methyl (E)-(3'-oxo-3',4'-dihydro-2'H-1',4'-benzoxazin-2'-ylidene)acetate | 106660-13-3

• 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: methyl (E)-(3'-oxo-3',4'-dihydro-2'H-1',4'-benzoxazin-2'-ylidene)acetate
• 英文别名: (E)-methyl 2-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-ylidene)acetate；methyl (2E)-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-ylidene)acetate；methyl (2E)-2-(3-oxo-4H-1,4-benzoxazin-2-ylidene)acetate
• CAS: 106660-13-3
• 化学式: C₁₁H₉NO₄
• 分子量: 219.197
• InChiKey: PSMQHDIICKBXEF-RMKNXTFCSA-N

物化性质

• 沸点：
  411.2±45.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为产物：
  描述：

  2-氨基苯酚 在 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 生成 methyl (E)-(3'-oxo-3',4'-dihydro-2'H-1',4'-benzoxazin-2'-ylidene)acetate
  参考文献：
  名称：

  Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis

  摘要：

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.

  DOI：

  10.1016/j.bmcl.2019.07.025

文献信息

• Teitei, Tsutomu, Australian Journal of Chemistry, 1986, vol. 39, # 3, p. 503 - 510
  作者：Teitei, Tsutomu

  DOI：——

  日期：——
• Design, synthesis and antimycobacterial activity of benzoxazinone derivatives and open-ring analogues: Preliminary data and computational analysis
  作者：Daniele Zampieri、Maria Grazia Mamolo、Julia Filingeri、Sara Fortuna、Alessandro De Logu、Adriana Sanna、Davide Zanon

  DOI：10.1016/j.bmcl.2019.07.025

  日期：2019.9

  This study examines in depth benzoxazine nucleus for antimycobacterial property. We synthesized some benzoxazin-2-one and benzoxazin-3-one derivatives, which were tested for activity against a panel of Mycobacterium tuberculosis (Mtb) strains, including H37Ra, H37Rv and some resistant strains. Several compounds displayed a high antimycobacterial activity and the three isoniazid analogue derivatives 8a-c exhibited a MIC range of 0.125-0.250 mu g/mL (0.37-0.75 mu M) against strain H37Ra, therefore lower than the isoniazid reference drug. Two benzoxazin-2-one derivatives, 1c and 5j, together with isoniazid-analogue compound 8a, also revealed low MIC values against resistant strains and proved highly selective for mycobacterial cells, compared to mammalian Vero cells. To predict whether molecule 8a is able to interact with the active site of InhA, we docked it into the crystal structure; indeed, during the molecular dynamic simulation the compound never left the protein pocket. The more active compounds were predicted for ADME properties and all proved to be potentially orally active in humans.