2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylic acid methyl ester | 153394-49-1

• 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: 2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylic acid methyl ester
• 英文别名: methyl 2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylate；Methyl 2-(chloromethyl)-4-(3,4-dimethoxyphenyl)-6,7-dimethoxyquinoline-3-carboxylate
• CAS: 153394-49-1
• 化学式: C₂₂H₂₂ClNO₆
• 分子量: 431.873
• InChiKey: HURFFWJKFBSESL-UHFFFAOYSA-N

物化性质

• 沸点：
  548.3±50.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1H-1,2,4-三唑 、 2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylic acid methyl ester 生成 6,7-dimethoxy-4-(3,4-dimethoxyphenyl)-2-(1,2,4-triazol-1-ylmethyl)quinoline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Quinoline or quinazoline derivatives, their production and use

  摘要：

  一种由通式表示的化合物：##STR1## 其中Y代表一个氮原子或C--G（G代表一个可能酯化的羧基）；环R是一个含氮的不饱和杂环基团，可以被取代或未取代；环A和环B中的每一个都可以有一个取代基；n代表一个从1到4的整数；k代表整数0或1，或其盐，可作为一种抗炎药物，特别是治疗关节炎的药物。

  公开号：

  US05436247A1
• 作为产物：
  描述：

  4-氯乙酰乙酸甲酯 、 (2-amino-4,5-dimethoxyphenyl)(3,4-dimethoxyphenyl)methanone 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 生成 2-chloromethyl-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)quinoline-3-carboxylic acid methyl ester
  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 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
• US5436247A
  申请人：——

  公开号：US5436247A

  公开（公告）日：1995-07-25
• US5719157A
  申请人：——

  公开号：US5719157A

  公开（公告）日：1998-02-17
• US5770602A
  申请人：——

  公开号：US5770602A

  公开（公告）日：1998-06-23