6-fluoro-7-methoxyquinoxalin-2(1H)-one | 1384067-34-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-fluoro-7-methoxyquinoxalin-2(1H)-one
• 英文别名: 6-fluoro-7-methoxy-1H-quinoxalin-2-one
• CAS: 1384067-34-8
• 化学式: C₉H₇FN₂O₂
• 分子量: 194.165
• InChiKey: LKQZFOIYKAGPDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-fluoro-7-methoxyquinoxalin-2(1H)-one 在 potassium carbonate 、 三溴氧磷 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以54%的产率得到2-bromo-6-fluoro-7-methoxyquinoxaline
  参考文献：
  名称：

  喹喔啉衍生物作为特定的c-Met激酶抑制剂的合成和生物学评估。

  摘要：

  合成了一系列新颖的喹喔啉衍生物，并评估了它们对c-Met激酶的抑制活性。大多数测试的化合物表现出有效的抑制活性。进一步检查了所有合成的喹喔啉类化合物对c-Met过表达的人胃癌细胞系（MKN-45）的抑制作用，该细胞系表现出良好的抑制活性。在合成的化合物中，化合物4在动物模型研究中显示出更好的肿瘤生长抑制作用。我们还确认了其可接受的药物特性和高度选择性的靶标活性。

  DOI：

  10.1016/j.bmcl.2020.127189
• 作为产物：
  描述：

  4-氟-5-甲氧基-2-硝基苯胺 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 乙醇 、 甲苯 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 6-fluoro-7-methoxyquinoxalin-2(1H)-one
  参考文献：
  名称：

  Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa

  摘要：

  Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.

  DOI：

  10.1016/j.bmc.2014.07.040

文献信息

• Optimization of physicochemical properties and safety profile of novel bacterial topoisomerase type II inhibitors (NBTIs) with activity against Pseudomonas aeruginosa
  作者：Folkert Reck、David E. Ehmann、Thomas J. Dougherty、Joseph V. Newman、Sussie Hopkins、Gregory Stone、Nikunj Agrawal、Paul Ciaccio、John McNulty、Herbert Barthlow、Jennifer O’Donnell、Kosalaram Goteti、John Breen、Janelle Comita-Prevoir、Mark Cornebise、Mark Cronin、Charles J. Eyermann、Bolin Geng、Greg R. Carr、Lakshmipathi Pandarinathan、Xuejun Tang、Andrew Cottone、Liang Zhao、Natascha Bezdenejnih-Snyder

  DOI：10.1016/j.bmc.2014.07.040

  日期：2014.10

  Type II bacterial topoisomerases are well validated targets for antimicrobial chemotherapy. Novel bacterial type II topoisomerase inhibitors (NBTIs) of these targets are of interest for the development of new antibacterial agents that are not impacted by target-mediated cross-resistance with fluoroquinolones. We now disclose the optimization of a class of NBTIs towards Gram-negative pathogens, especially against drug-resistant Pseudomonas aeruginosa. Physicochemical properties (pKa and logD) were optimized for activity against P. aeruginosa and for reduced inhibition of the hERG channel. The optimized analogs 9g and 9i displayed potent antibacterial activity against P. aeruginosa, and a significantly improved hERG profile over previously reported analogs. Compound 9g showed an improved QT profile in in vivo models and lower clearance in rat over earlier compounds. The compounds show promise for the development of new antimicrobial agents against drug-resistant Pseudomonas aeruginosa.
• Synthesis and biological evaluation of quinoxaline derivatives as specific c-Met kinase inhibitors
  作者：Seung Chan Kim、Pulla Reddy Boggu、Ha Na Yu、So Young Ki、Jun Min Jung、Yeon Su Kim、Gi Min Park、Sang Ho Ma、In Su Kim、Young Hoon Jung

  DOI：10.1016/j.bmcl.2020.127189

  日期：2020.7

  A series of novel quinoxaline derivatives were synthesized and evaluated for their inhibitory activity against c-Met kinase enzyme. Most of the tested compounds exhibited potent inhibitory activity. All the synthesized quinoxaline compounds were further examined against c-Met overexpressed human gastric cancer cell line (MKN-45), which showed good inhibitory activity. Among the synthesized compounds

  合成了一系列新颖的喹喔啉衍生物，并评估了它们对c-Met激酶的抑制活性。大多数测试的化合物表现出有效的抑制活性。进一步检查了所有合成的喹喔啉类化合物对c-Met过表达的人胃癌细胞系（MKN-45）的抑制作用，该细胞系表现出良好的抑制活性。在合成的化合物中，化合物4在动物模型研究中显示出更好的肿瘤生长抑制作用。我们还确认了其可接受的药物特性和高度选择性的靶标活性。