2-Ethyl-6-(2,2,2-trifluoroethoxy)-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride | 135016-33-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-Ethyl-6-(2,2,2-trifluoroethoxy)-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride
• 英文别名: 2-ethyl-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methoxy]-6-(2,2,2-trifluoroethoxy)quinoline;hydrochloride
• CAS: 135016-33-0
• 化学式: C₂₇H₂₂F₃N₅O₂*ClH
• 分子量: 541.96
• InChiKey: XNWYBQUFVGSULS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.59
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  85.8
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-(2,2,2-三氟乙氧基)苯胺 在 盐酸 、 diphenyl ether-biphenyl eutectic 、 sodium hydride 、 对甲苯磺酸 作用下， 以 甲醇 、 乙醇 、 环己烷 为溶剂， 反应 29.25h， 生成 2-Ethyl-6-(2,2,2-trifluoroethoxy)-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride
  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

• Quinoline derivatives, process for their preparation and their use as medicaments
  申请人：ZENECA LIMITED

  公开号：EP0412848B1

  公开（公告）日：1995-01-18
• US5444071A
  申请人：——

  公开号：US5444071A

  公开（公告）日：1995-08-22
• 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.