trans 3-(3-fluoro-4-methoxyphenyl)-2-propenoic acid methyl ester | 695187-33-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: trans 3-(3-fluoro-4-methoxyphenyl)-2-propenoic acid methyl ester
• 英文别名: methyl (2E)-3-(3-fluoro-4-methoxyphenyl)prop-2-enoate；methyl (E)-3-(3-fluoro-4-methoxyphenyl)prop-2-enoate
• CAS: 695187-33-8
• 化学式: C₁₁H₁₁FO₃
• 分子量: 210.205
• InChiKey: QPCMUWPYFYSMAG-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trans 3-(3-fluoro-4-methoxyphenyl)-2-propenoic acid methyl ester 在 二异丁基氢化铝 作用下， 以 正己烷 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 (E)-3-(3-fluoro-4-methoxyphenyl)prop-2-en-1-ol
  参考文献：
  名称：

  Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections

  摘要：

  Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.090
• 作为产物：
  描述：

  三甲基膦酰基乙酸酯 、 3-氟-4-甲氧基苯甲醛 在 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 trans 3-(3-fluoro-4-methoxyphenyl)-2-propenoic acid methyl ester
  参考文献：
  名称：

  Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections

  摘要：

  Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.12.090

文献信息

• [EN] BENZOXAZOLE, BENZTHIAZOLE AND BENZIMIDAZOLE ACID DERIVATIVES AND THEIR USE AS HEPARANASE INHIBITORS<br/>[FR] DERIVES D'ACIDES DE BENZOXAZOLE, DE BENZOTHIAZOLE, ET DE BENZIMIDAZOLE PHARMACEUTIQUEMENT ACTIFS
  申请人：OXFORD GLYCOSCIENCES UK LTD

  公开号：WO2004046122A2

  公开（公告）日：2004-06-03

  Compounds of formula (I): wherein R1, R2 and R3 are independently, hydrogen, halogen, CF3, OR6, NR7R8, NR8COR10, NR8SO2R10 or C1-6 alkyl optionally substituted by hydroxy, C1-6 alkoxy or NR7R8; R4 is NR8CONR8R9, NR8COR9, NR8SO2R9, or W-CONR8R9, where W is a bond, C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; and R5 is Formula (A) methods for their synthesis, pharmaceutical compositions comprising them and their use in medicine, in particular for the treatment of cancer.
• Discovery of novel piperonyl derivatives as diapophytoene desaturase inhibitors for the treatment of methicillin-, vancomycin- and linezolid-resistant Staphylococcus aureus infections
  作者：Hanwen Wei、Fei Mao、Shuaishuai Ni、Feifei Chen、Baoli Li、Xiaoxia Qiu、Linghao Hu、Manjiong Wang、Xinyu Zheng、Jin Zhu、Lefu Lan、Jian Li

  DOI：10.1016/j.ejmech.2017.12.090

  日期：2018.2

  Inhibition of S. aureus diapophytoene desaturase (CrtN) could serve as an alternative approach for addressing the tricky antibiotic resistance by blocking the biosynthesis of carotenoid pigment which shields the bacterium from host oxidant killing. In this study, we designed and synthesized 44 derivatives with piperonyl scaffold targeting CrtN and the structure-activity relationships (SARs) were examined extensively to bring out the discovery of 21b with potent efficacy and better hERG safety profile compared to the first class CrtN inhibitor benzocycloalkane derivative 2. Except the excellent pigment inhibitory activity against wild-type S. aureus, 21b also showed excellent pigment inhibition against four pigmented MRSA strains. In addition, H2O2 killing and human whole blood killing assays proved 21b could sensitize S. aureus to be killed under oxidative stress conditions. Notably, the murine study in vivo validated the efficacy of 21b against pigmented S. aureus Newman, vancomycin-intermediate S. aureus Mu50 and linezolid-resistant S. aureus NRS271. (C) 2018 Elsevier Masson SAS. All rights reserved.