isopropyl 6-ethyl-6,7-dihydro-3-methyl-2-(3-nitrophenyl)-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylate | 1228804-87-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: isopropyl 6-ethyl-6,7-dihydro-3-methyl-2-(3-nitrophenyl)-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylate
• 英文别名: Propan-2-yl 6-ethyl-3-methyl-2-(3-nitrophenyl)-7-oxopyrazolo[3,4-d]pyridazine-4-carboxylate
• CAS: 1228804-87-2
• 化学式: C₁₈H₁₉N₅O₅
• 分子量: 385.379
• InChiKey: UCBYHZVUSLUYFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  123
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-ethyl-6,7-dihydro-3-methyl-2-(3-nitrophenyl)-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylic acid 、 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， 以96%的产率得到isopropyl 6-ethyl-6,7-dihydro-3-methyl-2-(3-nitrophenyl)-7-oxo-2H-pyrazolo[3,4-d]pyridazine-4-carboxylate
  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

文献信息

• Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity
  作者：Pierfrancesco Biagini、Claudio Biancalani、Alessia Graziano、Nicoletta Cesari、Maria Paola Giovannoni、Agostino Cilibrizzi、Vittorio Dal Piaz、Claudia Vergelli、Letizia Crocetti、Maurizio Delcanale、Elisabetta Armani、Andrea Rizzi、Paola Puccini、Paola Maria Gallo、Daniele Spinabelli、Paola Caruso

  DOI：10.1016/j.bmc.2010.03.066

  日期：2010.5

  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.