methyl 3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzoate | 1207862-96-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzoate
• CAS: 1207862-96-1
• 化学式: C₁₉H₁₇NO₄
• 分子量: 323.348
• InChiKey: RUIDEYMKNNYUDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  68.39
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl 3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzoate 在 盐酸 作用下， 以 水 为溶剂， 反应 2.0h， 以94%的产率得到3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methyl benzoic acid
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors

  摘要：

  Selective PDE3 (phosphodiesterase 3) inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this work ten new synthetic compounds (3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzamide analogs: 4a-j) were designed, synthesized and tested for the inhibitory activity against human PDE3A and PDE3B. The strategy of the design was based on the structure of vesnarinone (a selective PDE3 inhibitor) and its docking analysis results. The synthetic compounds showed better PDE3 inhibitory activity in comparison with vesnarinone. Using docking analysis, a common binding model of each compound toward PDE3 was suggested. In the next step the potential cardiotonic activity of the best PDE3A inhibitors (4b, IC(50) = 0.43 +/- 0.04 mu M) was evaluated by using the spontaneously beating atria model. In the experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of the synthetic compound were assessed. That was carried out in comparison with vesnarinone. The best pharmacological profile was obtained for the compound 4b, which displayed selectivity for increasing the force of contraction (46 +/- 3% change over the control) rather than the frequency rate (16 +/- 4% change over the control) at 100 mu M. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.044
• 作为产物：
  描述：

  2,6-二羟基-4-甲基喹啉 、 3-(溴甲基)苯甲酸甲酯 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 异丙醇 为溶剂， 以74%的产率得到methyl 3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzoate
  参考文献：
  名称：

  Design, synthesis and biological evaluation of 6-(benzyloxy)-4-methylquinolin-2(1H)-one derivatives as PDE3 inhibitors

  摘要：

  Selective PDE3 (phosphodiesterase 3) inhibitors improve cardiac contractility and may be used in congestive heart failure. However, their proarrhythmic potential is the most important side effect. In this work ten new synthetic compounds (3-[(4-methyl-2-oxo-1,2-dihydro-6-quinolinyl)oxy]methylbenzamide analogs: 4a-j) were designed, synthesized and tested for the inhibitory activity against human PDE3A and PDE3B. The strategy of the design was based on the structure of vesnarinone (a selective PDE3 inhibitor) and its docking analysis results. The synthetic compounds showed better PDE3 inhibitory activity in comparison with vesnarinone. Using docking analysis, a common binding model of each compound toward PDE3 was suggested. In the next step the potential cardiotonic activity of the best PDE3A inhibitors (4b, IC(50) = 0.43 +/- 0.04 mu M) was evaluated by using the spontaneously beating atria model. In the experiment, atrium of reserpine-treated rat was isolated and the contractile and chronotropic effects of the synthetic compound were assessed. That was carried out in comparison with vesnarinone. The best pharmacological profile was obtained for the compound 4b, which displayed selectivity for increasing the force of contraction (46 +/- 3% change over the control) rather than the frequency rate (16 +/- 4% change over the control) at 100 mu M. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.11.044