者在D（1）上的效价（K（i）：78nM）是5-HT的8倍。 （1A）受体（K（i）：640nM）。
• 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。
• 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.