3-(2,3,6-Trimethoxy-4-methyl-benzyl)-pyridine | 1026306-80-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(2,3,6-Trimethoxy-4-methyl-benzyl)-pyridine
• 英文别名: 3-[(2,3,6-Trimethoxy-4-methylphenyl)methyl]pyridine
• CAS: 1026306-80-8
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: TWCNWBSAKKCNLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2,3,6-Trimethoxy-4-methyl-benzyl)-pyridine 在 ammonium cerium(IV) nitrate 作用下， 生成 3-Methoxy-5-methyl-2-(pyridin-3-ylmethyl)cyclohexa-2,5-diene-1,4-dione
  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：

  Pyridin-3-yl-(2,3,6-trimethoxy-4-methyl-phenyl)-methanol 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 生成 3-(2,3,6-Trimethoxy-4-methyl-benzyl)-pyridine
  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

• 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.