(+/-)-2-(1-benzyl-3-piperidyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline | 204979-29-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (+/-)-2-(1-benzyl-3-piperidyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline
• 英文别名: (+/-)-2-(1-benzyl-3-piperidyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydtoisoquinoline；2-(1-Benzylpiperidin-3-yl)-6,7-dimethoxy-3,4-dihydroisoquinolin-1-one
• CAS: 204979-29-3
• 化学式: C₂₃H₂₈N₂O₃
• 分子量: 380.487
• InChiKey: HQDAOSWIBCWVFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-2-(1-benzyl-3-piperidyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、392.24 kPa 条件下， 反应 24.0h， 以79%的产率得到(+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroiaoquinoline
  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
• 作为产物：
  描述：

  1-苄基-3-哌啶酮盐酸盐 在 4-二甲氨基吡啶 、 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 74.0h， 生成 (+/-)-2-(1-benzyl-3-piperidyl)-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  AN EFFICIENT SYNTHESIS OF (±)-6,7-DIMETHOXY-1-OXO-2-(3-PIPERIDYL)-1,2,3,4-TETRAHYDROISOQUINOLINE

  摘要：

  The synthesis of (+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinoline (1) via the cyclization of dimethyl-acetal (3) under acidic condition is described.

  DOI：

  10.1081/scc-100000530

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.
• AN EFFICIENT SYNTHESIS OF (±)-6,7-DIMETHOXY-1-OXO-2-(3-PIPERIDYL)-1,2,3,4-TETRAHYDROISOQUINOLINE
  作者：Akio Kakefuda、Toshihiro Watanabe、Takumi Takahashi、Shuichi Sakamoto、Shin-Ichi Tsukamoto

  DOI：10.1081/scc-100000530

  日期：2001.1

  The synthesis of (+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinoline (1) via the cyclization of dimethyl-acetal (3) under acidic condition is described.