2-Ethyl-5-methoxy-1H-quinolin-4-one | 135016-09-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-Ethyl-5-methoxy-1H-quinolin-4-one
• CAS: 135016-09-0
• 化学式: C₁₂H₁₃NO₂
• 分子量: 203.241
• InChiKey: ALXVLZZAODPVBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氧代戊酸甲酯 在 diphenyl ether-biphenyl eutectic 、 对甲苯磺酸 作用下， 以 环己烷 为溶剂， 反应 7.25h， 生成 2-Ethyl-5-methoxy-1H-quinolin-4-one
  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

• Quinoline derivatives, process for their preparation and their use as medicaments
  申请人：ZENECA LIMITED

  公开号：EP0412848A2

  公开（公告）日：1991-02-13

  Quinoline deriviatives of the formula I wherein R¹ is hydrogen, (1-8C)alkyl, (3-8C)cycloalkyl, phenyl or substituted (1-4C)alkyl, the latter containing one or more fluoro substituents or bearing a (3-8C)cycloalkyl, hydroxy, (1-4C)alkoxy or phenyl substituent; R² is hydrogen, (1-8C)alkyl, (3-8C)cycloalkyl, (3-8C)cycloalkyl-(1-4C)alkyl, carboxy, (1-4C)alkoxycarbonyl, cyano, nitro, phenyl or phenyl(1-4C)alkyl; R³ and R⁴ are independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy, flouro(1-4C)alkoxy, halogeno, hydroxy, trifluoromethyl, cyano, nitro, amino, (1-4C)alkanoylamino, alkylamino and dialkylamino of up to 6 carbon atoms, dialkylamino-alkyl of 3 to 8 carbon atoms, (1-4C)alkanoyl, carbamoyl, N -alkylcarbamoyl and di-(N -alkyl)carbamoyl of up to 7 carbon atoms, carboxy, (1-4C)alkoxycarbonyl, (1-6C)alkylthio, (1-6C)alkylsulphinyl, (1-6C)alkylsulphonyl, and substituted (1-4C)alkyl, the latter bearing an amino, hydroxy or (1-4C)alkoxy substituent; or R³ and R⁴ together form (1-4C)alkylenedioxy attached to adjacent carbon atoms of the benzene moiety of formula I; Ra and R⁵ are independently selected from hydrogen, (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano and nitro; A is methylene; X is phenylene optionally bearing a substituent selected from (1-4C)alkyl, (1-4C)alkoxy, halogeno, trifluoromethyl, cyano and nitro, or X is a direct bond between the adjacent phenyl group and moiety A; Z is 1H -tetrazol-5-yl, -CO.NH.(1H -tetrazol-5-yl) or a group of the formula -CO.OR⁶ or -CO.NH.SO₂.R⁷ in which R⁶ is hydrogen or a non-toxic, biodegradable residue of a physiologically acceptable alcohol or phenol, and R⁷ is (1-6C)alkyl, (3-8C)cycloalkyl or phenyl; and wherein any of said phenyl moieties may be unsubsituted or bear one or two substituents independently selected from (1-4C)alkyl, (1-4C)alkoxy, halogeno, cyano and trifluoromethyl, their non-toxic salts, and pharmaceutical compositions containg them. The compounds of formula I are of value in treating conditions such as hyper-tension and congestive heart failure.

  式 I 的喹啉衍生物 其中R¹是氢、(1-8C)烷基、(3-8C)环烷基、苯基或取代的(1-4C)烷基，后者含有一个或多个氟取代基，或带有(3-8C)环烷基、羟基、(1-4C)烷氧基或苯基取代基；R² 是氢、(1-8C)烷基、(3-8C)环烷基、(3-8C)环烷基-(1-4C)烷基、羧基、(1-4C)烷氧基羰基、氰基、硝基、苯基或苯基(1-4C)烷基；R³ 和 R⁴ 独立选自氢、(1-4C)烷基、(1-4C)烷氧基、氟(1-4C)烷氧基、卤素、羟基、三氟甲基、氰基、硝基、氨基、(1-4C)烷酰氨基、最多 6 个碳原子的烷基氨基和二烷基氨基、3 至 8 个碳原子的二烷基氨基烷基、碳原子数不超过 7 个的(1-4C)烷酰基、氨基甲酰基、N-烷基氨基甲酰基和二-(N-烷基)氨基甲酰基、羧基、(1-4C)烷氧基羰基、(1-6C)烷硫基、(1-6C)烷基亚磺酰基、(1-6C)烷基磺酰基和取代的(1-4C)烷基，后者带有氨基、羟基或(1-4C)烷氧基取代基；或 R³ 和 R⁴ 共同形成 (1-4C)alkylenedioxy 连接到式 I 苯基的相邻碳原子上；Ra 和 R⁵ 独立选自氢、(1-4C)烷基、(1-4C)烷氧基、卤素、三氟甲基、氰基和硝基；A 是亚甲基；X 是亚苯基，任选带有选自 (1-4C)烷基、(1-4C)烷氧基、卤素、三氟甲基、氰基和硝基的取代基，或 X 是相邻苯基与分子 A 之间的直接键；Z 是 1H -四唑-5-基、-CO.NH.（1H-四唑-5-基）或式-CO.OR⁶或-CO.NH.SO₂的基团。其中 R⁷ 是氢或生理上可接受的醇或苯酚的无毒、可生物降解的残留物，R⁷ 是 (1-6C)烷基、(3-8C)环烷基或苯基；其中任何所述苯基可以是未取代的，或带有一个或两个独立选自 (1-4C)烷基、(1-4C)烷氧基、卤代、氰基和三氟甲基的取代基、它们的无毒盐以及包含它们的药物组合物。式 I 化合物具有治疗高血压和充血性心力衰竭等疾病的价值。
• US5444071A
  申请人：——

  公开号：US5444071A

  公开（公告）日：1995-08-22
• New nonpeptide angiotensin II receptor antagonists. 2. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)quinoline derivatives
  作者：Robert H. Bradbury、Christopher P. Allott、Michael Dennis、Eric Fisher、John S. Major、Brian B. Masek、Alec A. Oldham、Robert J. Pearce、Neil Rankine

  DOI：10.1021/jm00100a007

  日期：1992.10

  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.