methyl 4'-<(3-ethyl-1,4-dihydro-4-oxoquinolinyl)methyl>biphenyl-2-carboxylate | 143494-69-3

• 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: methyl 4'-<(3-ethyl-1,4-dihydro-4-oxoquinolinyl)methyl>biphenyl-2-carboxylate
• 英文别名: Methyl 2-[4-[(3-ethyl-4-oxoquinolin-1-yl)methyl]phenyl]benzoate
• CAS: 143494-69-3
• 化学式: C₂₆H₂₃NO₃
• 分子量: 397.474
• InChiKey: BRAKAFLLDFPANM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4'-<(3-ethyl-1,4-dihydro-4-oxoquinolinyl)methyl>biphenyl-2-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以77%的产率得到4'-<(3-ethyl-1,4-dihydro-4-oxoquinolinyl)methyl>biphenyl-2-carboxylic acid
  参考文献：
  名称：

  New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives

  摘要：

  A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.01-1 muM. Structure-activity studies showed the quinoline nitrogen atom and a short alkyl chain at the quinoline 2-position to be essential for receptor binding. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-2.0 mg/kg. One of the compounds, 2-ethyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy]quinoline (5g), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg in AII-infused, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model, compound 5g showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg. On the basis of its profile, this compound, designated ICID8731, has been selected for clinical evaluation.

  DOI：

  10.1021/jm00100a007
• 作为产物：
  描述：

  ethyl 3-ethyl-1,4-dihydro-4-oxoquinoline-2-carboxylate 在 sodium hydroxide 、 正十二烷基苯 、 sodium hydride 作用下， 反应 18.08h， 生成 methyl 4'-<(3-ethyl-1,4-dihydro-4-oxoquinolinyl)methyl>biphenyl-2-carboxylate
  参考文献：
  名称：

  New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives

  摘要：

  A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.01-1 muM. Structure-activity studies showed the quinoline nitrogen atom and a short alkyl chain at the quinoline 2-position to be essential for receptor binding. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-2.0 mg/kg. One of the compounds, 2-ethyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy]quinoline (5g), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg in AII-infused, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model, compound 5g showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg. On the basis of its profile, this compound, designated ICID8731, has been selected for clinical evaluation.

  DOI：

  10.1021/jm00100a007

文献信息

• New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives
  作者：Robert H. Bradbury、Christopher P. Allott、Michael Dennis、Eric Fisher、John S. Major、Brian B. Masek、Alec A. Oldham、Robert J. Pearce、Neil Rankine

  DOI：10.1021/jm00100a007

  日期：1992.10

  A novel series of nonpeptidic angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylcarboxylic acid or biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 2-alkyl quinoline. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.01-1 muM. Structure-activity studies showed the quinoline nitrogen atom and a short alkyl chain at the quinoline 2-position to be essential for receptor binding. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-2.0 mg/kg. One of the compounds, 2-ethyl-4-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy]quinoline (5g), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg in AII-infused, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model, compound 5g showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg. On the basis of its profile, this compound, designated ICID8731, has been selected for clinical evaluation.