4-(3,4-Dihydro-3-oxo-1,4[2H]-benzothiazin-7-yl)-3-methyl-4-oxobutyric acid | 117259-67-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3,4-Dihydro-3-oxo-1,4[2H]-benzothiazin-7-yl)-3-methyl-4-oxobutyric acid
• 英文别名: 3-methyl-4-oxo-4-(3-oxo-4H-1,4-benzothiazin-7-yl)butanoic acid
• CAS: 117259-67-3
• 化学式: C₁₃H₁₃NO₄S
• 分子量: 279.317
• InChiKey: BEYAEAGBJYXQIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3,4-Dihydro-3-oxo-1,4[2H]-benzothiazin-7-yl)-3-methyl-4-oxobutyric acid 在 肼 作用下， 以 乙醇 为溶剂， 以16%的产率得到6-(3,4-dihydro-3-oxo-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
• 作为产物：
  描述：

  Trimethyl-[2-methyl-3-oxo-3-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-7-yl)-propyl]-ammonium; iodide 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.5h， 生成 4-(3,4-Dihydro-3-oxo-1,4[2H]-benzothiazin-7-yl)-3-methyl-4-oxobutyric acid
  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

• 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。
• US4766118A
  申请人：——

  公开号：US4766118A

  公开（公告）日：1988-08-23
• US5081242A
  申请人：——

  公开号：US5081242A

  公开（公告）日：1992-01-14