2,6-dimethyl-3-(3-pyridylmethyl)-1,4-benzoquinone | 158500-85-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,6-dimethyl-3-(3-pyridylmethyl)-1,4-benzoquinone
• 英文别名: 3,5-Dimethyl-2-(pyridin-3-ylmethyl)cyclohexa-2,5-diene-1,4-dione
• CAS: 158500-85-7
• 化学式: C₁₄H₁₃NO₂
• 分子量: 227.263
• InChiKey: VETPUUZYTKJCLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  47
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-甲硫脲 、 2,6-dimethyl-3-(3-pyridylmethyl)-1,4-benzoquinone 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 24.0h， 以83%的产率得到6-hydroxy-5,7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl)benzothiazole dihydrochloride
  参考文献：
  名称：

  Novel Dual Inhibitors of 5-Lipoxygenase and Thromboxane A2 Synthetase: Synthesis and Structure-Activity Relationships of 3-Pyridylmethyl-Substituted 2-Amino-6-hydroxybenzothiazole Derivatives

  摘要：

  As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B-4 (LTB(4)) and thromboxane A(2) (TXA(2)), while not significantly inhibiting that of prostaglandin E(2) (PGE(2)). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-Lipoxygenase and TXA(2) synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE(2) production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA(2) synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA(2) synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/ kg), the production of both LTB(4) and TXB(2) in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4 zole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.

  DOI：

  10.1021/jm00045a011
• 作为产物：
  描述：

  α-(pyridin-3-yl)-2,5-dimethoxy-4,6-dimethylbenzyl acetate 在 palladium on activated charcoal ammonium cerium(IV) nitrate 、 氢气 作用下， 生成 2,6-dimethyl-3-(3-pyridylmethyl)-1,4-benzoquinone
  参考文献：
  名称：

  Novel Dual Inhibitors of 5-Lipoxygenase and Thromboxane A2 Synthetase: Synthesis and Structure-Activity Relationships of 3-Pyridylmethyl-Substituted 2-Amino-6-hydroxybenzothiazole Derivatives

  摘要：

  As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B-4 (LTB(4)) and thromboxane A(2) (TXA(2)), while not significantly inhibiting that of prostaglandin E(2) (PGE(2)). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-Lipoxygenase and TXA(2) synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE(2) production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA(2) synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA(2) synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/ kg), the production of both LTB(4) and TXB(2) in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4 zole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.

  DOI：

  10.1021/jm00045a011

文献信息

• Synthesis of 14C-labelled 6-hydroxy-5,7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl)benzothiazole dihydrochloride (14C-E3040 dihydrochloride)
  作者：Shigeki Hibi、Hirotoshi Numata、Yasushi Okamoto、Osamu Takenaka、Mannen Mishima

  DOI：10.1002/jlcr.2580360507

  日期：1995.5

  14C-Labelled 6-hydroxy-5,7-dimethyl-2-(methylamino)-4-(3-pyridylmethyl)-benzothiazole dihydrochloride (14C-E3040 dihydrochloride), required for a study of the phrmacokinetic profile of E3040, a novel dual inhibitor of 5-lipoxygenase and thromboxane A2 synthetase, was synthesized in one step using [2-14C]-1-methyl-2-thiourea as the labelled starting material. 14C-E3040 dihydrochloride with a specific activity of 58.0mCi/mmol was prepared in 60% chemical yield(based on thiourea 2).

  14C 标记的 6-羟基-5,7-二甲基-2-(甲基氨基)-4-(3-吡啶基甲基)-苯并噻唑二盐酸盐（14C-E3040 二盐酸盐）是研究新型 5-脂氧合酶和血栓素 A2 合成酶双重抑制剂 E3040 的短链分子动力学特征所必需的，它是以[2-14C]-1-甲基-2-硫脲为标记起始材料一步合成的。制备的 14C-E3040 二盐酸盐的化学收率为 60%（基于硫脲 2），比活性为 58.0mCi/mmol。
• Novel Dual Inhibitors of 5-Lipoxygenase and Thromboxane A2 Synthetase: Synthesis and Structure-Activity Relationships of 3-Pyridylmethyl-Substituted 2-Amino-6-hydroxybenzothiazole Derivatives
  作者：Shigeki Hibi、Yasushi Okamoto、Katsuya Tagami、Hirotoshi Numata、Naoki Kobayashi、Masanobu Shinoda、Tetsuya Kawahara、Manabu Murakami、Kiyoshi Oketani

  DOI：10.1021/jm00045a011

  日期：1994.9

  As part of our search for novel antiinflammatory drug candidates, we have designed and synthesized a series of 3-pyridylmethyl-substituted 2-amino-6-hydroxybenzothiazoles. Introduction of a 3-pyridylmethyl group into the 2-amino group (type-A) or the benzene ring (type-B) of 2-amino-6-hydroxybenzothiazoles imparted dual inhibitory activity against the production by glycogen-induced peritoneal cells of rat (in vitro) of leukotriene B-4 (LTB(4)) and thromboxane A(2) (TXA(2)), while not significantly inhibiting that of prostaglandin E(2) (PGE(2)). The observed inhibition of the former two arachidonic acid metabolites was indicated to be the result of a direct action on 5-Lipoxygenase and TXA(2) synthetase by a cell-free in vitro assay. On the other hand, the inhibitory activities against PGE(2) production were for most compounds very weak, indicating that they did not inhibit cyclooxygenase. Structure-activity relationship studies concerning the position of the 3-pyridylmethyl group revealed that type-B compounds generally showed about 10-fold stronger inhibitory activity against TXA(2) synthetase than type-A compounds. The position of the 3-pyridylmethyl group played an important role in TXA(2) synthetase inhibition. When some of these compounds (8, 13a, 26a (E3040), 26b, 27b, and 28b) were orally administered in the rat TNB/ethanol-induced chronic colitis model (100 mg/ kg), the production of both LTB(4) and TXB(2) in the rat colon was reduced (ex vivo). In addition, one type-B compound, 6-hydroxy-5,7-dimethyl-2-(methylamino)-4 zole (26a), demonstrated a therapeutic effect at treatments of 100 mg/kg po once daily for 11 days and showed almost comparable activity to sulfasalazine at a dose of 500 mg/kg, the reference drug for inflammatory bowel diseases, in this in vivo model.