6-benzyl-3,4-dimethylisoxazolo[3,4-d]pyridazin-7(6H)-one | 910315-64-9

• 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-3,4-dimethylisoxazolo[3,4-d]pyridazin-7(6H)-one
• 英文别名: 6-Benzyl-3,4-dimethyl-[1,2]oxazolo[3,4-d]pyridazin-7-one
• CAS: 910315-64-9
• 化学式: C₁₄H₁₃N₃O₂
• 分子量: 255.276
• InChiKey: LZLAAQIIZBMDHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  2
• 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-3,4-dimethylisoxazolo[3,4-d]pyridazin-7(6H)-one 、 3-糠醛 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以98%的产率得到6-benzyl-3-[2-(furan-3-yl)ethenyl]-4-methyl-[1,2]oxazolo[3,4-d]pyridazin-7-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：

  3,4-二甲基-6H-异噁唑并[3,4-d]哒嗪-7-酮 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-benzyl-3,4-dimethylisoxazolo[3,4-d]pyridazin-7(6H)-one
  参考文献：
  名称：

  Pyrazolo[1′,5′:1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as selective human A1 adenosine receptor ligands

  摘要：

  A series of pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones was synthesized and tested in radio-ligand binding assays to determine their affinities for the human adenosine A(1), A(2A), A(2B) and A(3) receptors. Results indicated that this scaffold is appropriate for adenosine receptor subtype A1 ligands and that the best arranged groups around this scaffold are 3- and 4-pyridinyl at position 1, benzyl at position 3, hydrogen at position 6 and 3- thienyl or phenyl at position 9. The most interesting compounds showed K-i for A1 in the nanomolar range and an appreciable selectivity for other receptor subtypes. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.043

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.
• Pyrazolo[1′,5′:1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as selective human A1 adenosine receptor ligands
  作者：Maria Paola Giovannoni、Claudia Vergelli、Agostino Cilibrizzi、Letizia Crocetti、Claudio Biancalani、Alessia Graziano、Vittorio Dal Piaz、Maria Isabel Loza、Maria Isabel Cadavid、José Luis Díaz

  DOI：10.1016/j.bmc.2010.09.043

  日期：2010.11.15

  A series of pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones was synthesized and tested in radio-ligand binding assays to determine their affinities for the human adenosine A(1), A(2A), A(2B) and A(3) receptors. Results indicated that this scaffold is appropriate for adenosine receptor subtype A1 ligands and that the best arranged groups around this scaffold are 3- and 4-pyridinyl at position 1, benzyl at position 3, hydrogen at position 6 and 3- thienyl or phenyl at position 9. The most interesting compounds showed K-i for A1 in the nanomolar range and an appreciable selectivity for other receptor subtypes. (C) 2010 Elsevier Ltd. All rights reserved.