N-[2,4-dichloro-3-({[4-(1H-imidazol-1-yl)-2-methyl-8-quinolinyl]oxy}methyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide | 199106-14-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-[2,4-dichloro-3-({[4-(1H-imidazol-1-yl)-2-methyl-8-quinolinyl]oxy}methyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide
• 英文别名: 8-[2,6-dichloro-3-(N-phthalimidoacetyl-N-methylamino)benzyloxy]-4-(imidazol-1-yl)-2-methylquinoline；N-[2,4-dichloro-3-[(4-imidazol-1-yl-2-methylquinolin-8-yl)oxymethyl]phenyl]-2-(1,3-dioxoisoindol-2-yl)-N-methylacetamide
• CAS: 199106-14-4
• 化学式: C₃₁H₂₃Cl₂N₅O₄
• 分子量: 600.461
• InChiKey: KPENDYOOKDLXRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  97.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[2,4-dichloro-3-({[4-(1H-imidazol-1-yl)-2-methyl-8-quinolinyl]oxy}methyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide 在 一水合肼 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-{[({2-[2,4-dichloro-3-({[4-(1H-imidazol-1-yl)-2-methyl-8-quinolinyl]oxy}methyl)methylanilino]-2-oxoethyl}amino)carbonyl]amino}-N-(4-pyridinyl)benzamide
  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
• 作为产物：
  描述：

  ethyl 3-<(2-methoxyphenyl)amino>but-2-enoate 在 4 A molecular sieve 、 三溴化硼 、 四丁基碘化铵 、 potassium carbonate 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 N-[2,4-dichloro-3-({[4-(1H-imidazol-1-yl)-2-methyl-8-quinolinyl]oxy}methyl)phenyl]-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-methylacetamide
  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
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06083959A1

  公开（公告）日：2000-07-04

  A compound of the formula: ##STR1## wherein R.sup.1 is lower alkyl, R.sup.2 is hydrogen, lower alkyl or a heterocyclic group, R.sup.3 is hydrogen, lower alkyl or halogen, R.sup.4 is lower alkyl or halogen, R.sup.5 is nitro or amino substituted with substituent(s) selected from the group consisting of lower alkyl and acyl, and A is lower alkylene.

  一种化合物的化学式：##STR1## 其中 R.sup.1 是较低的烷基，R.sup.2 是氢、较低烷基或杂环基，R.sup.3 是氢、较低烷基或卤素，R.sup.4 是较低烷基或卤素，R.sup.5 是硝基或氨基，带有从较低烷基和酰基的取代基选取的取代基，A 是较低的亚烯基。
• 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