cis-1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-<(3,4-dichloro)phenyl>-1,2,3,4-tetrahydroisoquinolin-3-(2H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: cis-1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-<(3,4-dichloro)phenyl>-1,2,3,4-tetrahydroisoquinolin-3-(2H)-one
• 英文别名: (1S,4S)-4-(3,4-dichlorophenyl)-2-methyl-1-(pyrrolidin-1-ylmethyl)-1,4-dihydroisoquinolin-3-one
• 化学式: C₂₁H₂₂Cl₂N₂O
• 分子量: 389.324
• InChiKey: QNJJRRASOXFHQC-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-氨基-2-苯基乙酸 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 硫酸 、 N,N'-羰基二咪唑 作用下， 以 乙醚 为溶剂， 反应 29.5h， 生成 cis-1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-<(3,4-dichloro)phenyl>-1,2,3,4-tetrahydroisoquinolin-3-(2H)-one
  参考文献：
  名称：

  Synthesis and κ binding affinity of 1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-[(3,4-dichloro)phenyl]-1,2,3,4 tetrahydroisoquinolin-3(2H)-ones

  摘要：

  Diastereomeric forms of 1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-[(3,4-dichloro)phenyl]-1,2,3,4-tetrahydroisoquinoline-3(2h)-ones 3a and its chloro analog 3c were synthesized. Compounds 3a,c are related to the kappa-selective opiate ICI 199441 1 by linking the benzylic CH2 to the ortho position of the phenyl in 1. Compared with morphine, these compounds had lost in kappa and mu affinities; only cis-3a showed a modest kappa affinity. 1-Pyrrolidin-1-ylmethyl-N-[2-(3,4-dichlorphenyl)acetyl]-1,2,3,4-tetrahydroisoquinoline 2, which is also a cyclic congener of 1, was reported to display high kappa and mu affinity, and so a conformational study was undertaken on 1, 2 and 3a. This showed that, while active 2 extensively superposed on 1, 3a assumes another geometry which does not allow a fit with the pharmacophoric moieties of 1 and 2.

  DOI：

  10.1016/0223-5234(96)88263-8

文献信息

• Synthesis and κ binding affinity of 1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-[(3,4-dichloro)phenyl]-1,2,3,4 tetrahydroisoquinolin-3(2H)-ones
  作者：GA Pinna、E Gavini、G Cignarella、S Scolastico、P Fadda

  DOI：10.1016/0223-5234(96)88263-8

  日期：1995.1

  Diastereomeric forms of 1-(pyrrolidin-1-ylmethyl)-2-(N-methyl)-4-[(3,4-dichloro)phenyl]-1,2,3,4-tetrahydroisoquinoline-3(2h)-ones 3a and its chloro analog 3c were synthesized. Compounds 3a,c are related to the kappa-selective opiate ICI 199441 1 by linking the benzylic CH2 to the ortho position of the phenyl in 1. Compared with morphine, these compounds had lost in kappa and mu affinities; only cis-3a showed a modest kappa affinity. 1-Pyrrolidin-1-ylmethyl-N-[2-(3,4-dichlorphenyl)acetyl]-1,2,3,4-tetrahydroisoquinoline 2, which is also a cyclic congener of 1, was reported to display high kappa and mu affinity, and so a conformational study was undertaken on 1, 2 and 3a. This showed that, while active 2 extensively superposed on 1, 3a assumes another geometry which does not allow a fit with the pharmacophoric moieties of 1 and 2.