2-Methylsulfanyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one | 207744-02-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-Methylsulfanyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one
• 英文别名: 2-methylsulfanyl-5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d][1,3]oxazin-4-one
• CAS: 207744-02-3
• 化学式: C₁₁H₁₁NO₂S₂
• 分子量: 253.346
• InChiKey: YFVZFQLKGOVOTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  92.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-Methylsulfanyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one 在 3-(环己胺)-1-丙磺酸 作用下， 以 二甲基亚砜 为溶剂， 生成 2-Methylsulfanylcarbonylamino-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxylic acid
  参考文献：
  名称：

  Novel Thieno[2,3-d][1,3]oxazin-4-ones as Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with K-i values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.

  DOI：

  10.1021/jm9708341
• 作为产物：
  描述：

  tert-butyl 2-isothiocyanato-4,5,6,7-tetrahydrobenzo[b]-thiophene-3-carboxylate 在 sodium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 6.03h， 生成 2-Methylsulfanyl-5,6,7,8-tetrahydro-benzo[4,5]thieno[2,3-d][1,3]oxazin-4-one
  参考文献：
  名称：

  Novel Thieno[2,3-d][1,3]oxazin-4-ones as Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with K-i values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.

  DOI：

  10.1021/jm9708341

文献信息

• Novel Thieno[2,3-<i>d</i>][1,3]oxazin-4-ones as Inhibitors of Human Leukocyte Elastase
  作者：Michael Gütschow、Ulf Neumann

  DOI：10.1021/jm9708341

  日期：1998.5.1

  A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with K-i values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.

表征谱图