4-oxo-4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-methylbutanoic acid | 71008-65-6

• 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: 4-oxo-4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-methylbutanoic acid
• 英文别名: 3-methyl-4-(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)-4-oxobutanoic acid
• CAS: 71008-65-6
• 化学式: C₁₅H₁₇NO₄
• 分子量: 275.304
• InChiKey: IUGFOSCYDTUTBV-UHFFFAOYSA-N

物化性质

• 沸点：
  604.4±55.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-oxo-4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-methylbutanoic acid 在 一水合肼 作用下， 以 乙醇 为溶剂， 生成 3,4-二氢-1-甲基-6-(1,4,5,6-四氢-4-甲基-6-氧代-3-哒嗪基)-2(1H)-喹啉酮
  参考文献：
  名称：

  Dihydropyridazinone cardiotonics. The discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one

  摘要：

  We discovered that 6 (N-[4-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)phenyl]acetamide) is a potent positive inotrope in dogs, and we have prepared several lactam analogues of this agent. These included 16 (1,3-dihydro-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one), 32 (the analogous quinolin-2-one), and 37 (the analogous benzazepin-2-one). The inotropic ED50's of these compounds were 24, 3.3, and 5.2 micrograms/kg, respectively, after iv administration to pentobarbital-anesthetized dogs. Compound 20 (LY195115, 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-i ndol-2- one), the geminal dimethyl analogue of 16, was 3.5-fold more potent than 16 when administered iv (ED50 = 6.8 micrograms/kg). However, the most profound effect of the geminal alkyl substitution was on oral activity. The approximate ED50's of 20 and 16 after oral administration to conscious dogs were 25 and 400 micrograms/kg, respectively. The increase in contractility produced by 25 micrograms/kg of 20 was maximally sustained in excess of 8 h. Thus, 20 is one of the most potent and long-acting oral inotropes described to date.

  DOI：

  10.1021/jm00160a006
• 作为产物：
  描述：

  benzyl 4-((2-hydroxyethyl)carbamoyl)piperidine-1-carboxylate 在 盐酸 作用下， 反应 2.0h， 生成 4-oxo-4-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)-3-methylbutanoic acid
  参考文献：
  名称：

  Dihydropyridazinone cardiotonics. The discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one

  摘要：

  We discovered that 6 (N-[4-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)phenyl]acetamide) is a potent positive inotrope in dogs, and we have prepared several lactam analogues of this agent. These included 16 (1,3-dihydro-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one), 32 (the analogous quinolin-2-one), and 37 (the analogous benzazepin-2-one). The inotropic ED50's of these compounds were 24, 3.3, and 5.2 micrograms/kg, respectively, after iv administration to pentobarbital-anesthetized dogs. Compound 20 (LY195115, 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-i ndol-2- one), the geminal dimethyl analogue of 16, was 3.5-fold more potent than 16 when administered iv (ED50 = 6.8 micrograms/kg). However, the most profound effect of the geminal alkyl substitution was on oral activity. The approximate ED50's of 20 and 16 after oral administration to conscious dogs were 25 and 400 micrograms/kg, respectively. The increase in contractility produced by 25 micrograms/kg of 20 was maximally sustained in excess of 8 h. Thus, 20 is one of the most potent and long-acting oral inotropes described to date.

  DOI：

  10.1021/jm00160a006

文献信息

• Pyridazinone compounds
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：US04258185A1

  公开（公告）日：1981-03-24

  Pyridazinone compounds of the formula: ##STR1## wherein A, B, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are as defined hereinafter, and pharmaceutically acceptable acid addition salts thereof are disclosed. They are useful as antithrombotic and antihypertensive drugs.

  Pyridazinone化合物的化学式为：##STR1## 其中A、B、R.sup.1、R.sup.2、R.sup.3、R.sup.4和R.sup.5的定义如下，以及其药学上可接受的酸盐也被披露。它们可用作抗血栓和降压药物。
• HAKAO, ITARU;SEHTOGUTI, SINRO;YAOKA, OSAMU
  作者：HAKAO, ITARU、SEHTOGUTI, SINRO、YAOKA, OSAMU

  DOI：——

  日期：——
• US4258185A
  申请人：——

  公开号：US4258185A

  公开（公告）日：1981-03-24
• Dihydropyridazinone cardiotonics. The discovery and inotropic activity of 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one
  作者：David W. Robertson、Joseph H. Krushinski、E. E. Beedle、V. Wyss、G. Don Pollock、Harve Wilson、Raymond F. Kauffman、J. Scott Hayes

  DOI：10.1021/jm00160a006

  日期：1986.10

  We discovered that 6 (N-[4-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)phenyl]acetamide) is a potent positive inotrope in dogs, and we have prepared several lactam analogues of this agent. These included 16 (1,3-dihydro-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-indol-2-one), 32 (the analogous quinolin-2-one), and 37 (the analogous benzazepin-2-one). The inotropic ED50's of these compounds were 24, 3.3, and 5.2 micrograms/kg, respectively, after iv administration to pentobarbital-anesthetized dogs. Compound 20 (LY195115, 1,3-dihydro-3,3-dimethyl-5-(1,4,5,6-tetrahydro-6-oxo-3-pyridazinyl)-2H-i ndol-2- one), the geminal dimethyl analogue of 16, was 3.5-fold more potent than 16 when administered iv (ED50 = 6.8 micrograms/kg). However, the most profound effect of the geminal alkyl substitution was on oral activity. The approximate ED50's of 20 and 16 after oral administration to conscious dogs were 25 and 400 micrograms/kg, respectively. The increase in contractility produced by 25 micrograms/kg of 20 was maximally sustained in excess of 8 h. Thus, 20 is one of the most potent and long-acting oral inotropes described to date.