ethyl 2-chloromethyl-4-(4-chlorophenyl)-6,7-dimethoxyquinoline-3-carboxylate | 153394-47-9

• 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 2-chloromethyl-4-(4-chlorophenyl)-6,7-dimethoxyquinoline-3-carboxylate
• 英文别名: ethyl 2-(chloromethyl)-4-(4-chlorophenyl)-6,7-dimethoxyquinoline-3-carboxylate
• CAS: 153394-47-9
• 化学式: C₂₁H₁₉Cl₂NO₄
• 分子量: 420.292
• InChiKey: IRSUOOPFGAFMJV-UHFFFAOYSA-N

物化性质

• 沸点：
  539.4±50.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  57.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲巯咪唑 、 ethyl 2-chloromethyl-4-(4-chlorophenyl)-6,7-dimethoxyquinoline-3-carboxylate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以71%的产率得到Ethyl 4-(4-chlorophenyl)-6,7-dimethoxy-2-[(1-methylimidazol-2-yl)sulfanylmethyl]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：

  4-氯乙酰乙酸乙酯 、 (2-amino-4,5-dimethoxyphenyl)-(4-chlorophenyl)methanone 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 生成 ethyl 2-chloromethyl-4-(4-chlorophenyl)-6,7-dimethoxyquinoline-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：US05650410A1

  公开（公告）日：1997-07-22

  This invention provides an anti-inflammatory agent, particularly an agent for treating arthritis, containing a quinoline or quinazoline derivative or a salt thereof ##STR1## wherein Y is a nitrogen atom or C--G in which G is an optionally esterified carboxyl group; R.sup.1 and R.sup.2 are each independently a hydrogen atom, optionally substituted hydrocarbon group or optionally substituted heterocyclic group, or R.sup.1 and R.sup.2 are linked together to form a saturated ring; each of the ring A and ring B may optionally be substituted; n is an integer of 1 to 4; and k is 0 or 1. This invention also provides a novel quinoline or quinazoline derivative having anti-inflammatory activity.

  该发明提供了一种抗炎剂，特别是一种用于治疗关节炎的剂，其含有喹啉或喹嗪衍生物或其盐##STR1##其中，Y是氮原子或C--G，其中G是可选的酯化羧基；R.sup.1和R.sup.2各自独立地是氢原子，可选的取代烃基或可选的取代杂环基，或R.sup.1和R.sup.2相互连接形成饱和环；环A和环B中的每一个都可以选择性地被取代；n是1到4的整数；k为0或1。该发明还提供了一种具有抗炎活性的新型喹啉或喹嗪衍生物。
• US5650410A
  申请人：——

  公开号：US5650410A

  公开（公告）日：1997-07-22
• 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.