2-benzyl-6-(2-isopropyl-7-methoxypyrazolo[1,5-a]pyridin-4-yl)pyridazin-3(2H)-one | 909720-32-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-benzyl-6-(2-isopropyl-7-methoxypyrazolo[1,5-a]pyridin-4-yl)pyridazin-3(2H)-one
• 英文别名: 2-benzyl-6-(7-methoxy-2-propan-2-ylpyrazolo[1,5-a]pyridin-4-yl)pyridazin-3-one
• CAS: 909720-32-7
• 化学式: C₂₂H₂₂N₄O₂
• 分子量: 374.442
• InChiKey: KWDQBWJHNXTHPY-UHFFFAOYSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  59.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-benzyl-6-(2-isopropyl-7-methoxypyrazolo[1,5-a]pyridin-4-yl)pyridazin-3(2H)-one 在 锌 作用下， 以 溶剂黄146 为溶剂， 反应 0.17h， 以83%的产率得到2-benzyl-6-(2-isopropyl-7-methoxypyrazolo[1,5-a]pyridin-4-yl)-4,5-dihydropyridazin-3(2H)-one
  参考文献：
  名称：

  Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast

  摘要：

  Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structure-activity relationship exploration in the resulting 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazin-3(2H)-ones revealed that the pyridazinone lactam functionality is a critical determinant for PDE3-inhibitory activity, with the nitrogen preferably unsubstituted. PDE4 inhibition is strongly promoted by introduction of a hydrophobic substituent at the pyridazinone N(2) centre and a methoxy group at C-70 in the pyrazolopyridine. Migration of the pyridazinone ring connection from the pyrazolopyridine 30-centre to C-40 strongly enhances PDE4 inhibition. These studies establish a basis for development of potent PDE4-selective and dual PDE3/4-selective inhibitors derived from ibudilast. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.021
• 作为产物：
  描述：

  2-溴-6-甲氧基吡啶 在 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四(三苯基膦)钯 、 正丁基锂 、 silica gel 、 sodium hydride 、 sodium carbonate 、 potassium carbonate 、 溶剂黄146 、 二异丙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 2-benzyl-6-(2-isopropyl-7-methoxypyrazolo[1,5-a]pyridin-4-yl)pyridazin-3(2H)-one
  参考文献：
  名称：

  Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast

  摘要：

  Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structure-activity relationship exploration in the resulting 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazin-3(2H)-ones revealed that the pyridazinone lactam functionality is a critical determinant for PDE3-inhibitory activity, with the nitrogen preferably unsubstituted. PDE4 inhibition is strongly promoted by introduction of a hydrophobic substituent at the pyridazinone N(2) centre and a methoxy group at C-70 in the pyrazolopyridine. Migration of the pyridazinone ring connection from the pyrazolopyridine 30-centre to C-40 strongly enhances PDE4 inhibition. These studies establish a basis for development of potent PDE4-selective and dual PDE3/4-selective inhibitors derived from ibudilast. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.021

文献信息

• Phosphodiesterase inhibitors. Part 1: Synthesis and structure–activity relationships of pyrazolopyridine–pyridazinone PDE inhibitors developed from ibudilast
  作者：Robert W. Allcock、Haakon Blakli、Zhong Jiang、Karen A. Johnston、Keith M. Morgan、Georgina M. Rosair、Kazuhiko Iwase、Yasushi Kohno、David R. Adams

  DOI：10.1016/j.bmcl.2011.04.021

  日期：2011.6

  Ibudilast [1-(2-isopropylpyrazolo[1,5-a]pyridin-3-yl)-2-methylpropan-1-one] is a nonselective phosphodiesterase inhibitor used clinically to treat asthma. Efforts to selectively develop the PDE3- and PDE4-inhibitory activity of ibudilast led to replacement of the isopropyl ketone by a pyridazinone heterocycle. Structure-activity relationship exploration in the resulting 6-(pyrazolo[1,5-a]pyridin-3-yl)pyridazin-3(2H)-ones revealed that the pyridazinone lactam functionality is a critical determinant for PDE3-inhibitory activity, with the nitrogen preferably unsubstituted. PDE4 inhibition is strongly promoted by introduction of a hydrophobic substituent at the pyridazinone N(2) centre and a methoxy group at C-70 in the pyrazolopyridine. Migration of the pyridazinone ring connection from the pyrazolopyridine 30-centre to C-40 strongly enhances PDE4 inhibition. These studies establish a basis for development of potent PDE4-selective and dual PDE3/4-selective inhibitors derived from ibudilast. (C) 2011 Elsevier Ltd. All rights reserved.