ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate | 153394-76-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate
• 英文别名: ethyl 6,7-dimethoxy-4-(3,4-dimethoxyphenyl)-2-›(1-[methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate；ethyl 6,7-dimethoxy-4-(3,4-dimethoxyphenyl)-2-[(1-methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate；ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)sulfanylmethyl]quinoline-3-carboxylate
• CAS: 153394-76-4
• 化学式: C₂₇H₂₉N₃O₆S
• 分子量: 523.61
• InChiKey: HXODFOOYQHNNGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  119
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以58%的产率得到ethyl 6,7-dimethoxy-4-(3,4-dimethoxyphenyl)-2-›(1-[methylimidazol-2-yl)sulfinylmethyl]quinoline-3-carboxylate
  参考文献：
  名称：

  Studies on Disease-Modifying Antirheumatic Drugs:  Synthesis of Novel Quinoline and Quinazoline Derivatives and Their Anti-inflammatory Effect

  摘要：

  In the course of our study aimed at developing new types of DMARDs (disease-modifying antirheumatic drugs), we found that quinoline derivative 1a had a potent anti-inflammatory effect in an adjuvant arthritis (AA) rat model, starting from the potent bone resorption inhibitors justicidins as the lead compounds. Further modification of la was performed, and various quinoline and quinazoline derivatives having a heteroaryl moiety on the alkyl side chain at the 2-position of the skeleton were prepared. These compounds were evaluated for antiinflammatory effects using the AA rat model. Most of these compounds, especially those having an imidazole or a triazole moiety on the 2-alkyl chain, exhibited a potent effect. Among the compounds synthesized, ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-yl-methyl)quinoline-3-carboxylate (12d), having an ED(50) value of 2.6 mg/kg/day (anti-inflammatory effect in an AA rat model, po), was selected as a candidate for further investigation. In vitro, 12d inhibited mitogen-induced proliferation at 10(-7)-10(-5) M but not prostaglandin E(2) production at 10(-5) M. Moreover, 12d preferentially inhibited the IFN-gamma production by Th1-type clones over the IL-4 production by Th2-type clones. This preferential suppression of Th1 cytokine production is considered the essential immunomodulating action of 12d for the present. Synthesis and structure-activity relationships for this novel series of quinoline and quinazoline derivatives are detailed.

  DOI：

  10.1021/jm9509408
• 作为产物：
  描述：

  (2-amino-4,5-dimethoxyphenyl)(3,4-dimethoxyphenyl)methanone 在 硫酸 、 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate
  参考文献：
  名称：

  Studies on Disease-Modifying Antirheumatic Drugs:  Synthesis of Novel Quinoline and Quinazoline Derivatives and Their Anti-inflammatory Effect

  摘要：

  In the course of our study aimed at developing new types of DMARDs (disease-modifying antirheumatic drugs), we found that quinoline derivative 1a had a potent anti-inflammatory effect in an adjuvant arthritis (AA) rat model, starting from the potent bone resorption inhibitors justicidins as the lead compounds. Further modification of la was performed, and various quinoline and quinazoline derivatives having a heteroaryl moiety on the alkyl side chain at the 2-position of the skeleton were prepared. These compounds were evaluated for antiinflammatory effects using the AA rat model. Most of these compounds, especially those having an imidazole or a triazole moiety on the 2-alkyl chain, exhibited a potent effect. Among the compounds synthesized, ethyl 4-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2-(1,2,4-triazol-1-yl-methyl)quinoline-3-carboxylate (12d), having an ED(50) value of 2.6 mg/kg/day (anti-inflammatory effect in an AA rat model, po), was selected as a candidate for further investigation. In vitro, 12d inhibited mitogen-induced proliferation at 10(-7)-10(-5) M but not prostaglandin E(2) production at 10(-5) M. Moreover, 12d preferentially inhibited the IFN-gamma production by Th1-type clones over the IL-4 production by Th2-type clones. This preferential suppression of Th1 cytokine production is considered the essential immunomodulating action of 12d for the present. Synthesis and structure-activity relationships for this novel series of quinoline and quinazoline derivatives are detailed.

  DOI：

  10.1021/jm9509408

文献信息

• Pharmaceutical composition containing quinoline or quinazoline
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05719157A1

  公开（公告）日：1998-02-17

  The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.

  本发明提供了一种用于抑制骨吸收或预防/治疗骨质疏松症的药物组合物，其包含喹啉或喹啉衍生物作为活性成分。
• Pharmaceutical composition containing quinoline and quinazoline
  申请人：Takeda Chemical

  公开号：US05948782A1

  公开（公告）日：1999-09-07

  There is disclosed an anti-inflammatory agent comprising a compound of the formula (I): ##STR1## The quinoline compounds included in the compound (I) are novel and there is also disclosed processes for producing them.

  本发明揭示了一种包括化合物(I)的抗炎药剂：##STR1## 化合物(I)中包括的喹啉化合物是新颖的，同时还揭示了生产它们的方法。
• Quinoline and quinazoline derivatives for treating arthritis
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0567107A1

  公开（公告）日：1993-10-27

  There is disclosed an anti-inflammatory agent comprising a compound of the formula (I): The quinoline compounds included in the compound (I) are novel and there is also disclosed processes for producing them.

  本发明公开了一种由式 (I) 化合物组成的抗炎剂： 化合物(I)中包含的喹啉化合物是新颖的，同时也公开了其生产工艺。
• Pharmaceutical composition containing quinoline or quinazoline derivatives
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0634169A1

  公开（公告）日：1995-01-18

  The present invention provides a pharmaceutical composition for inhibiting bone resorption or for preventing or treating osteoporosis which comprises a quinoline or quinazoine derivative as an active ingredient.

  本发明提供了一种用于抑制骨吸收或预防或治疗骨质疏松症的药物组合物，其活性成分包括喹啉或喹唑啉衍生物。
• Quinoline or quinazoline derivatives and their use in the manufacture of a medicament for the treatment of osteoporosis
  申请人：TAKEDA CHEMICAL INDUSTRIES, LTD.

  公开号：EP0634169B1

  公开（公告）日：2000-01-05