6-(3,4-dihydro-1,1,3-trioxo-2H-1,4-benzothiazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one | 136912-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 6-(3,4-dihydro-1,1,3-trioxo-2H-1,4-benzothiazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one
• 英文别名: 4-methyl-1,1-dioxo-7-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)-1lambda6,4-benzothiazin-3-one；4-methyl-1,1-dioxo-7-(6-oxo-4,5-dihydro-1H-pyridazin-3-yl)-1λ6,4-benzothiazin-3-one
• CAS: 136912-50-0
• 化学式: C₁₃H₁₃N₃O₄S
• 分子量: 307.33
• InChiKey: UGLRHAYAQBTIDR-UHFFFAOYSA-N

物化性质

• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-(4-氨基苯基)-4-氧代丁酸乙酯 在 sodium sulfide 、 溴 、 sodium hydride 、 potassium carbonate 、 间氯过氧苯甲酸 、 肼 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 5.08h， 生成 6-(3,4-dihydro-1,1,3-trioxo-2H-1,4-benzothiazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one
  参考文献：
  名称：

  Heteroatom analogs of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones

  摘要：

  A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.

  DOI：

  10.1021/jm00079a023

文献信息

• Heteroatom analogs of bemoradan: chemistry and cardiotonic activity of 1,4-benzothiazinylpyridazinones
  作者：Donald W. Combs、Marianne S. Rampulla、James P. Demers、Robert Falotico、John B. Moore

  DOI：10.1021/jm00079a023

  日期：1992.1

  A series of close analogues of the potent, long-acting cardiotonic bemoradan (2a) was synthesized and examined in both in vitro and in vivo test systems. Changing the oxygen heteroatom at the 1-position of the benzoxazine ring of bemoradan to sulfur gave 4a, a more potent enzyme inhibitor and in vivo cardiotonic compound by the iv route. Intraduodenal administration of bemoradan, however, showed a superior response compared to its sulfur analogue, possibly due to oxidation of sulfur followed by a facile Pummerer rearrangement. Model studies were performed to examine the effect of the oxidation state of sulfur. Lack of a heteroatom at the 1-position, 3a (Y-590), afforded a compound with activity and potency very similar to those of bemoradan while the 1-selena compound gave a much less potent analogue 5. Analogues having a methyl group on the 4-nitrogen (2b, 3b, and 4b) were less potent than the desmethyl compounds, but all of these compounds have potent PDE III inhibiting activity and the ability to increase cardiac force in an anesthetized dog preparation when given iv.