(+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroiaoquinoline | 204979-30-6

• 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: (+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroiaoquinoline
• 英文别名: (+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinoline；6,7-Dimethoxy-2-piperidin-3-yl-3,4-dihydroisoquinolin-1-one
• CAS: 204979-30-6
• 化学式: C₁₆H₂₂N₂O₃
• 分子量: 290.362
• InChiKey: IQBHNBYOZVMOLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(3-溴丙氧基)-4-氟苯 、 (+/-)-6,7-dimethoxy-1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroiaoquinoline 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 12.0h， 生成 (+/-)-6,7-dimethoxy-2-{1-[3-(4-fluorophenoxy)propyl]-3-piperidyl}-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
• 作为产物：
  描述：

  1-benzyl-3-[(3,4-dimethoxyphenethyl)amino]piperidine 在 盐酸 、 4-二甲氨基吡啶 、 trifluoromethanesulfonic acid anhydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0 ℃ 、392.24 kPa 条件下， 反应 97.0h， 生成 (+/-)-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

文献信息

• イソキノリノン誘導体又はその塩
  申请人：山之内製薬株式会社

  公开号：JP2000302778A

  公开（公告）日：2000-10-31

  (57)【要約】\n【課題】 If電流阻害作用を有し、心拍数低下剤として特に狭心症（胸部狭心症）や心筋梗塞等の虚血性心疾患、うっ血性心不全及び不整脈（上室性不整脈等）等の循環器系疾患の予防又は治療に有用な化合物の創製。\n【解決手段】下記一般式（Ｉ）で示されるイソキノリノン誘導体又はその塩。\n【化１】\n(上記式中の記号は、それぞれ以下の意味を有する。Ｒ1及びＲ2：同一又は異なって水素原子、-低級アルキル、-Ｏ-低級アルキル、又はＲ1とＲ2は一体となって-Ｏ-低級アルキレン-Ｏ-、\nＡ：低級アルキレン、\nＢ：-Ｃ（＝Ｏ）-ＮＨ-又は-ＮＨ-Ｃ（＝Ｏ）-\nＤ：置換されていてもよい炭化水素環又は置換されていてもよくベンゼン環で縮合されていてもよいヘテロ環）

  (57) Јn[摘要] Јn[问题] 创造具有 If 电流抑制作用并可作为降低心率药物的化合物，特别是用于预防或治疗心血管疾病，如心绞痛（胸绞痛）、心肌梗塞和其他缺血性心脏病、充血性心力衰竭和心律失常（如室上性心律失常）。\解法】一种异喹啉酮衍生物或其盐，通式（I）如下。\Јn[Ј1] Јn（上式中的符号分别具有以下含义：R1 和 R2：氢原子、-低级烷基、-O-低级烷基，或 R1 和 R2 与-O-低级亚烷基-O-一起，ЈnA：低级亚烷基，ЈnB：-C(=O)-NH- 或 -NH-。C(=O)-ЈnD：可被取代的烃环或可被取代或与苯环融合的杂环)
• 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.
• 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.