(R)-(-)-10-O-(1-phenyltetrazol-5-yl)-11-methoxyaporphine | 40169-98-0

• 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)-(-)-10-O-(1-phenyltetrazol-5-yl)-11-methoxyaporphine
• 英文别名: 11-methoxy-10-O-(1-phenyltetrazol-5-yl)apomorphine；(6aR)-11-methoxy-6-methyl-10-(1-phenyltetrazol-5-yl)oxy-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• CAS: 40169-98-0
• 化学式: C₂₅H₂₃N₅O₂
• 分子量: 425.49
• InChiKey: IFZHSPYOIJYFBW-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.22
• 重原子数：
  32.0
• 可旋转键数：
  4.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  65.3
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (R)-(-)-10-O-(1-phenyltetrazol-5-yl)-11-methoxyaporphine 以56%的产率得到
  参考文献：
  名称：

  CANNON, JOSEPH G.;MOHAN, PREM;BOJARSKI, JACEK;LONG, JOHN PAUL;BHATNAGAR, +, J. MED. CHEM., 31,(1988) N 2, 313-318

  摘要：

  DOI：
• 作为产物：
  描述：

  吗啡 在 甲烷磺酸 、 potassium carbonate 作用下， 以 乙醚 、 丙酮 为溶剂， 反应 25.0h， 生成 (R)-(-)-10-O-(1-phenyltetrazol-5-yl)-11-methoxyaporphine
  参考文献：
  名称：

  Aporphines. 42. Synthesis of (R)-(-)-11-hydroxyaporphines

  摘要：

  DOI：

  10.1021/jo00143a050

文献信息

• 5-HT1A-Receptor antagonism: N-alkyl derivatives of (R)-(-)-8,11-dimethoxynoraporphine
  作者：Joseph G. Cannon、Henry Jackson、John Paul Long、Paul Leonard、Ranbir K. Bhatnagar

  DOI：10.1021/jm00128a044

  日期：1989.8

  Prompted by previous findings that a p-dimethoxy substitution pattern on an aromatic ring permits retention of dopaminergic agonist effects in certain ring systems, catechol derivatives of which are potent dopaminergic agonists, an 8,11-dimethoxy substitution pattern was introduced into the aporphine ring in place of the 10,11-dihydroxy moiety in apomorphine. Acid-catalyzed rearrangement of an appropriate

  以前的发现提示，芳环上的对二甲氧基取代模式可在某些环系统中保留多巴胺能激动剂效应，其中邻苯二酚衍生物是有效的多巴胺能激动剂，将8,11-二甲氧基取代模式引入了Aph环中。在阿扑吗啡中的10,11-二羟基部分的位置。适当的吗啡衍生物的酸催化重排为阿福啡环系统提供了6a不对称中心立体化学完整性的保留。通过催化氢解其苯基四唑基醚除去位置10处的羟基。用三氟乙酰基亚硫酸氢盐在8位以高收率碘化所得的11-羟基阿扑吗啡的甲基醚。这是合成碘化的海豚碱衍生物的第一个说明。通过与甲醇钠和碘化亚铜反应，将8-碘取代基替换为甲氧基。N-甲基靶标化合物7或Nn-丙基衍生物8均未显示出多巴胺能或血清素能激动作用。但是，有7种药物具有受体结合特性和其他药理特性，表明它可能是5-HT1A受体拮抗剂。
• 3-O-(1-Phenyltetrazol-5-yl)morphine in the Acid-catalyzed Morphine-Apomorphine Rrearrangement: Formation of a Side Product Due to 1-Phenyltetrazole Group Migration
  作者：Prem Mohan、Joseph G. Cannon

  DOI：10.3987/com-88-4589

  日期：——
• (R)-(-)-10-Methyl-11-hydroxyaporphine: a highly selective serotonergic agonist
  作者：Joseph G. Cannon、Prem Mohan、Jacek Bojarski、John Paul Long、Ranbir K. Bhatnagar、Paul A. Leonard、Jan R. Flynn、Tapan K. Chatterjee

  DOI：10.1021/jm00397a007

  日期：1988.2

  Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.
• CANNON, JOSEPH G.;JACKSON, HENRY;LONG, JOHN PAUL;BHATNAGAR, RANBIR K., J. MED. CHEM., 32,(1989) N, C. 1959-1962
  作者：CANNON, JOSEPH G.、JACKSON, HENRY、LONG, JOHN PAUL、BHATNAGAR, RANBIR K.

  DOI：——

  日期：——