7-乙基-5-甲氧基-2-(甲基氨基)-4-(3-吡啶基甲基)-1,3-苯并噻唑-6-醇 | 763897-60-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 中文名称: 7-乙基-5-甲氧基-2-(甲基氨基)-4-(3-吡啶基甲基)-1,3-苯并噻唑-6-醇
• 英文名称: 7-Ethyl-5-methoxy-2-methylamino-4-pyridin-3-ylmethyl-benzothiazol-6-ol
• 英文别名: 7-Ethyl-5-methoxy-2-(methylamino)-4-(3-pyridinylmethyl)-1,3-benzothiazol-6-ol；7-ethyl-5-methoxy-2-(methylamino)-4-(pyridin-3-ylmethyl)-1,3-benzothiazol-6-ol
• CAS: 763897-60-5
• 化学式: C₁₇H₁₉N₃O₂S
• 分子量: 329.423
• InChiKey: DJDVLAQLBAQKTR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Acetic acid (4-ethyl-2,3,6-trimethoxy-phenyl)-pyridin-3-yl-methyl ester 在 盐酸 、 ammonium cerium(IV) nitrate 、 溶剂黄146 、 锌 作用下， 以 乙醇 为溶剂， 反应 29.0h， 生成 7-乙基-5-甲氧基-2-(甲基氨基)-4-(3-吡啶基甲基)-1,3-苯并噻唑-6-醇
  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.