4-[(1E)-3-({2-[2,4-dichloro(methyl)-3-({[2-methyl-4-(1H-1,2,4-triazol-1-yl)-8-quinolinyl]oxy}methyl)anilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-N,N-dimethylbenzamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-[(1E)-3-({2-[2,4-dichloro(methyl)-3-({[2-methyl-4-(1H-1,2,4-triazol-1-yl)-8-quinolinyl]oxy}methyl)anilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-N,N-dimethylbenzamide
• 英文别名: 8-[2,6-Dichloro-3-[N-methyl-N-[4-(dimethylcarbamoyl)cinnamoylglycyl]amino]benzyloxy]-2-methyl-4-(1,2,4-triazol-1-yl)quinoline；4-[(E)-3-[[2-[2,4-dichloro-N-methyl-3-[[2-methyl-4-(1,2,4-triazol-1-yl)quinolin-8-yl]oxymethyl]anilino]-2-oxoethyl]amino]-3-oxoprop-1-enyl]-N,N-dimethylbenzamide
• 化学式: C₃₄H₃₁Cl₂N₇O₄
• 分子量: 672.571
• InChiKey: BFYDBRPENDXCMU-XNTDXEJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-羟基-8-甲氧基-2-甲基喹啉 在 三溴化硼 、 potassium carbonate 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 4-[(1E)-3-({2-[2,4-dichloro(methyl)-3-({[2-methyl-4-(1H-1,2,4-triazol-1-yl)-8-quinolinyl]oxy}methyl)anilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-N,N-dimethylbenzamide
  参考文献：
  名称：

  A New Series of Highly Potent Non-Peptide Bradykinin B₂ Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference

  摘要：

  Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B-2 receptor antagonists resulted in enhancing binding affinities for the human B-2 receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B-2 receptor but not for the guinea pig one. A series of 4-(I-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [H-3]BK to the cloned human B-2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 mug/kg by intravenous administration.

  DOI：

  10.1021/jm030159x

文献信息

• QUINOLINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION, AND THEIR USE AS MEDICAMENTS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0900203B1

  公开（公告）日：2003-03-19
• US6083959A
  申请人：——

  公开号：US6083959A

  公开（公告）日：2000-07-04
• A New Series of Highly Potent Non-Peptide Bradykinin B₂ Receptor Antagonists Incorporating the 4-Heteroarylquinoline Framework. Improvement of Aqueous Solubility and New Insights into Species Difference
  作者：Yuki Sawada、Hiroshi Kayakiri、Yoshito Abe、Keisuke Imai、Tsuyoshi Mizutani、Noriaki Inamura、Masayuki Asano、Ichiro Aramori、Chie Hatori、Akira Katayama、Teruo Oku、Hirokazu Tanaka

  DOI：10.1021/jm030159x

  日期：2004.3.1

  Introduction of nitrogen-containing heteroaromatic groups at the 4-position of the quinoline moiety of our non-peptide B-2 receptor antagonists resulted in enhancing binding affinities for the human B-2 receptor and reducing binding affinities for the guinea pig one, providing new structural insights into species difference. A CoMFA study focused on the diversity of the quinoline moiety afforded correlative and predictive QSAR models of binding for the human B-2 receptor but not for the guinea pig one. A series of 4-(I-imidazolyl)quinoline derivatives could be dissolved in a 5% aqueous solution of citric acid up to a concentration of 10 mg/mL. A representative compound 48a inhibited the specific binding of [H-3]BK to the cloned human B-2 receptor expressed in Chinese hamster ovary cells with an IC50 value of 0.26 nM and significantly inhibited BK-induced bronchoconstriction in guinea pigs even at 1 mug/kg by intravenous administration.