(E)-3-(2,4,5-Trimethoxy-3,6-dimethylphenyl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid | 144562-60-7

• 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: (E)-3-(2,4,5-Trimethoxy-3,6-dimethylphenyl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid
• 英文别名: (E)-3-(2,4,5-Trimethoxy-3,6-dimethylphenyl)-2-[5-(3-pyridyl)pentyl]-2-propenoic acid；(2E)-7-pyridin-3-yl-2-[(2,4,5-trimethoxy-3,6-dimethylphenyl)methylidene]heptanoic acid
• CAS: 144562-60-7
• 化学式: C₂₄H₃₁NO₅
• 分子量: 413.514
• InChiKey: PCHIZMVMBGWPCO-XMHGGMMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(2,4,5-Trimethoxy-3,6-dimethylphenyl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid 在 ammonium cerium(IV) nitrate 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 以74%的产率得到(E)-3-(2-methoxy-3,6-dimethyl-1,4-benzoquinon-5-yl)-2-[5-(pyridin-3-yl)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：

  2,5-dimethoxy-3,6-dimethylphenol 在 sodium hydroxide 、 四氯化钛 、 sodium hydride 作用下， 以 乙醇 、 水 为溶剂， 反应 8.0h， 生成 (E)-3-(2,4,5-Trimethoxy-3,6-dimethylphenyl)-2-[5-(pyridin-3-yl)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

文献信息

• Quinone derivatives
  申请人：Eisai Co., Ltd.

  公开号：US05329010A1

  公开（公告）日：1994-07-12

  The present invention is a quinone derivative which exhibits excellent therapeutic activity represented by the general formula (I) or a pharmacologically acceptable salt thereof: ##STR1## wherein A stands for a group represented by the formula: ##STR2## (wherein R.sup.3, R.sup.4 and R.sup.5 is the same or different from each other and each stand for a hydrogen atom, a hydroxyl group, a lower alkyl group, a lower alkoxy group, an alkoxyalkyl group, an alkoxyalkoxy group, a cycloalkylalkoxy group, a thiol group or a thioalkyl group, with the proviso that R.sup.3 and R.sup.4 are each a lower alkoxy group R.sup.1 stands for a heteroarylalkyl group; and B stands for a carboxyl group or a protected carboxyl group.

  本发明涉及一种喹酮衍生物，其具有优异的治疗活性，其通式（I）或其药理学上可接受的盐表示为：##STR1##其中A代表由以下公式表示的基团：##STR2##（其中R.sup.3，R.sup.4和R.sup.5相同或不同，分别代表氢原子，羟基，低碳基，低烷氧基，烷氧基烷基，烷氧基烷氧基，环烷烷氧基，硫醇基或硫代烷基，但R.sup.3和R.sup.4分别为低烷氧基；R.sup.1代表杂环烷基烷基；B代表羧基或保护羧基。
• US5329010A
  申请人：——

  公开号：US5329010A

  公开（公告）日：1994-07-12
• Structure−Activity Relationships of (<i>E</i>)<i>-</i>3-(1,4-Benzoquinonyl)-2-[(3-pyridyl)- alkyl]-2-propenoic Acid Derivatives That Inhibit Both 5-Lipoxygenase and Thromboxane A₂ Synthetase
  作者：Shigeki Hibi、Yasushi Okamoto、Katsuya Tagami、Hirotoshi Numata、Naoki Kobayashi、Masanobu Shinoda、Tetsuya Kawahara、Koukichi Harada、Kaname Miyamoto、Isao Yamatsu

  DOI：10.1021/jm950725r

  日期：1996.1.1

  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.