6-Methyl-2-propyl-4-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethoxy]-nicotinic acid methyl ester | 138620-90-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 6-Methyl-2-propyl-4-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethoxy]-nicotinic acid methyl ester
• 英文别名: Methyl 6-methyl-2-propyl-4-[[4-[2-(2-trityltetrazol-5-yl)phenyl]phenyl]methoxy]pyridine-3-carboxylate
• CAS: 138620-90-3
• 化学式: C₄₄H₃₉N₅O₃
• 分子量: 685.825
• InChiKey: JIWYTYLVKQXANS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10
• 重原子数：
  52
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  92
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-Methyl-2-propyl-4-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethoxy]-nicotinic acid methyl ester 在 盐酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 2.0h， 生成 methyl 6-methyl-2-propyl-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]pyridine-3-carboxylate hydrochloride
  参考文献：
  名称：

  New nonpeptide angiotensin II receptor antagonists. 3. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)pyridine derivatives

  摘要：

  A novel series of nonpeptide angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 3-substituted 2,6-dialkylpyridine. 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 0.005-0.5 muM. A variety of substituents was found to be effective at the 3-position of the pyridine ring. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-1.0 mg/kg. One of the compounds, 2-ethyl-5,6,7,8-tetrahydro-4-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy}quinoline (26), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg po in AII-infused, conscious, 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 26 showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg po. Based on its profile, this compound, designated ICI D6888, has been selected for evaluation in volunteers.

  DOI：

  10.1021/jm00061a016
• 作为产物：
  描述：

  3-aminohex-2-enoic acid methyl ester 在 sodium hydride 作用下， 反应 4.5h， 生成 6-Methyl-2-propyl-4-[2'-(2-trityl-2H-tetrazol-5-yl)-biphenyl-4-ylmethoxy]-nicotinic acid methyl ester
  参考文献：
  名称：

  New nonpeptide angiotensin II receptor antagonists. 3. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)pyridine derivatives

  摘要：

  A novel series of nonpeptide angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 3-substituted 2,6-dialkylpyridine. 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 0.005-0.5 muM. A variety of substituents was found to be effective at the 3-position of the pyridine ring. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-1.0 mg/kg. One of the compounds, 2-ethyl-5,6,7,8-tetrahydro-4-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy}quinoline (26), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg po in AII-infused, conscious, 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 26 showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg po. Based on its profile, this compound, designated ICI D6888, has been selected for evaluation in volunteers.

  DOI：

  10.1021/jm00061a016

文献信息

• Pyridine derivatives
  申请人：ZENECA LIMITED

  公开号：EP0453210A2

  公开（公告）日：1991-10-23

  The invention concerns pharmaceutically useful novel compounds of the formula I, 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.

  本发明涉及在医药上有用的式 I 新型化合物及其无毒盐，以及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用途。
• US5130318A
  申请人：——

  公开号：US5130318A

  公开（公告）日：1992-07-14
• US5198439A
  申请人：——

  公开号：US5198439A

  公开（公告）日：1993-03-30
• New nonpeptide angiotensin II receptor antagonists. 3. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)pyridine derivatives
  作者：Robert H. Bradbury、Christopher P. Allott、Michael Dennis、J. Alan Girdwood、Peter W. Kenny、John S. Major、Alec A. Oldham、Arnold H. Ratcliffe、Janet E. Rivett

  DOI：10.1021/jm00061a016

  日期：1993.4

  A novel series of nonpeptide angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 3-substituted 2,6-dialkylpyridine. 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 0.005-0.5 muM. A variety of substituents was found to be effective at the 3-position of the pyridine ring. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-1.0 mg/kg. One of the compounds, 2-ethyl-5,6,7,8-tetrahydro-4-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methoxy}quinoline (26), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg po in AII-infused, conscious, 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 26 showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg po. Based on its profile, this compound, designated ICI D6888, has been selected for evaluation in volunteers.