(E)-3-(2-Methoxy-3,5-dimethyl-1,4-benzoquinon-6-yl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid | 144563-00-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (E)-3-(2-Methoxy-3,5-dimethyl-1,4-benzoquinon-6-yl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid
• 英文别名: (E)-3-(2-Methoxy-3,5-dimethyl-1,4-benzoquinon-6-yl)-2-[5-(3-pyridyl)pentyl]-2-propenoic acid；(2E)-2-[(5-methoxy-2,4-dimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)methylidene]-7-pyridin-3-ylheptanoic acid
• CAS: 144563-00-8
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: RUYJLTZVAHNUKM-SFQUDFHCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  93.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-(2-Methoxy-3,5-dimethyl-1,4-benzoquinon-6-yl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid 在 sodium disulfite 作用下， 以 水 、 乙酸乙酯 为溶剂， 以79%的产率得到(E)-3-(2,5-dihydroxy-3-methoxy-4,6-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：

  3-(5-Chloro-pentyl)-pyridine 在 sodium hydroxide 、 ammonium cerium(IV) nitrate 、 sodium hydride 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 15.5h， 生成 (E)-3-(2-Methoxy-3,5-dimethyl-1,4-benzoquinon-6-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

文献信息

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

  公开号：EP0503426A1

  公开（公告）日：1992-09-16

  The object of the present invention is to provide a quinone derivative exhibiting an excellent activity as a drug. The present invention provides a quinone derivative represented by the general formula (I) or a pharmacologically acceptable salt thereof:    wherein A stands for a group represented by the formula:    (wherein R³, R⁴ and R⁵ 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 a case wherein R³ and R⁴ are each a lower alkoxy group simultaneously is excepted) or a group represented by the formula:    (wherein R³, R⁴ and R⁵ 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 a case wherein R³ and R⁴ are each a lower alkoxy group simultaneously is excepted; X and Y is the same or different from each other and each stand for a hydroxyl group or a protected hydroxyl group); R¹ stands for a heteroarylalkyl group; and B stands for a carboxyl group or a protected carboxyl group.

  本发明的目的是提供一种作为药物具有优异活性的醌衍生物。 本发明提供了一种由通式（I）代表的醌衍生物或其药理学上可接受的盐： 其中 A 代表由式表示的基团： (其中 R³、R⁴ 和 R⁵ 彼此相同或不同，且各自代表氢原子、羟基、低级烷基、低级烷氧基、烷氧基烷基、烷氧基烷氧基、环烷氧基烷基、硫醇基或硫代烷基，但 R³ 和 R⁴ 同时各自为低级烷氧基的情况除外）或由式表示的基团： (其中，R³、R⁴ 和 R⁵ 相互相同或不同，各自代表氢原子、羟基、低级烷基、低级烷氧基、烷氧基烷基、烷氧基烷氧基、环烷氧基烷基、硫醇基或硫代烷基，但 R³ 和 R⁴ 同时各自代表低级烷氧基的情况除外；X 和 Y 彼此相同或不同，各自代表一个羟基或一个受保护的羟基）； R¹ 代表杂芳基烷基；以及 B 代表羧基或受保护的羧基。
• 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.