2-Diethylamino-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one | 257611-24-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 2-Diethylamino-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one
• 英文别名: 2-(diethylamino)-[1]benzothiolo[2,3-d][1,3]oxazin-4-one
• CAS: 257611-24-8
• 化学式: C₁₄H₁₄N₂O₂S
• 分子量: 274.343
• InChiKey: VBBIMBAKXRTSNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  70.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-苯并[B]噻吩-3-羧酸乙酯 在 sodium hydroxide 、 PPA 、 calcium carbonate 、 mercury(II) oxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 56.33h， 生成 2-Diethylamino-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one
  参考文献：
  名称：

  2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.

  DOI：

  10.1021/jm991108w

文献信息

• 2-(Diethylamino)thieno[1,3]oxazin-4-ones as Stable Inhibitors of Human Leukocyte Elastase
  作者：Michael Gütschow、Lars Kuerschner、Ulf Neumann、Markus Pietsch、Reik Löser、Norman Koglin、Kurt Eger

  DOI：10.1021/jm991108w

  日期：1999.12.1

  A series of 2-(diethylamino)thieno[1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno[2,3-d][1,3]oxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno[2,3-d] and thieno[3,2-d] fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-[1]benzothieno[2,3-d][1,3]oxazin-4-one, exhibited a K-i value of 5.8 nM. 2-(Diethylamino)thieno[1,3]oxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.