6-Propionyl-2H-1,4-benzoxazin-3-on | 26518-85-4

• 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-Propionyl-2H-1,4-benzoxazin-3-on
• 英文别名: 6-propionyl-4H-benzo[1,4]oxazin-3-one；6-propionyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazine；6-propanoyl-4H-1,4-benzoxazin-3-one
• CAS: 26518-85-4
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: SGXMEUBMGXFRJY-UHFFFAOYSA-N

物化性质

• 沸点：
  433.6±45.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Propionyl-2H-1,4-benzoxazin-3-on 在 乙酸酐 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 3.0h， 生成
  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：

  2-氨基苯酚 在 三氯化铝 、 碳酸氢钠 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 6-Propionyl-2H-1,4-benzoxazin-3-on
  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

• Imidazo-heterocyclic compounds and pharmaceutical composition comprising
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04621084A1

  公开（公告）日：1986-11-04

  New imidazo-heterocyclic compounds of the formula: ##STR1## wherein R.sup.1 is hydrogen, lower alkyl or halogen, R.sup.2 is hydrogen, lower alkyl, halogen, aminomethyl optionally substituted with lower alkyl, or piperazin-1-yl-methyl optionally substituted with lower alkyl, R.sup.3 is a partially suturated heterocyclic group selected from benzothiazolinyl, benzoxazolinyl, benzimidazolinyl, 3,4-dihydro-2H-1,4-benzothiazinyl, 3,4-dihydro-2H-1,4-benzoxazinyl and 1,2,3,4-tetrahydroquinoxalinyl, which is substituted with oxo, thioxo, imino or lower alkylimino, and which may be substituted with lower alkyl optionally substituted with lower alkanoyloxy, lower alkoxycarbonyl, pyridyl or lower alkylamino; or an unsaturated heterocyclic group selected from benzoxazolyl and benzimidazolyl, which may be substituted with lower alkyl or pyridyl(lower)alkylthio, and Y is .dbd.N-- or a group of the formula: ##STR2## in which R.sup.4 is hydrogen, hydroxy, lower alkyl, lower alkoxy or ar(lower)alkoxy, and pharmaceutically acceptable salts thereof, and processes for preparation thereof and pharmaceutical composition comprising the same. These derivatives and pharmaceutically acceptable salts thereof are useful as cardiotonic agents and untiulcer agents.

  新的咪唑-杂环化合物的化学式翻译如下：其中R.sup.1为氢、较低的烷基或卤素，R.sup.2为氢、较低的烷基、卤素、氨甲基（可选择性地取代为较低的烷基）或哌嗪-1-基甲基（可选择性地取代为较低的烷基），R.sup.3为从苯并噻唑基、苯并噁唑基、苯并咪唑基、3,4-二氢-2H-1,4-苯并噻唑基、3,4-二氢-2H-1,4-苯并噁唑基和1,2,3,4-四氢喹喔啉基中选择的部分饱和杂环基，该基取代为氧代、硫代、亚胺或较低的烷基亚胺，并且可以取代为可选择性地取代为较低的烷基、可选择性地取代为较低的烷酰氧基、较低的烷氧羰基、吡啶基或较低的烷基氨基；或从苯并噁唑基和苯并咪唑基中选择的不饱和杂环基，该基可以取代为较低的烷基或吡啶基（较低）烷基硫基，Y为.dbd.N--或化学式的一个基团：其中R.sup.4为氢、羟基、较低的烷基、较低的烷氧基或芳基（较低）烷氧基，以及其药学上可接受的盐，以及其制备方法和包含它们的药物组合物。这些衍生物及其药学上可接受的盐可用作心力衰竭药物和抗溃疡药物。
• [EN] CARBOXAMIDE COMPOUNDS AND THEIR USE AS ANTAGONISTS OF THE CHEMOKINE CCR2 RECEPTOR<br/>[FR] COMPOSÉS DE CARBOXYAMIDE ET LEUR UTILISATION COMME ANTAGONISTES DU RÉCEPTEUR CCR2DE LA CHIMIOKINE
  申请人：EPIX DELAWARE INC

  公开号：WO2009076404A1

  公开（公告）日：2009-06-18

  Chemokine receptor antagonists, in particular, compounds of Formula (I) that act as antagonists of the chemokine CCR2 receptor, including pharmaceutical compositions and uses thereof to treat or prevent diseases associated with monocyte accumulation, lymphocyte accumulation or leukocyte accumulation are described; wherein (B/A) is an optionally substituted fused aromatic or partially aromatic bicyclic ring containing at least one nitrogen atom.

  描述了特定的化学物质，即作为趋化因子CCR2受体拮抗剂的Formula (I)化合物，包括其药用组合物和用途，用于治疗或预防与单核细胞、淋巴细胞或白细胞聚积相关的疾病；其中(B/A)是一个可选择地取代的融合芳香或部分芳香的双环环，其中至少含有一个氮原子。
• Carboxamide Compounds and Their Use
  申请人：Ben-Zeev Efrat

  公开号：US20100331298A1

  公开（公告）日：2010-12-30

  Chemokine receptor antagonists, in particular, compounds of Formula (I) that act as antagonists of the chemokine CCR2 receptor, including pharmaceutical compositions and uses thereof to treat or prevent diseases associated with monocyte accumulation, lymphocyte accumulation or leukocyte accumulation are described herein.

  本文描述了化学因子受体拮抗剂，特别是式（I）化合物，其作为趋化因子CCR2受体的拮抗剂，包括制药组合物及其用于治疗或预防与单核细胞聚集、淋巴细胞聚集或白细胞聚集相关的疾病。
• Techer,H. et al., Comptes Rendus des Seances de l'Academie des Sciences, Serie C: Sciences Chimiques, 1970, vol. 270, p. 1601 - 1604
  作者：Techer,H. et al.

  DOI：——

  日期：——
• Imidazo-heterocyclic compounds, processes for preparation thereof and pharmaceutical composition comprising the same
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0120589B1

  公开（公告）日：1988-06-08