2-(2,6-dichlorophenyl)-6-ethyl-6,7-dihydro-3-methyl-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid | 1228804-74-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2,6-dichlorophenyl)-6-ethyl-6,7-dihydro-3-methyl-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid
• CAS: 1228804-74-7
• 化学式: C₁₅H₁₂Cl₂N₄O₃
• 分子量: 367.191
• InChiKey: YXVSULYSKFMBHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.92
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  90.01
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2-(2,6-dichlorophenyl)-6-ethyl-6,7-dihydro-3-methyl-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 生成
  参考文献：
  名称：

  Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity

  摘要：

  A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-alpha release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.066
• 作为产物：
  描述：

  ethyl 2-(2,6-dichlorophenyl)-6-ethyl-6,7-dihydro-3-methyl-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以72%的产率得到2-(2,6-dichlorophenyl)-6-ethyl-6,7-dihydro-3-methyl-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid
  参考文献：
  名称：

  Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity

  摘要：

  A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-alpha release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.066