(E)-6-(3-(3-(5-methoxy-3-methylbenzofuran-2-yl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one | 1621696-91-0

• 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: (E)-6-(3-(3-(5-methoxy-3-methylbenzofuran-2-yl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one
• 英文别名: 6-[(E)-3-[3-(5-methoxy-3-methyl-1-benzofuran-2-yl)azetidin-1-yl]-3-oxoprop-1-enyl]-3,4-dihydro-1H-1,8-naphthyridin-2-one
• CAS: 1621696-91-0
• 化学式: C₂₄H₂₃N₃O₄
• 分子量: 417.464
• InChiKey: NXVFDAYGCZYJAY-FPYGCLRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  84.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-甲氧基-3-甲基苯并呋喃 在 ferrous(II) sulfate heptahydrate 、 硫酸 、 双氧水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (E)-6-(3-(3-(5-methoxy-3-methylbenzofuran-2-yl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one
  参考文献：
  名称：

  Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors

  摘要：

  A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.

  DOI：

  10.1016/j.ejmech.2014.07.036

文献信息

• Discovery of azetidine based ene-amides as potent bacterial enoyl ACP reductase (FabI) inhibitors
  作者：Mohamed Takhi、Kandepu Sreenivas、Chandrashekar K. Reddy、Mahadari Munikumar、Kolakota Praveena、Pabolu Sudheer、Bandaru N.V.M. Rao、Gollamudi Ramakanth、Jampala Sivaranjani、Shardaprasad Mulik、Yeruva R. Reddy、Krishnamurthy Narasimha Rao、Rentala Pallavi、Anirudha Lakshminarasimhan、Sunil K. Panigrahi、Thomas Antony、Iskandar Abdullah、Yean K. Lee、Murali Ramachandra、Rohana Yusof、Noorsaadah A. Rahman、Hosahalli Subramanya

  DOI：10.1016/j.ejmech.2014.07.036

  日期：2014.9

  A novel and potent series of ene-amides featuring azetidines has been developed as FabI inhibitors active against drug resistant Gram-positive pathogens particularly staphylococcal organisms. Most of the compounds from the series possessed excellent biochemical inhibition of Staphylococcus aureus FabI enzyme and whole cell activity against clinically relevant MRSA, MSSA and MRSE organisms which are responsible for significant morbidity and mortality in community as well as hospital settings. The binding mode of one of the leads, AEA16, in Escherichia coli FabI enzyme was determined unambiguously using X-ray crystallography. The lead compounds displayed good metabolic stability in mice liver microsomes and pharmacokinetic profile in mice. The in vivo efficacy of lead AEA16 has been demonstrated in a lethal murine systemic infection model.