R(-)-2-methoxy-11-hydroxy-N-butylnoraporphine | 1012084-78-4

• 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-11-hydroxy-N-butylnoraporphine
• 英文别名: (6aR)-6-butyl-2-methoxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-ol
• CAS: 1012084-78-4
• 化学式: C₂₁H₂₅NO₂
• 分子量: 323.435
• InChiKey: GQIZBYSOZMBSBW-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  R-(-)-N-butyl-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]-11-hydroxynoraporphine 在 palladium on activated charcoal ammonium acetate 、 magnesium 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以55%的产率得到R(-)-2-methoxy-11-hydroxy-N-butylnoraporphine
  参考文献：
  名称：

  Synthesis and Dopamine Receptor Affinities of N-Alkyl-11-hydroxy-2-methoxynoraporphines: N-Alkyl Substituents Determine D1 versus D2 Receptor Selectivity

  摘要：

  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.

  DOI：

  10.1021/jm701045j

文献信息

• [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。
• 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。
• US8431591B2
  申请人：——

  公开号：US8431591B2

  公开（公告）日：2013-04-30
• 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.