2-Chloro-6-fluoro-7-methoxyquinoxaline | 1384067-32-6

• 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: 2-Chloro-6-fluoro-7-methoxyquinoxaline
• 英文别名: 2-chloro-6-fluoro-7-methoxyquinoxaline
• CAS: 1384067-32-6
• 化学式: C₉H₆ClFN₂O
• 分子量: 212.611
• InChiKey: DRAYHDDXZOQRLH-UHFFFAOYSA-N

物化性质

• 沸点：
  307.1±37.0 °C(Predicted)
• 密度：
  1.415±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  35
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Chloro-6-fluoro-7-methoxyquinoxaline 在 盐酸 、 偶氮二甲酸二异丙酯 、 水 、 sodium hydride 、 potassium carbonate 、 苯硫酚 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.75h， 生成 trans-2-((4-(2-(6-Fluoro-7-methoxy-2-oxoquinoxalin-1(2H)-yl)-1-(methylamino)ethyl)cyclohexylamino)methyl)-6Hpyrimido[5,4-b][1,4]oxazin-7(8H)-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
• 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， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 2-Chloro-6-fluoro-7-methoxyquinoxaline 、
  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

• [EN] 3,8-DIAZA-BICYCLO[4.2.0]OCT-3-YL AMIDES<br/>[FR] 3,8-DIAZA-BICYCLO[4.2.0]OCT-3-YLAMIDES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2012085857A1

  公开（公告）日：2012-06-28

  The present invention relates to 3,8-diaza-bicyclo[4.2.0]oct-3-yl amide derivatives of formula (I), wherein the relative configuration of the diazabicyclooctane moiety is cis; and wherein Ar1, and Ar2 are as described in the description, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as orexin receptor antagonists.

  本发明涉及式(I)的3,8-二氮杂双环[4.2.0]辛-3-基酰胺衍生物，其中二氮双环辛烷基的相对构型为顺式；以及其中Ar1和Ar2如描述中所述，其制备方法，其药学上可接受的盐，以及作为药物的用途，含有式(I)一个或多个化合物的药物组合物，特别是其用作促进睡眠激素受体拮抗剂。
• 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.