methyl 2-[2-oxo-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ylidene]acetate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl 2-[2-oxo-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ylidene]acetate
• 英文别名: (Z)-methyl 2-(2-oxo-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ylidene)acetate；(Z)-3-methoxycarbonylmethylene-3,4-dihydro-2H-5-aza-1,4-benzoxazin-2-one；methyl (2Z)-2-(2-oxo-4H-pyrido[3,2-b][1,4]oxazin-3-ylidene)acetate
• 化学式: C₁₀H₈N₂O₄
• 分子量: 220.185
• InChiKey: AAONBIOIZZKLJN-WAYWQWQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  77.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氨基-3-羟基吡啶 、 丁炔二酸二甲酯 反应 0.07h， 以98%的产率得到methyl 2-[2-oxo-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-ylidene]acetate
  参考文献：
  名称：

  Introduction of a clean and promising protocol for the synthesis of β-amino-acrylates and 1,4-benzoheterocycles: an emerging innovation

  摘要：

  提出了一种高效、优雅且简单的过程，用于合成β-氨基丙烯酸酯衍生物和一系列具有生物学及药物活性的苯并杂环化合物，条件极为温和。该方案为已知方法提供了一种有价值的替代方案，并将应用于绿色合成领域。产品的区域和立体化学性质通过红外光谱、核磁共振和单晶X射线分析得以确定。

  DOI：

  10.1039/c1gc15701a

文献信息

• Introduction of a clean and promising protocol for the synthesis of β-amino-acrylates and 1,4-benzoheterocycles: an emerging innovation
  作者：Garima Choudhary、Rama Krishna Peddinti

  DOI：10.1039/c1gc15701a

  日期：——

  A highly efficient, elegant and simple procedure with exceptionally mild conditions has been proposed for the synthesis of β-amino-acrylate derivatives and an array of biologically and pharmaceutically active benzoheterocycles. The protocol offers a valuable alternative to known methods and will find applications in the field of green synthesis. The regio- and stereo-chemistry of the products were established by IR, NMR and single crystal X-ray analysis.

  提出了一种高效、优雅且简单的过程，用于合成β-氨基丙烯酸酯衍生物和一系列具有生物学及药物活性的苯并杂环化合物，条件极为温和。该方案为已知方法提供了一种有价值的替代方案，并将应用于绿色合成领域。产品的区域和立体化学性质通过红外光谱、核磁共振和单晶X射线分析得以确定。
• Vinyltriphenylphosphonium salt mediated synthesis of 1,4-benzoxazine and coumarin derivatives
  作者：Issa Yavari、Mehdi Adib、Leila Hojabri

  DOI：10.1016/s0040-4020(02)00758-5

  日期：2002.8

  Protonation of the reactive 1:1 intermediate produced in the reaction between triphenylphosphine and dimethyl acetylenedicarboxylate by 2-aminophenol, 3-aminophenol, 4-aminophenol and 2-amino-3-hydroxypyridine leads to vinyltriphenylphosphonium salts, which undergo Michael addition with the conjugate base of the aminophenol or aminohydroxypyridine to produce highly functionalized heterocyclic compounds. (C) 2002 Elsevier Science Ltd. All rights reserved.
• 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.