4-oxo-4-(2,2-dimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-3-methylbutyric acid | 134577-41-6

• 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-(2,2-dimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-3-methylbutyric acid
• 英文别名: 4-(2,2-dimethyl-3-oxo-4H-1,4-benzoxazin-7-yl)-3-methyl-4-oxobutanoic acid
• CAS: 134577-41-6
• 化学式: C₁₅H₁₇NO₅
• 分子量: 291.304
• InChiKey: WIJFMWHMTOHOSD-UHFFFAOYSA-N

物化性质

• 熔点：
  144-150 °C
• 沸点：
  555.8±50.0 °C(predicted)
• 密度：
  1.243±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 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：
  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-(2,2-dimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-3-methylbutyric acid 在 肼 作用下， 以 乙醇 为溶剂， 生成 6-(2,2-dimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-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：

  7-(3-cyano-2-methylpropionyl)-2,2-dimethyl-3,4-dihydro-3-oxo-1,4(2H)benzoxazine 在 盐酸 作用下， 反应 2.0h， 以60%的产率得到4-oxo-4-(2,2-dimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-3-methylbutyric acid
  参考文献：
  名称：

  An Alternative Synthesis of Cardiotonic 6-(3,4-Dihydro-3-OXO-1,4(2H) benzoxazin-7-YL)-2,3,4,5-tetrahydro-5-methylpyridazin-3-ones

  摘要：

  Useful therapeutic 6-(3,4-dihydro-3-oxo-1,4 (2H) benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-ones can be conveniently prepared from 6-propionyl-1,3 benzoxazolin-2-ones using alpha, beta unsaturated ketone as intermediate.

  DOI：

  10.1080/00397919108020821

文献信息

• 6-Benzoxazinylpyridazin-3-ones: potent, long-acting positive inotrope and peripheral vasodilator agents
  作者：Donald W. Combs、Marianne S. Rampulla、Stanley C. Bell、Dieter H. Klaubert、Alfonso J. Tobia、Robert Falotico、Barbara Haertlein、Constance Lakas-Weiss、John B. Moore

  DOI：10.1021/jm00163a061

  日期：1990.1

  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.
• MOUSSAVI, Z.;DEPREUX, P.;LESIEUR, D., SYNTH. COMMUN. , 21,(1991) N, C. 271-278
  作者：MOUSSAVI, Z.、DEPREUX, P.、LESIEUR, D.

  DOI：——

  日期：——
• US5221742A
  申请人：——

  公开号：US5221742A

  公开（公告）日：1993-06-22
• An Alternative Synthesis of Cardiotonic 6-(3,4-Dihydro-3-OXO-1,4(2H) benzoxazin-7-YL)-2,3,4,5-tetrahydro-5-methylpyridazin-3-ones
  作者：Z. Moussavi、P. Depreux、D. Lesieur

  DOI：10.1080/00397919108020821

  日期：1991.1

  Useful therapeutic 6-(3,4-dihydro-3-oxo-1,4 (2H) benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-ones can be conveniently prepared from 6-propionyl-1,3 benzoxazolin-2-ones using alpha, beta unsaturated ketone as intermediate.