6-(2,2,4-trimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one | 114603-34-8

• 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: 6-(2,2,4-trimethyl-3,4-dihydro-3-oxo-1,4-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one
• 英文别名: 2,2,4-trimethyl-7-(4-methyl-6-oxo-4,5-dihydro-1H-pyridazin-3-yl)-1,4-benzoxazin-3-one
• CAS: 114603-34-8
• 化学式: C₁₆H₁₉N₃O₃
• 分子量: 301.345
• InChiKey: MCAMXXSHFLATKY-UHFFFAOYSA-N

物化性质

• 熔点：
  220 °C(Solv: acetone (67-64-1))
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  71
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  7-(3-bromo-2-methylpropionyl)-2,2,4-trimethyl-3,4-dihydro-3-oxo-1,4(2H)benzoxazine 在 盐酸 、 一水合肼 作用下， 以 乙醇 、 水 为溶剂， 反应 9.0h， 生成 6-(2,2,4-trimethyl-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：

  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：——
• US4721784A
  申请人：——

  公开号：US4721784A

  公开（公告）日：1988-01-26
• US5221742A
  申请人：——

  公开号：US5221742A

  公开（公告）日：1993-06-22
• [EN] PROCESS FOR THE PREPARATION OF BENZOXAZINYLTETRAHYDROPYRIDAZINES
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：WO1992011256A1

  公开（公告）日：1992-07-09

  (EN) The invention relates to a process for the synthesis of compounds for formula (I), wherein R1-R5 are as defined. The process is a multistep process which comprises acylating a 2-benzonxazolinone with an alkanoic anhydride to form an acylated carbamate, hydrolyzing the carbamate, reacting the resultant aminophenol with a haloalkanoyl halide to form a substituted benzoxazine, reacting the benzoxazine with an aldehyde, alkylating the resultant aminomethyl compound with an alkylating agent to form a quaternary ammonium salt, reacting the salt with an alkali metal cyanide to form a nitrile, hydrolyzing the nitrile and reacting the resultant carboxylic acid with hydrozine.(FR) L'invention se rapporte à un procédé de synthèse de composés correspondant à la formule (I) dans laquelle R1-R5 sont comme défini. Le procédé est un procédé à étapes multiples comprenant l'acylation d'un 2-benzoxazolinone avec un anhydride alcanoïque pour former un carbamate acylé; l'hydrolyse du carbamate; la réaction de l'aminophénol obtenu avec un halogénure haloalcanoyle pour former une benzoxazine substitué; la réaction de la benzoxazine avec un aldéhyde; l'alkylation du composé aminométhyle obtenu avec un agent d'alkylation pour former un sel d'ammonium quaternaire; la réaction du sel avec un cyanure de métal alcalin pour former un nitrile; l'hydrolyse du nitrile et la réaction de l'acide carboxylique obtenu avec de l'hydrazine.