2,6-dimethyl-3-(4-pyridyl)-4(1H)-pyridone | 144173-58-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,6-dimethyl-3-(4-pyridyl)-4(1H)-pyridone
• 英文别名: 1,4-Dihydro-2,6-dimethyl-4-oxo-3-(4-pyridyl)pyridine；2,6-dimethyl-3-pyridin-4-yl-1H-pyridin-4-one
• CAS: 144173-58-0
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: OMHJPCNTUGHFGX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-dimethyl-3-(4-pyridyl)-4(1H)-pyridone 在 盐酸 、 sodium hydride 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.5h， 生成 2,6-Dimethyl-4-[2'-(1H-tetrazol-5-yl)-biphenyl-4-ylmethoxy]-[3,4']bipyridinyl; 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：

  2,6-dimethyl-3-(4-pyridyl)-4-pyrone 在 氨 作用下， 以 乙醇 为溶剂， 反应 67.0h， 以61%的产率得到2,6-dimethyl-3-(4-pyridyl)-4(1H)-pyridone
  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 compounds which have useful pharmaceutical utility
  申请人：Imperial Chemical Industries PLC

  公开号：US05380730A1

  公开（公告）日：1995-01-10

  The invention concerns pharmaceutically useful compounds of the formula I, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, 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.

  本发明涉及公式I的具有药用价值的化合物，其中R.sup.1，R.sup.2，R.sup.3，R.sup.4，R.sup.5，R.sup.6，R.sup.7，X和Z具有在此定义的各种含义，以及它们的非毒性盐和含有它们的药物组合物。这些新型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。本发明还涉及制造新型化合物的工艺以及在医疗治疗中使用这些化合物的方法。
• Pyridine compounds which are useful as angiotensin II receptor
  申请人：Imperial Chemical Industries PLC

  公开号：US05236936A1

  公开（公告）日：1993-08-17

  The invention concerns pharmaceutically useful compounds of the formula I, in which R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, 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.

  该发明涉及公式I的药用化合物，其中R.sup.1，R.sup.2，R.sup.3，R.sup.4，R.sup.5，R.sup.6，R.sup.7，X和Z具有本文所定义的各种含义，以及它们的非毒性盐和含有它们的制药组合物。这些新型化合物在治疗高血压和充血性心力衰竭等疾病方面具有价值。该发明还涉及新型化合物的制造过程以及化合物在医疗治疗中的应用。
• Pyridine compounds as angiotensin II antagonists, processes for their preparation and pharmaceutical compositions containing them
  申请人：ZENECA LIMITED

  公开号：EP0499416A2

  公开（公告）日：1992-08-19

  The invention concerns pharmaceutically useful compounds of formulae I-Ic, in which R1, R2, R3, R4, R5, R6, R7, 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-Ic 的药用化合物（其中 R1、R2、R3、R4、R5、R6、R7、X 和 Z 具有本文所定义的各种含义）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。
• US5236936A
  申请人：——

  公开号：US5236936A

  公开（公告）日：1993-08-17
• US5380730A
  申请人：——

  公开号：US5380730A

  公开（公告）日：1995-01-10