6-benzyl-4-bromomethyl-3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one | 910316-49-3

• 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: 6-benzyl-4-bromomethyl-3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one
• 英文别名: 6-Benzyl-4-(bromomethyl)-3-methyl-[1,2]oxazolo[3,4-d]pyridazin-7-one
• CAS: 910316-49-3
• 化学式: C₁₄H₁₂BrN₃O₂
• 分子量: 334.172
• InChiKey: NFESVYSXXRUQFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  58.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-benzyl-4-bromomethyl-3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one 在 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 6-benzyl-4-[(dimethylamino)methyl]-3-styrylisoxazolo[3,4-d]pyridazin-7(6H)-one
  参考文献：
  名称：

  Novel Pyrazolopyrimidopyridazinones with Potent and Selective Phosphodiesterase 5 (PDE5) Inhibitory Activity as Potential Agents for Treatment of Erectile Dysfunction

  摘要：

  Pyrazolo[1', 5': 1,6] pyrimido[4,5-d] pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 = 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.

  DOI：

  10.1021/jm060265+
• 作为产物：
  描述：

  1-ethoxy-2,4-pentanedione 在 氢溴酸 、 sodium ethanolate 、 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 6-benzyl-4-bromomethyl-3-methylisoxazolo[3,4-d]pyridazin-7(6H)-one
  参考文献：
  名称：

  Novel Pyrazolopyrimidopyridazinones with Potent and Selective Phosphodiesterase 5 (PDE5) Inhibitory Activity as Potential Agents for Treatment of Erectile Dysfunction

  摘要：

  Pyrazolo[1', 5': 1,6] pyrimido[4,5-d] pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 = 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.

  DOI：

  10.1021/jm060265+

文献信息

• Novel Pyrazolopyrimidopyridazinones with Potent and Selective Phosphodiesterase 5 (PDE5) Inhibitory Activity as Potential Agents for Treatment of Erectile Dysfunction
  作者：Maria Paola Giovannoni、Claudia Vergelli、Claudio Biancalani、Nicoletta Cesari、Alessia Graziano、Pierfrancesco Biagini、Jordi Gracia、Amadeu Gavaldà、Vittorio Dal Piaz

  DOI：10.1021/jm060265+

  日期：2006.8.1

  Pyrazolo[1', 5': 1,6] pyrimido[4,5-d] pyridazin-4(3H)-ones and their analogues, potentially useful for the treatment of erectile dysfunction, were synthesized and evaluated as inhibitors of phosphodiesterase 5 (PDE5). Several compounds showed IC50 values in the low nanomolar range, and in particular, compound 5r, displaying high potency toward PDE5 (IC50 = 8.3 nM) and high selectivity versus PDE6 (240-fold) appeared to be a very promising new lead both in comparison with the potent but not selective sildenafil and in comparison with some analogues previously reported by us. SAR studies in this triheterocyclic scaffold led us to conclude that the best arranged groups are a methyl in position 1, a benzyl in position 3, a phenyl in position 9, and a linear four-carbon chain in position 6.