6-methoxy-4,5,7-trimethyl-2-(3-pyridinecarboxamido)benzothiazole | 145096-38-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 6-methoxy-4,5,7-trimethyl-2-(3-pyridinecarboxamido)benzothiazole
• 英文别名: 3-Pyridinecarboxamide,n-(6-methoxy-4,5,7-trimethyl-2-benzothiazolyl)-；N-(6-methoxy-4,5,7-trimethyl-1,3-benzothiazol-2-yl)pyridine-3-carboxamide
• CAS: 145096-38-4
• 化学式: C₁₇H₁₇N₃O₂S
• 分子量: 327.407
• InChiKey: LFEMGJZYGUPYGJ-UHFFFAOYSA-N

物化性质

• 密度：
  1.303±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-methoxy-4,5,7-trimethyl-2-(3-pyridinecarboxamido)benzothiazole 在 盐酸 、 硼烷 、 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 1.25h， 生成 6-Hydroxy-4,5,7-trimethyl-2-(pyridin-3-ylmethyl)aminobenzothiazole
  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：

  氯化烟碱盐酸盐 、 6-甲氧基-4,5,7-三甲基-1,3-苯并噻唑-2-胺 在 吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以83%的产率得到6-methoxy-4,5,7-trimethyl-2-(3-pyridinecarboxamido)benzothiazole
  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

• Benzothiazole derivative
  申请人：Eisai Co., Ltd.

  公开号：EP0507318B1

  公开（公告）日：1997-09-10
• SUBSTITUTED FUSED AND BRIDGED BICYCLIC COMPOUNDS AS THERAPEUTIC AGENTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP0758312A1

  公开（公告）日：1997-02-19
• EP0758312A4
  申请人：——

  公开号：EP0758312A4

  公开（公告）日：1997-09-10
• US5300518A
  申请人：——

  公开号：US5300518A

  公开（公告）日：1994-04-05
• US5420144A
  申请人：——

  公开号：US5420144A

  公开（公告）日：1995-05-30