7-{3-[4-((Z)-3-Dimethylamino-acryloyl)-2-ethyl-5-hydroxy-phenoxy]-propoxy}-8-propyl-chroman-2-carboxylic acid ethyl ester | 156005-67-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 7-{3-[4-((Z)-3-Dimethylamino-acryloyl)-2-ethyl-5-hydroxy-phenoxy]-propoxy}-8-propyl-chroman-2-carboxylic acid ethyl ester
• CAS: 156005-67-3
• 化学式: C₃₁H₄₁NO₇
• 分子量: 539.669
• InChiKey: NDRVQBOITRXLPM-UHFFFAOYSA-N

物化性质

• 沸点：
  674.9±55.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.27
• 重原子数：
  39.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  94.53
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  7-{3-[4-((Z)-3-Dimethylamino-acryloyl)-2-ethyl-5-hydroxy-phenoxy]-propoxy}-8-propyl-chroman-2-carboxylic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以94%的产率得到3,4-dihydro-8-propyl-7-<<3-<2-ethyl-5-hydroxy-4-<3-(dimethylamino)-1-oxo-2-propenyl>phenoxy>propyl>oxy>-2H-1-benzopyran-2-carboxylic acid
  参考文献：
  名称：

  Leukotriene B4 (LTB4) Receptor Antagonists: A Series of (Hydroxyphenyl)pyrazoles

  摘要：

  A series of (hydroxyphenyl)pyrazoles was designed by molecular modeling comparison with the LTB(4) structure and prepared for evaluation as LTB(4) receptor antagonists, culminating in 4-ethyl-5-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]-2-(1H-pyrazol-3-yl)phenyl (2). Using an assay for inhibition of specific [H-3]LTB(4) binding to human PMN, it was found that the pyrazole ring could be methylated at N(1) with little loss of activity while methylation at N(2) reduced activity significantly. The structure-activity relationship of the terminal acid group was investigated. Good activity was found with o- and m-phenylalkanoic acids, chromane carboxylic acid, and tetrazole groups. The best in vitro activity was realized with the pyrazole nitrogen unsubstituted and with a six-carbon chain linking the phenyl ether oxygen to the tetrazole group. Compound 2, having an IC50 of 6.4 +/- 0.8 nM in the binding assay, was selected for further preclinical evaluation.

  DOI：

  10.1021/jm00041a021
• 作为产物：
  描述：

  7-hydroxy-4-oxo-8-propyl-4H-1-benzopyran-2-carboxylic acid ethyl ester 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 25.0~155.0 ℃ 、358.53 kPa 条件下， 反应 64.5h， 生成 7-{3-[4-((Z)-3-Dimethylamino-acryloyl)-2-ethyl-5-hydroxy-phenoxy]-propoxy}-8-propyl-chroman-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Leukotriene B4 (LTB4) Receptor Antagonists: A Series of (Hydroxyphenyl)pyrazoles

  摘要：

  A series of (hydroxyphenyl)pyrazoles was designed by molecular modeling comparison with the LTB(4) structure and prepared for evaluation as LTB(4) receptor antagonists, culminating in 4-ethyl-5-[[6-methyl-6-(1H-tetrazol-5-yl)heptyl]oxy]-2-(1H-pyrazol-3-yl)phenyl (2). Using an assay for inhibition of specific [H-3]LTB(4) binding to human PMN, it was found that the pyrazole ring could be methylated at N(1) with little loss of activity while methylation at N(2) reduced activity significantly. The structure-activity relationship of the terminal acid group was investigated. Good activity was found with o- and m-phenylalkanoic acids, chromane carboxylic acid, and tetrazole groups. The best in vitro activity was realized with the pyrazole nitrogen unsubstituted and with a six-carbon chain linking the phenyl ether oxygen to the tetrazole group. Compound 2, having an IC50 of 6.4 +/- 0.8 nM in the binding assay, was selected for further preclinical evaluation.

  DOI：

  10.1021/jm00041a021