(+/-)-3-amino-1-[3-(3,4-methylenedioxyphenoxy)propyl]-piperidine | 619329-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 英文名称: (+/-)-3-amino-1-[3-(3,4-methylenedioxyphenoxy)propyl]-piperidine
• 英文别名: 1-[3-(1,3-Benzodioxol-5-yloxy)propyl]piperidin-3-amine
• CAS: 619329-87-2
• 化学式: C₁₅H₂₂N₂O₃
• 分子量: 278.351
• InChiKey: DRANRBOOGBWHOT-UHFFFAOYSA-N

物化性质

• 沸点：
  416.9±45.0 °C(Predicted)
• 密度：
  1.165±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  57
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-3-amino-1-[3-(3,4-methylenedioxyphenoxy)propyl]-piperidine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 27.0h， 生成 (+/-)-6,7-dimethoxy-3-{1-[3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-4-oxo-3,4-dihydroquinazoline
  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-[3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidone 在 吡啶 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 19.0h， 生成 (+/-)-3-amino-1-[3-(3,4-methylenedioxyphenoxy)propyl]-piperidine
  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.