7-Pyridin-3-yl-2-[1-(2,3,6-trimethoxy-4,5-dimethyl-phenyl)-meth-(E)-ylidene]-heptanoic acid ethyl ester | 144562-69-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 7-Pyridin-3-yl-2-[1-(2,3,6-trimethoxy-4,5-dimethyl-phenyl)-meth-(E)-ylidene]-heptanoic acid ethyl ester
• 英文别名: ethyl (2E)-7-pyridin-3-yl-2-[(2,3,6-trimethoxy-4,5-dimethylphenyl)methylidene]heptanoate
• CAS: 144562-69-6
• 化学式: C₂₆H₃₅NO₅
• 分子量: 441.568
• InChiKey: AVDSAXFSXOFTTC-LTGZKZEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  32
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-Pyridin-3-yl-2-[1-(2,3,6-trimethoxy-4,5-dimethyl-phenyl)-meth-(E)-ylidene]-heptanoic acid ethyl ester 在 sodium hydroxide 、 sodium disulfite 、 ammonium cerium(IV) nitrate 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 1.5h， 生成 (E)-3-(2,5-dihydroxy-6-methoxy-3,4-dimethylphenyl)-2-[5-(3-pyridyl)pentyl]-2-propenoic acid
  参考文献：
  名称：

  Structure−Activity Relationships of (E)-3-(1,4-Benzoquinonyl)-2-[(3-pyridyl)- alkyl]-2-propenoic Acid Derivatives That Inhibit Both 5-Lipoxygenase and Thromboxane A₂ Synthetase

  摘要：

  As part of our research for the development of novel antiinflammatory drug candidates, we have designed and synthesized a series of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A(2) synthetase. In order to increase the absorption after oral administration, we introduced a carboxylic acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4-benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory activities against the production of leukotriene (LT) Bq and TXA(2) while not significantly inhibiting that of prostaglandin E(2) by glycogen-induced peritoneal cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl group influenced the inhibition of LTB(4) and TXB(2) production. An increase of lipophilicity by introducing a more lipophilic alkoxy group did not markedly increase the inhibitory activity on LTB(4) production. The position of an alkoxy group on the 1,4-benzoquinone skeleton played an important role in TXA(2) synthetase inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and proper length of methylene side chain, together with a polar substituent (carboxylic acid), showed good inhibition of both 5-LO and TXA(2) synthetase and possess a variety of pharmacologically beneficial effects.

  DOI：

  10.1021/jm950725r
• 作为产物：
  描述：

  5-吡啶-3-基-戊-1-醇 在 sodium hydride 、 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 7-Pyridin-3-yl-2-[1-(2,3,6-trimethoxy-4,5-dimethyl-phenyl)-meth-(E)-ylidene]-heptanoic acid ethyl ester
  参考文献：
  名称：

  Structure−Activity Relationships of (E)-3-(1,4-Benzoquinonyl)-2-[(3-pyridyl)- alkyl]-2-propenoic Acid Derivatives That Inhibit Both 5-Lipoxygenase and Thromboxane A₂ Synthetase

  摘要：

  As part of our research for the development of novel antiinflammatory drug candidates, we have designed and synthesized a series of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A(2) synthetase. In order to increase the absorption after oral administration, we introduced a carboxylic acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4-benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory activities against the production of leukotriene (LT) Bq and TXA(2) while not significantly inhibiting that of prostaglandin E(2) by glycogen-induced peritoneal cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl group influenced the inhibition of LTB(4) and TXB(2) production. An increase of lipophilicity by introducing a more lipophilic alkoxy group did not markedly increase the inhibitory activity on LTB(4) production. The position of an alkoxy group on the 1,4-benzoquinone skeleton played an important role in TXA(2) synthetase inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and proper length of methylene side chain, together with a polar substituent (carboxylic acid), showed good inhibition of both 5-LO and TXA(2) synthetase and possess a variety of pharmacologically beneficial effects.

  DOI：

  10.1021/jm950725r