ethyl 6,7-dimethoxy-4-(4-methoxyphenyl)-2-›(1-[methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate

• 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 6,7-dimethoxy-4-(4-methoxyphenyl)-2-›(1-[methylimidazol-2-yl)thiomethyl]quinoline-3-carboxylate
• 英文别名: Ethyl 6,7-dimethoxy-4-(4-methoxyphenyl)-2-[(1-methylimidazol-2-yl)sulfanylmethyl]quinoline-3-carboxylate
• 化学式: C₂₆H₂₇N₃O₅S
• 分子量: 493.583
• InChiKey: ALDTXAGSAHBYAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-Amino-4,5,4'-trimethoxy-benzophenon 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 6,7-dimethoxy-4-(4-methoxyphenyl)-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

• 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。
• US5948782A
  申请人：——

  公开号：US5948782A

  公开（公告）日：1999-09-07
• Studies on Disease-Modifying Antirheumatic Drugs:  Synthesis of Novel Quinoline and Quinazoline Derivatives and Their Anti-inflammatory Effect
  作者：Atsuo Baba、Noriaki Kawamura、Haruhiko Makino、Yoshikazu Ohta、Shigehisa Taketomi、Takashi Sohda

  DOI：10.1021/jm9509408

  日期：1996.1.1

  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.