(-)-(R)-11-benzyloxycarbonylaporphine | 264262-03-5

• 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)-11-benzyloxycarbonylaporphine
• 英文别名: benzyl (6aR)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline-11-carboxylate
• CAS: 264262-03-5
• 化学式: C₂₅H₂₃NO₂
• 分子量: 369.463
• InChiKey: BBTLSPLOTBFYIH-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-(R)-11-benzyloxycarbonylaporphine 在 10percent Pd/C PPA 、 氢气 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 5.5h， 生成 (6S,14R)-6,13-dimethyl-13-azapentacyclo[12.3.1.05,17.07,16.010,15]octadeca-1(17),2,4,7(16),8,10(15)-hexaen-6-ol
  参考文献：
  名称：

  Derivatives of (R)-1,11-Methyleneaporphine:  Synthesis, Structure, and Interactions with G-Protein Coupled Receptors

  摘要：

  The design and synthesis of a well-characterized novel ring system, (R)-lambda 1,11-methyleneaporphine [(R)-4], and 15 derivatives thereof are presented. The addition of various nucleophiles to (R)-lambda 1,11-carbonylaporphine [(R)-11] or to the 1,11-hydroxymethyleneaporphine epimers gave separable mixtures of epimers. The epimeric ratios obtained in most reactions seem to be a result of steric factors directing the nucleophilic attack. The structure of the epimers was determined by a combination of X-ray crystallography (5 derivatives), NMR spectroscopy, and chemical correlation. Interesting and diverse pharmacological profiles of the derivatives were revealed through binding studies at serotonin 5-HT7 and 5-HT1A receptors as well as at dopamine D-2A receptors. Two derivatives appeared to be selective 5-HT7 receptor antagonists. It is evident from our results that the novel ring system [(R)-4] provides a useful complement to other scaffolds available to medicinal chemists involved in studies of GPC receptors.

  DOI：

  10.1021/jm9911433
• 作为产物：
  描述：

  一氧化碳 、 Trifluoro-methanesulfonic acid (R)-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinolin-11-yl ester 、 苯甲醇 在 palladium diacetate 、 四甲基乙二胺 、 1,3-双(二苯基膦)丙烷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (-)-(R)-11-benzyloxycarbonylaporphine
  参考文献：
  名称：

  Derivatives of (R)-1,11-Methyleneaporphine:  Synthesis, Structure, and Interactions with G-Protein Coupled Receptors

  摘要：

  The design and synthesis of a well-characterized novel ring system, (R)-lambda 1,11-methyleneaporphine [(R)-4], and 15 derivatives thereof are presented. The addition of various nucleophiles to (R)-lambda 1,11-carbonylaporphine [(R)-11] or to the 1,11-hydroxymethyleneaporphine epimers gave separable mixtures of epimers. The epimeric ratios obtained in most reactions seem to be a result of steric factors directing the nucleophilic attack. The structure of the epimers was determined by a combination of X-ray crystallography (5 derivatives), NMR spectroscopy, and chemical correlation. Interesting and diverse pharmacological profiles of the derivatives were revealed through binding studies at serotonin 5-HT7 and 5-HT1A receptors as well as at dopamine D-2A receptors. Two derivatives appeared to be selective 5-HT7 receptor antagonists. It is evident from our results that the novel ring system [(R)-4] provides a useful complement to other scaffolds available to medicinal chemists involved in studies of GPC receptors.

  DOI：

  10.1021/jm9911433

文献信息

• Derivatives of (<i>R</i>)-1,11-Methyleneaporphine:  Synthesis, Structure, and Interactions with G-Protein Coupled Receptors
  作者：Tero Linnanen、Magnus Brisander、Lena Unelius、Göran Sundholm、Uli Hacksell、Anette M. Johansson

  DOI：10.1021/jm9911433

  日期：2000.4.6

  The design and synthesis of a well-characterized novel ring system, (R)-lambda 1,11-methyleneaporphine [(R)-4], and 15 derivatives thereof are presented. The addition of various nucleophiles to (R)-lambda 1,11-carbonylaporphine [(R)-11] or to the 1,11-hydroxymethyleneaporphine epimers gave separable mixtures of epimers. The epimeric ratios obtained in most reactions seem to be a result of steric factors directing the nucleophilic attack. The structure of the epimers was determined by a combination of X-ray crystallography (5 derivatives), NMR spectroscopy, and chemical correlation. Interesting and diverse pharmacological profiles of the derivatives were revealed through binding studies at serotonin 5-HT7 and 5-HT1A receptors as well as at dopamine D-2A receptors. Two derivatives appeared to be selective 5-HT7 receptor antagonists. It is evident from our results that the novel ring system [(R)-4] provides a useful complement to other scaffolds available to medicinal chemists involved in studies of GPC receptors.