ZD 8731 | 135015-84-8

• 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: ZD 8731
• 英文别名: 2-ethyl-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]quinoline hydrochloride；2-Ethyl-4-((2'-(2H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methoxy)quinoline hydrochloride；2-ethyl-4-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methoxy]quinoline;hydrochloride
• CAS: 135015-84-8
• 化学式: C₂₅H₂₁N₅O*ClH
• 分子量: 443.936
• InChiKey: UDVVSNKCOWXHSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.65
• 重原子数：
  32
• 可旋转键数：
  6
• 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 、 sodium hydride 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 22.0h， 生成 ZD 8731
  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

• Chemical process for making angiotesin II antagonist compounds
  申请人：Imperial Chemical Industries PLC

  公开号：US05294716A1

  公开（公告）日：1994-03-15

  The invention provides a novel chemical process for the manufacture of quinoline, pyridine and imidazole derivatives of the formula IV wherein Q, Y.sup.1 and Y.sup.2 have the various meanings defined herein, and their non-toxic salts, which are angiotensin II inhibitors. The process involves the removal of an electron-deficient phenyl group or a pyridyl or pyrimidyl group from a compound of the formula VI as defined herein.

  该发明提供了一种新颖的化学过程，用于制造公式IV中Q、Y.sup.1和Y.sup.2具有本文定义的各种含义的喹啉、吡啶和咪唑衍生物，以及它们的无毒盐，这些物质是血管紧张素II抑制剂。该过程涉及从本文定义的公式VI中去除一个电子亏缺的苯基或吡啶基或嘧啶基。
• Process for the preparation of tetrazole derivatives
  申请人：ZENECA LIMITED

  公开号：EP0495626A1

  公开（公告）日：1992-07-22

  A compound of formula VI wherein Q is selected from (substituted) 4-quinolyloxy, (substituted) 4-pyridyloxy and substituted 1-imidazolyl; Y¹ is selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, (1-4C)alkanoyl, trifluoromethyl, cyano and nitro; Y² is selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano and nitro; and P¹ is an electron-deficient phenyl group or a pyridyl or pyrimidyl group, is reacted with a base selected from an alkali metal hydroxide, (1-12C)alkanolate, (1-12C)alkanethiolate, phenolate, thiophenolate and diphenylphosphide, wherein any phenyl ring of the latter three groups may optionally bear a (1-4C)alkyl, (1-4C)alkoxy or halogeno substituent; to give a compound of formula IV wherein Q, Y¹ and Y² have any of the meanings defined above. The compounds of formula IV are angiotensin II inhibitors.

  化合物VI的式子，其中Q选择自（取代的）4-喹诺氧基，（取代的）4-吡啶氧基和取代的1-咪唑基; Y¹选择自氢，（1-4C）烷基，（1-4C）烷氧基，卤素，（1-4C）酰基，三氟甲基，氰基和硝基; Y²选择自氢，（1-4C）烷基，（1-4C）烷氧基，卤素，三氟甲基，氰基和硝基; P¹是电子不足的苯基或吡啶基或嘧啶基，与从碱金属氢氧化物，（1-12C）烷基醇盐，（1-12C）烷硫醇盐，苯酚盐，硫苯酚盐和二苯基膦选择的碱基反应，其中后三个基团的任何苯环可以选择性地带有（1-4C）烷基，（1-4C）烷氧基或卤素取代基; 得到式子IV的化合物，其中Q，Y¹和Y²具有上述定义的任何含义。式子IV的化合物是血管紧张素II抑制剂。
• Biphenyl-tetrazole intermediate compounds
  申请人：Zeneca Limited

  公开号：US05420292A1

  公开（公告）日：1995-05-30

  The invention provides a novel chemical process for the manufacture of quinoline, pyridine and imidazole derivatives of the formula IV wherein Q, Y.sup.1 and Y.sup.2 have the various meanings defined herein, and their non-toxic salts, which are angiotensin II inhibitors. The process involves the removal of an electron-deficient phenyl group or a pyridyl or pyrimidyl group from a compound of the formula VI as defined herein. Certain of the intermediates are novel and are provided as a further feature of the invention.

  本发明提供了一种新的化学过程，用于制造式IV的喹啉、吡啶和咪唑衍生物，其中Q、Y.sup.1和Y.sup.2具有本文所定义的各种含义，以及它们的非毒性盐，它们是血管紧张素II抑制剂。该过程涉及从式VI所定义的化合物中去除一个电子不足的苯基或吡啶基或嘧啶基。其中某些中间体是新的，并作为本发明的另一特征提供。
• Quinoline derivatives and use thereof as angiotensin II antagonists
  申请人：Imperial Chemical Industries PLC

  公开号：US05444071A1

  公开（公告）日：1995-08-22

  The invention concerns pharmaceutically useful novel compounds of the formula I, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, Ra, A, 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. ##STR1##

  本发明涉及一种具有药用价值的新化合物，其化学式为I，在该式中，R.sup.1，R.sup.2，R.sup.3，R.sup.4，R.sup.5，Ra，A，X和Z具有定义于此处的各种含义，以及它们的非毒性盐和含有它们的药物组合物。这些新化合物对于治疗高血压和充血性心力衰竭等疾病具有价值。本发明还涉及制造这些新化合物的过程以及将这些化合物用于医疗治疗的用途。
• Heterocyclic boron compounds as intermediates for angiotensin II
  申请人：Imperial Chemical Industries PLC

  公开号：US05245035A1

  公开（公告）日：1993-09-14

  The invention concerns novel boron compounds of the formula IV, in which Q, Y.sup.1, G.sup.1 and G.sup.2 have the various meanings defined herein, and their acid and base addition salts. The said compounds are useful in the manufacture of certain quinoline, pyridine and imidazole derivatives which have angiotensin II inhibitory activity. The invention also provides novel processes for the production of the quinoline, pyridine and imidazole derivatives. ##STR1##

  本发明涉及一种新型的硼化合物，其化学式为IV，其中Q、Y1、G1和G2具有本文中定义的不同含义，以及它们的酸和碱盐。所述化合物在制造某些喹啉、吡啶和咪唑衍生物方面有用，这些衍生物具有血管紧张素II抑制活性。本发明还提供了制备喹啉、吡啶和咪唑衍生物的新方法。##STR1##