ethyl 1-methyl-4-oxo-1,4-dihydrocinnoline-3-carboxylate | 1500-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: ethyl 1-methyl-4-oxo-1,4-dihydrocinnoline-3-carboxylate
• 英文别名: 1,4-Dihydro-1-methyl-cinnolin-4-on-3-carbonsaeure-ethylester；1-methyl-4-oxo-1,4-dihydro-cinnoline-3-carboxylic acid ethyl ester；Ethyl 1-methyl-4-oxocinnoline-3-carboxylate
• CAS: 1500-44-3
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: RSCAUDBOTFTTLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 4-oxo-1,4-dihydrocinnoline-3-carboxylate 、 碘甲烷 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以66%的产率得到ethyl 1-methyl-4-oxo-1,4-dihydrocinnoline-3-carboxylate
  参考文献：
  名称：

  Cinnoline derivatives as human neutrophil elastase inhibitors

  摘要：

  Compounds that can effectively inhibit the proteolytic activity of human neutrophil elastase (HNE) represent promising therapeutics for treatment of inflammatory diseases. We present here the synthesis, structure-activity relationship analysis, and biological evaluation of a new series of HNE inhibitors with a cinnoline scaffold. These compounds exhibited HNE inhibitory activity but had lower potency compared to N-benzoylindazoles previously reported by us. On the other hand, they exhibited increased stability in aqueous solution. The most potent compound, 18a, had a good balance between HNE inhibitory activity (IC50 value = 56 nM) and chemical stability (t(1/2) = 114 min). Analysis of reaction kinetics revealed that these cinnoline derivatives were reversible competitive inhibitors of HNE. Furthermore, molecular docking studies of the active products into the HNE binding site revealed two types of HNE inhibitors: molecules with cinnolin-4(1H)-one scaffold, which were attacked by the HNE Ser195 hydroxyl group at the amido moiety, and cinnoline derivatives containing an ester function at C-4, which is the point of attack of Ser195.

  DOI：

  10.3109/14756366.2015.1057718