2-ethyl-1,5,6,7-tetrahydro-4(1H)-cyclopentapyridone | 147330-29-8

• 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-ethyl-1,5,6,7-tetrahydro-4(1H)-cyclopentapyridone
• 英文别名: 2-ethyl-1,5,6,7-tetrahydro-4(1H)-cyclopenta[b]pyridone；2-Ethyl-1,5,6,7-tetrahydrocyclopenta[b]pyridin-4-one
• CAS: 147330-29-8
• 化学式: C₁₀H₁₃NO
• 分子量: 163.219
• InChiKey: HLRYUKVBXLQGTR-UHFFFAOYSA-N

物化性质

• 沸点：
  291.2±33.0 °C(Predicted)
• 密度：
  1.10±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-ethyl-1,5,6,7-tetrahydro-4(1H)-cyclopentapyridone 在 盐酸 、 sodium hydride 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 3.5h， 生成 6,7-dihydro-2-ethyl-4-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methoxy]-5H-cyclopenta[b]pyridine 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：

  N-(1-环戊烯基)吗啉 、 5-(1-hydroxypropylidene)-2,2-dimethyl-[1,3]dioxane-4,6-dione 在 氨 作用下， 生成 2-ethyl-1,5,6,7-tetrahydro-4(1H)-cyclopentapyridone 、 4-(1,3-dioxopentyl)morpholine
  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

• 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。
• Boron compounds
  申请人：ZENECA LIMITED

  公开号：EP0495627A1

  公开（公告）日：1992-07-22

  The invention concerns novel boron compounds of the formula IV, in which Q, Y¹, G¹ and G² 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.

  本发明涉及式 IV 的新型硼化合物（其中 Q、Y¹、G¹ 和 G² 具有本文所定义的各种含义）及其酸和碱加成盐。上述化合物可用于制造某些具有血管紧张素 II 抑制活性的喹啉、吡啶和咪唑衍生物。本发明还提供了生产喹啉、吡啶和咪唑衍生物的新工艺。
• 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
• US5245035A
  申请人：——

  公开号：US5245035A

  公开（公告）日：1993-09-14