(Z)-methyl 2-(7-chloro-2-oxo-2H-benzo[b][1,4]oxazin-3(4H)-ylidene)acetate | 104827-35-2

• 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: (Z)-methyl 2-(7-chloro-2-oxo-2H-benzo[b][1,4]oxazin-3(4H)-ylidene)acetate
• 英文别名: (Z)-3-methoxycarbonylmethylene-7-chloro-3,4-dihydro-2H-1,4-benzoxazin-2-one；Methyl-(7-chloro-2-oxo-2H-1,4-benzoxazin-3(4H)-ylidene)ethanoate；methyl (2Z)-2-(7-chloro-2-oxo-4H-1,4-benzoxazin-3-ylidene)acetate
• CAS: 104827-35-2
• 化学式: C₁₁H₈ClNO₄
• 分子量: 253.642
• InChiKey: CJBPPRMVYLDKJM-YVMONPNESA-N

物化性质

• 熔点：
  172-173 °C
• 沸点：
  397.1±42.0 °C(Predicted)
• 密度：
  1.500±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 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：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-methyl 2-(7-chloro-2-oxo-2H-benzo[b][1,4]oxazin-3(4H)-ylidene)acetate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.25h， 生成 methyl (Z)-2-(7-chloro-2-(pyrrolidin-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-ylidene)acetate
  参考文献：
  名称：

  Expedient synthesis of novel 1,4-benzoxazine and butenolide derivatives

  摘要：

  已开发出一种快速高效的合成2-羟基-1,4-苯并噁嗪衍生物的方案。这些中间体作为合成一系列新型丁烯内酯衍生物和2-氨基-1,4-苯并噁嗪衍生物的前体。

  DOI：

  10.1039/c4ra01736f
• 作为产物：
  描述：

  2-氨基-5-氯苯酚 、 丁炔二酸二甲酯 反应 0.07h， 以98%的产率得到(Z)-methyl 2-(7-chloro-2-oxo-2H-benzo[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

• 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.
• Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: Novel antibacterial agents against Mycobacterium tuberculosis
  作者：Xiaokai Li、Nina Liu、Huaning Zhang、Susan E. Knudson、Richard A. Slayden、Peter J. Tonge

  DOI：10.1016/j.bmcl.2010.08.076

  日期：2010.11

  Menaquinone is an essential component of the electron transport chain in many pathogens and consequently enzymes in the menaquinone biosynthesis pathway are potential drug targets for the development of novel antibacterial agents. In order to identify leads that target MenB, the 1,4-dihydroxy-2-naphthoyl-CoA synthase from Mycobacterium tuberculosis, a high-throughput screen was performed. Several 1,4-benzoxazines were identified in this screen and subsequent SAR studies resulted in the discovery of compounds with excellent antibacterial activity against M. tuberculosis H37Rv with MIC values as low as 0.6 mu g/ml. The 1,4-benzoxazine scaffold is thus a promising foundation for the development of antitubercular agents. (C) 2010 Elsevier Ltd. All rights reserved.