4-oxo-4-<3,4-dihydro-7-methyl-3-oxo-1,4(2H)-benzoxazin-6-yl>-3-methylbutyric acid | 114603-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-oxo-4-<3,4-dihydro-7-methyl-3-oxo-1,4(2H)-benzoxazin-6-yl>-3-methylbutyric acid
• 英文别名: 4-Oxo-4-(3,4-dihydro-7-methyl-3-oxo-1,4(2H)-benzoxazin-6-yl)-3-methylbutyric acid；3-methyl-4-(7-methyl-3-oxo-4H-1,4-benzoxazin-6-yl)-4-oxobutanoic acid
• CAS: 114603-57-5
• 化学式: C₁₄H₁₅NO₅
• 分子量: 277.277
• InChiKey: MPFONOWOTZIVRL-UHFFFAOYSA-N

物化性质

• 沸点：
  577.8±50.0 °C(predicted)
• 密度：
  1.306±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：
  0.36
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-oxo-4-<3,4-dihydro-7-methyl-3-oxo-1,4(2H)-benzoxazin-6-yl>-3-methylbutyric acid 在 肼 作用下， 以 乙醇 为溶剂， 生成 7-methyl-6-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)-4H-1,4-benzoxazin-3-one
  参考文献：
  名称：

  6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents

  摘要：

  A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely potent and selective inhibitor of canine PDE fraction III and a long-acting, potent, orally active inotropic vasodilator agent in various canine models. Additional benzoxazin-6-yl and -8-yl compounds were also prepared. Altering the pyridazinone substitution from the 6-position to the 7-position produced a 14-fold increase in the iv cardiotonic potency (ED50) from 77 to 5.4 micrograms/kg while substitution at the 8-position reduced potency. Methyl substitution at various sites in the molecule was also examined. Positive inotropic activity was maintained for between 8 and 24 h after a single oral dose (100 micrograms/kg) of bemoradan in dogs, thus making it one of the most potent and long-acting orally effective inotropes yet described. Bemoradan is currently under development as a cardiotonic agent for use in the management of congestive heart failure.

  DOI：

  10.1021/jm00163a061
• 作为产物：
  描述：

  3-Methyl-4-(7-methyl-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-4-oxo-butyronitrile 在 盐酸 作用下， 反应 1.5h， 生成 4-oxo-4-<3,4-dihydro-7-methyl-3-oxo-1,4(2H)-benzoxazin-6-yl>-3-methylbutyric acid
  参考文献：
  名称：

  6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents

  摘要：

  A series of 6-benzoxazinylpyridazin-3-ones was prepared and evaluated for inhibition of cardiac phosphodiesterase (PDE) fraction III in vitro and for positive inotropic activity in vivo. 6-[3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl]-2,3,4,5-tetrahydro-5 - methylpyridazin-3-one (bemoradan) was found to be an extremely potent and selective inhibitor of canine PDE fraction III and a long-acting, potent, orally active inotropic vasodilator agent in various canine models. Additional benzoxazin-6-yl and -8-yl compounds were also prepared. Altering the pyridazinone substitution from the 6-position to the 7-position produced a 14-fold increase in the iv cardiotonic potency (ED50) from 77 to 5.4 micrograms/kg while substitution at the 8-position reduced potency. Methyl substitution at various sites in the molecule was also examined. Positive inotropic activity was maintained for between 8 and 24 h after a single oral dose (100 micrograms/kg) of bemoradan in dogs, thus making it one of the most potent and long-acting orally effective inotropes yet described. Bemoradan is currently under development as a cardiotonic agent for use in the management of congestive heart failure.

  DOI：

  10.1021/jm00163a061

文献信息

• 6-benzoxazinyl-2,3,4,5-tetrahydropyridazin-3-ones
  申请人：Ortho Pharmaceutical Corporation

  公开号：US04721784A1

  公开（公告）日：1988-01-26

  The synthesis of benzoxazinyl-pyridazinone compounds is described. The novel compounds are cardiotonic agents and inhibitors of phosphodiesterase fraction III. In addition, the compounds are useful as smooth muscle relaxants and bronchodilators.

  本文描述了苯并噁唑基吡啶酮化合物的合成。这些新型化合物是心脏强心剂和磷酸二酯酶III的抑制剂。此外，这些化合物还可用作平滑肌松弛剂和支气管扩张剂。
• 6-benzoxazinyl- and 6-benzothiazinyl-2,3,4,5-tetrahydropyridazin-3-ones
  申请人：Ortho Pharmaceutical Corporation

  公开号：US04766118A1

  公开（公告）日：1988-08-23

  The synthesis of benzoxazinyl- and benzothiazinylpyridazinone compounds is described. The novel compounds are cardiotonic agents and inhibitors of phosphodiesterase. In addition, the compounds are useful as smooth muscle relaxants and bronchodilators.

  介绍了苯并噁嗪基和苯并噻嗪基吡啶酮化合物的合成。这些新型化合物是心脏强心剂和磷酸二酯酶抑制剂。此外，这些化合物还可用作平滑肌松弛剂和支气管扩张剂。
• 6-benzoxazinyl- and 6-benzothiazinyl 2,3,4,5-tetrahydropyridazin-3-ones
  申请人：Ortho Pharmaceutical Corporation

  公开号：US05081242A1

  公开（公告）日：1992-01-14

  The synthesis of benzoxazinyl- and benzothiazinylpyridazinone compounds is described. The novel compounds are cardiotonic agents and inhibitors of phosphodiesterase. In addition, the compounds are useful as smooth muscle relaxants and bronchodilators.

  本文描述了苯并噁唑基和苯并噻唑基吡啶二酮化合物的合成。这些新化合物是心脏强效剂和磷酸二酯酶抑制剂。此外，这些化合物还可用作平滑肌松弛剂和支气管扩张剂。
• 6-Benzoxazinyl- and 6-benzothiazinyl-2,3,4,5-tetrahydropyridazin-3-ones
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：EP0272914A2

  公开（公告）日：1988-06-29

  The synthesis of benzoxazinyl- and benzothiazinylpyridazinone compounds is described. The novel compounds are cardiotonic agents and inhibitors of phosphodiesterase. In addition, the compounds are useful as smooth muscle relaxants and bronchodilators.

  介绍了苯并恶嗪基和苯并噻嗪基哒嗪酮化合物的合成。 这些新型化合物是强心剂和磷酸二酯酶抑制剂。 此外，这些化合物还可用作平滑肌松弛剂和支气管扩张剂。
• COMBS, DONALD W.
  作者：COMBS, DONALD W.

  DOI：——

  日期：——