2-methyl-4-<1-<2'-(1H-tetrazol-5-yl)biphenyl-4-yl>ethoxy>quinoline hydrochloride | 138804-30-5

• 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-methyl-4-<1-<2'-(1H-tetrazol-5-yl)biphenyl-4-yl>ethoxy>quinoline hydrochloride
• 英文别名: 2-methyl-4-[1-(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)ethoxy]quinoline hydrochloride；2-methyl-4-{1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]ethoxy}quinoline hydrochloride；2-methyl-4-[1-[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]ethoxy]quinoline;hydrochloride
• CAS: 138804-30-5
• 化学式: C₂₅H₂₁N₅O*ClH
• 分子量: 443.936
• InChiKey: ZGVMVTLURSNGCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.95
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-(三苯基甲基)-5-(4'-溴甲基联苯-2-基)四氮唑 在 盐酸 、 锂硼氢 、 18-冠醚-6 、 三氧化硫吡啶 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醚 、 乙醇 、 二甲基亚砜 为溶剂， 反应 84.5h， 生成 2-methyl-4-<1-<2'-(1H-tetrazol-5-yl)biphenyl-4-yl>ethoxy>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

• Biphenylene branched alkyleneoxy quinolines
  申请人：Imperial Chemical Industries PLC

  公开号：US05369114A1

  公开（公告）日：1994-11-29

  There are disclosed quinolines of the formula ##STR1## wherein R.sup.1 is hydrogen, or hydrocarbyl. R.sub.3 and R.sub.4 are independently, H, alkyl, various functional groups or alkylenedioxy, X is phenylene optionally bearing a substituent, R.sub.a is (1-4)C alkyl optionally bearing one or more F's, Z is various carboxyl derivatives, useful as angiotensin II antagonists.

  公开了式子为##STR1##的喹啉，其中R.sup.1为氢或烃基。R.sub.3和R.sub.4分别为H，烷基，各种官能团或烷基二氧基，X为苯基，可选地带有取代基，R.sub.a为(1-4)C烷基，可选地带有一个或多个F，Z为各种羧酸衍生物，作为血管紧张素II拮抗剂有用。
• Quinoline derivatives, process for their preparation and their use as medicaments
  申请人：ZENECA LIMITED

  公开号：EP0456442A1

  公开（公告）日：1991-11-13

  The invention concerns pharmaceutically useful novel compounds of the formula I, in which R¹, R², R³, R⁴, R⁵, Ra, X and Z have the various meanings defined herein, and their non-toxic salts, and pharmaceutical compositions containing them. The novel compounds are of value in treating conditions such as hypertension and congestive heart failure. The invention further concerns processes for the manufacture of the novel compounds and the use of the compounds in medical treatment.

  本发明涉及式 I（其中 R¹、R²、R³、R⁴、R⁵、Ra、X 和 Z 具有本文定义的各种含义）的药用新型化合物及其无毒盐和含有它们的药物组合物。这些新型化合物具有治疗高血压和充血性心力衰竭等疾病的价值。本发明还涉及新型化合物的生产工艺以及这些化合物在医疗中的应用。
• JPH04225959A
  申请人：——

  公开号：JPH04225959A

  公开（公告）日：1992-08-14
• US5369114A
  申请人：——

  公开号：US5369114A

  公开（公告）日：1994-11-29