(E)-7-fluoro-2-methoxy-8-styryl-1,5-naphthyridine | 881658-51-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-7-fluoro-2-methoxy-8-styryl-1,5-naphthyridine
• 英文别名: trans-7-fluoro-2-methoxy-8-styryl-[1,5]naphthyridine；7-fluoro-2-methoxy-8-[(E)-2-phenylethenyl]-1,5-naphthyridine
• CAS: 881658-51-1
• 化学式: C₁₇H₁₃FN₂O
• 分子量: 280.301
• InChiKey: JZHJYBWJAAFRNA-BQYQJAHWSA-N

物化性质

• 沸点：
  420.3±40.0 °C(Predicted)
• 密度：
  1.265±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 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：

  (E)-7-fluoro-2-methoxy-8-styryl-1,5-naphthyridine 在 potassium osmate(VI) dihydrate 、 sodium periodate 、 甲基磺酰胺 、 N-甲基吗啉氧化物 、 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 二氯甲烷 、 水 、 乙酸乙酯 、 1,2-二氯乙烷 、 叔丁醇 为溶剂， 反应 4.0h， 生成 6-({[(3R,6S)-6-[(1S,2R)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1,2-dihydroxyethyl]oxan-3-yl]amino}methyl)-2H,3H,4H-pyrido[3,2-b][1,4]thiazin-3-one
  参考文献：
  名称：

  Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity

  摘要：

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.

  DOI：

  10.1021/jm400963y
• 作为产物：
  描述：

  8-溴-7-氟-2-甲氧基-1,5-萘啶 、 反式-BETA-苯乙烯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.0h， 以94%的产率得到(E)-7-fluoro-2-methoxy-8-styryl-1,5-naphthyridine
  参考文献：
  名称：

  Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity

  摘要：

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.

  DOI：

  10.1021/jm400963y

文献信息

• Ethanol or 1,2-Ethanediol Cyclohexyl Antibiotic Derivatives
  申请人：Hubschwerlen Christian

  公开号：US20090005368A1

  公开（公告）日：2009-01-01

  The invention relates to antibiotic ethanol or 1,2-ethanediol cyclohexyl derivatives of formula (I) wherein R1 represents (C 1 -C 4 )alkoxy; one or two of U, V, W and X represents) N and the remaining represent each independently CH or, in the case of V or X, may also represent CR a ; R a represents halogen; R 2 represents H or OH; A represents CH 2 , CO, CH 2 CH═CH or COCH═CH; D represents a phenyl group optionally substituted one or two times by halogen atoms, or D represents a group of the formula (II) in which Q is oxygen or sulphur; and to salts of these derivatives of formula (I).

  本发明涉及公式(I)的抗生素乙醇或1,2-乙二醇环己基衍生物，其中R1代表（C1-C4）烷氧基；U、V、W和X中的一个或两个代表N，其余各自独立地代表CH，或在V或X的情况下，也可以代表CRa；Ra代表卤素；R2代表H或OH；A代表CH2、CO、 CH═CH或COCH═CH；D代表苯基，该苯基可以选择地被卤素原子取代一次或两次，或D代表公式（II）中Q为氧或硫的基团；以及公式（I）的这些衍生物的盐。
• Ethanol or 1,2-ethanediol cyclohexyl antibiotic derivatives
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：US07820655B2

  公开（公告）日：2010-10-26

  The invention relates to antibiotic ethanol or 1,2-ethanediol cyclohexyl derivatives of formula (I) wherein R1 represents (C1-C4)alkoxy; one or two of U, V, W and X represents) N and the remaining represent each independently CH or, in the case of V or X, may also represent CRa; Ra represents halogen; R2 represents H or OH; A represents CH2, CO, CH2CH═CH or COCH═CH; D represents a phenyl group optionally substituted one or two times by halogen atoms, or D represents a group of the formula (II) in which Q is oxygen or sulphur; and to salts of these derivatives of formula (I).

  本发明涉及公式（I）的抗生素乙醇或1,2-乙二醇环己基衍生物，其中R1代表（C1-C4）烷氧基; U，V，W和X中的一个或两个代表N，其余各自独立地代表CH，或在V或X的情况下，也可以表示为CRa; Ra代表卤素; R2代表H或OH; A代表CH2，CO， CH═CH或COCH═CH; D代表苯基，该苯基可以选修一次或两次卤素原子，或D代表公式（II）中Q为氧或硫的基团; 以及公式（I）的这些衍生物的盐。
• WO2007/93963
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• WO2007/105154
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• WO2007/86016
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