5-hydroxy-4,7-dimethyl-3-(4-methylpiperazin-1-yl)-2H-chromen-2-one | 1209261-70-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 5-hydroxy-4,7-dimethyl-3-(4-methylpiperazin-1-yl)-2H-chromen-2-one
• 英文别名: 5-hydroxy-4,7-dimethyl-3-(4-methylpiperazin-1-yl)chromen-2-one
• CAS: 1209261-70-0
• 化学式: C₁₆H₂₀N₂O₃
• 分子量: 288.346
• InChiKey: YOTKRYVSTWYVEX-UHFFFAOYSA-N

物化性质

• 熔点：
  213-215 °C
• 沸点：
  478.7±45.0 °C(predicted)
• 密度：
  1.253±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  53
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二羟基甲苯 、 Ethyl 2-(4-methylpiperazin-1-yl)-3-oxobutanoate 在 三氟化硼乙醚 作用下， 以 乙醇 为溶剂， 生成 5-hydroxy-4,7-dimethyl-3-(4-methylpiperazin-1-yl)-2H-chromen-2-one
  参考文献：
  名称：

  Discovery and Optimization of Novel 3-Piperazinylcoumarin Antagonist of Chemokine-like Factor 1 with Oral Antiasthma Activity in Mice

  摘要：

  Chemokine-like factor 1 (CKLF1) is a novel functional cytokine that acts through receptor CC chemokine receptor 4 (CCR4). Activation of CCR4 by CKLF1 plays an important role in diseases such as asthma and multiple Sclerosis. This article describes a cell-based screening assay Using an FITC-labeled CCR4 agonist (CKLF1-C27), a CKLF1 peptide fragment. Screening of our in-stock small-molecule library identified a 3-piperazinylcoumarin analogue 1 (IC50 = 4.36 x 10(-6) M) that led to the discovery of orally active compound 41 (IC50 = 2.12 x 10(-8) M) through systematic optimization. Compound 41 blocked the calcium mobilization and chemotaxis induced by CKLF1-C27 and reduced the asthmatic pathologic changes in lung tissue of human CKLF1-transfected mice. Further studies indicated that compound 41 ameliorated pathological changes via inhibition of the NF-kappa B signal pathway.

  DOI：

  10.1021/jm901652p

文献信息

• Discovery and Optimization of Novel 3-Piperazinylcoumarin Antagonist of Chemokine-like Factor 1 with Oral Antiasthma Activity in Mice
  作者：Gang Li、Dongmei Wang、Mingna Sun、Guangyan Li、Jinfeng Hu、Yun Zhang、Yuhe Yuan、Haijie Ji、Naihong Chen、Gang Liu

  DOI：10.1021/jm901652p

  日期：2010.2.25

  Chemokine-like factor 1 (CKLF1) is a novel functional cytokine that acts through receptor CC chemokine receptor 4 (CCR4). Activation of CCR4 by CKLF1 plays an important role in diseases such as asthma and multiple Sclerosis. This article describes a cell-based screening assay Using an FITC-labeled CCR4 agonist (CKLF1-C27), a CKLF1 peptide fragment. Screening of our in-stock small-molecule library identified a 3-piperazinylcoumarin analogue 1 (IC50 = 4.36 x 10(-6) M) that led to the discovery of orally active compound 41 (IC50 = 2.12 x 10(-8) M) through systematic optimization. Compound 41 blocked the calcium mobilization and chemotaxis induced by CKLF1-C27 and reduced the asthmatic pathologic changes in lung tissue of human CKLF1-transfected mice. Further studies indicated that compound 41 ameliorated pathological changes via inhibition of the NF-kappa B signal pathway.