(+/-)-2-{1-[3-(4-benzyloxyphenoxy)propyl]-3-piperidyl}-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: (+/-)-2-{1-[3-(4-benzyloxyphenoxy)propyl]-3-piperidyl}-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 6,7-Dimethoxy-2-[1-[3-(4-phenylmethoxyphenoxy)propyl]piperidin-3-yl]-3,4-dihydroisoquinolin-1-one
• 化学式: C₃₂H₃₈N₂O₅
• 分子量: 530.664
• InChiKey: ROZKUPMORBJMBK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  60.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-苄氧基苯酚 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 19.0h， 生成 (+/-)-2-{1-[3-(4-benzyloxyphenoxy)propyl]-3-piperidyl}-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4- tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing I_f Channel Inhibitory Activity

  摘要：

  A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (+/-)-6,7-Dimethoxy-2-{1-[3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3,4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against I-f currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of I-f currents (IC50 = 0.32 muM) in guinea pig pacemaker cells.

  DOI：

  10.1021/jm0301742

文献信息

• Synthesis and Pharmacological Evaluation of 1-Oxo-2-(3-piperidyl)-1,2,3,4- tetrahydroisoquinolines and Related Analogues as a New Class of Specific Bradycardic Agents Possessing I_f Channel Inhibitory Activity
  作者：Hideki Kubota、Akio Kakefuda、Toshihiro Watanabe、Noe Ishii、Koichi Wada、Noriyuki Masuda、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1021/jm0301742

  日期：2003.10.1

  A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (+/-)-6,7-Dimethoxy-2-1-[3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3,4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against I-f currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of I-f currents (IC50 = 0.32 muM) in guinea pig pacemaker cells.