(E)-6-(3-(3-(3-methylbenzofuran-2-yl)azetidin-1-yl)-3-oxoprop-1-en-1-yl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one | 1309206-57-2

• 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-(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: (E)-6-(3-(3-(3-methylbenzofuran-2-yl)azetidin-1-yl)-3-oxoprop-1-enyl)-3,4-dihydro-1,8-naphthyridin-2(1H)-one；6-[(E)-3-[3-(3-methyl-1-benzofuran-2-yl)azetidin-1-yl]-3-oxoprop-1-enyl]-3,4-dihydro-1H-1,8-naphthyridin-2-one
• CAS: 1309206-57-2
• 化学式: C₂₃H₂₁N₃O₃
• 分子量: 387.438
• InChiKey: OTHXOQIDEXDBSX-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  75.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基烟酸 在 palladium diacetate lithium aluminium tetrahydride 、 N-羟基-7-氮杂苯并三氮唑 、 氢溴酸 、 溴 、 sodium methylate 、 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 、 三(邻甲基苯基)磷 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丙腈 为溶剂， 反应 26.92h， 生成 (E)-6-(3-(3-(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：

  [EN] NOVEL HETEROCYCLIC ACRYLAMIDES AND THEIR USE AS PHARMACEUTICALS
  [FR] NOUVEAUX ACRYLAMIDES HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QUE PRODUITS PHARMACEUTIQUES

  摘要：

  这项发明涉及新颖的杂环丙烯酰胺化合物（I），涉及该化合物及其中间体的制备，涉及将该化合物用作抗菌药物以及含有该化合物的药物组合物的用途。

  公开号：

  WO2011061214A1

文献信息

• [EN] ANTIBIOTICS EFFECTIVE FOR GRAM-NEGATIVE PATHOGENS<br/>[FR] ANTIBIOTIQUES EFFICACES CONTRE LES PATHOGÈNES GRAM-NÉGATIFS
  申请人：UNIV ILLINOIS

  公开号：WO2019177975A1

  公开（公告）日：2019-09-19

  Disclosed herein are antibacterial compounds that accumulate in Gram-negative bacteria, methods of preparing the compounds, and methods of using the compounds to inhibit or kill microbes, and methods of treating microbial infections, such as Gram-negative bacterial infections. Compounds selected for conversion to potential Gram-negative antibacterial compounds were identified based on compounds having low globularity and low flexibility. Amine substituents were then strategically added to the selected compounds to provide compounds having antibacterial activity against Gram-negative bacteria.

  本文披露了在革兰氏阴性细菌中积累的抗菌化合物，制备这些化合物的方法，以及利用这些化合物抑制或杀灭微生物，以及治疗微生物感染的方法，如革兰氏阴性细菌感染。选择用于转化为潜在革兰氏阴性抗菌化合物的化合物是基于具有低球形度和低柔性的化合物。然后在所选的化合物中策略性地添加氨基取代基，以提供对革兰氏阴性细菌具有抗菌活性的化合物。
• NOVEL HETEROCYCLIC ACRYLAMIDES AND THEIR USE AS PHARMACEUTICALS
  申请人：Gerusz Vincent

  公开号：US20120277207A1

  公开（公告）日：2012-11-01

  The invention relates to novel heterocyclic acrylamide compounds (I), to the preparation of the compounds and intermediates used therein, to the use of the compounds as antibacterial medicaments and pharmaceutical compositions containing the compounds.

  本发明涉及新型杂环丙烯酰胺化合物（I），以及制备该化合物和其中所使用的中间体，将该化合物用作抗菌药物以及含有该化合物的制药组合物。
• Heterocyclic acrylamides and their use as pharmaceuticals
  申请人：FAB PHARMA S.A.S

  公开号：US09051321B2

  公开（公告）日：2015-06-09

  The invention relates to novel heterocyclic acrylamide compounds (I), to the preparation of the compounds and intermediates used therein, to the use of the compounds as antibacterial medicaments and pharmaceutical compositions containing the compounds.

  本发明涉及新型杂环丙烯酰胺化合物（I），以及制备该化合物和其中间体的方法，将该化合物作为抗菌药物和含有该化合物的药物组合物。
• [EN] FABI INHIBITORS FOR GRAM-NEGATIVE PATHOGENS<br/>[FR] INHIBITEURS DE FABI POUR DES PATHOGÈNES À GRAM NÉGATIF
  申请人：UNIV ILLINOIS

  公开号：WO2022187329A1

  公开（公告）日：2022-09-09

  A FabI inhibitor called fabimycin that has impressive activity against >200 clinical isolates ofE. coli,K. pneumoniae, andA. baumannii. Fabimycin has activity in multiple mouse models of infection caused by Gram-negative bacteria, including a model of urinary tract infection. Fabimycin has translational promise, and its discovery provides data indicating that antibiotics whose spectrum of activity is restricted to Gram-positive bacteria can be systematically modified to accumulate in Gram-negative bacteria and be effective against these problematic pathogens.

  一种名为Fabimycin的FabI抑制剂对200多种临床分离的E. coli、K. pneumoniae和A. baumannii表现出令人印象深刻的活性。Fabimycin在多个小鼠感染模型中对革兰氏阴性菌引起的感染具有活性，包括尿路感染模型。Fabimycin具有翻译前景，其发现提供了数据，表明其谱系活性仅限于革兰氏阳性菌的抗生素可以被系统地改变以在革兰氏阴性菌中积累并对这些问题菌产生作用。
• 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.