(4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one | 943025-64-7

• 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: (4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one
• 英文别名: 3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one；5-fluoro-3-hydroxy-3-(hydroxymethyl)-1,7-diazatricyclo[6.3.1.04,12]dodeca-4(12),5,7,9-tetraen-11-one
• CAS: 943025-64-7
• 化学式: C₁₁H₉FN₂O₃
• 分子量: 236.202
• InChiKey: BXJYLIMJPZGRAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  73.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one 在 盐酸 、 二正丁基氧化锡 、 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 22.0h， 生成 (4S)-4-[(4-amino-1-piperidinyl)methyl]-3-fluoro-4-hydroxy-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one
  参考文献：
  名称：

  Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases

  摘要：

  During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.013
• 作为产物：
  描述：

  8-[1-(chloromethyl)ethenyl]-7-fluoro-2-(methyloxy)-1,5-naphthyridine 在 sodium iodide 作用下， 以 水 、 丙酮 、 叔丁醇 为溶剂， 反应 34.0h， 生成 (4R/S)-3-fluoro-4-hydroxy-4-(hydroxymethyl)-4,5-dihydro-7H-pyrrolo[3,2,1-de]-1,5-naphthyridin-7-one
  参考文献：
  名称：

  Novel hydroxyl tricyclics (e.g., GSK966587) as potent inhibitors of bacterial type IIA topoisomerases

  摘要：

  During the course of our research to find novel mode of action antibacterials, we discovered a series of hydroxyl tricyclic compounds that showed good potency against Gram-positive and Gram-negative pathogens. These compounds inhibit bacterial type IIA topoisomerases. Herein we will discuss structure-activity relationships in this series and report advanced studies on compound 1 (GSK966587) which demonstrates good PK and in vivo efficacy properties. X-ray crystallographic studies were used to provide insight into the structural basis for the difference in antibacterial potency between enantiomers. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.07.013

文献信息

• Target-Directed Synthesis of Antibacterial Drug Candidate GSK966587
  作者：Eric A. Voight、Hao Yin、Susan V. Downing、Stacie A. Calad、Hayao Matsuhashi、Ilaria Giordano、Alan J. Hennessy、Richard M. Goodman、Jeffery L. Wood

  DOI：10.1021/ol101235f

  日期：2010.8.6

  An efficient enantioselective total synthesis of the potent antibiotic GSK966587 was accomplished. Highlights of the synthesis include two innovative Heck reactions, a highly selective zincate base directed ortho-metalation, Sharpless asymmetric epoxidation, and a fully convergent final step fragment coupling.

  完成了强效抗生素GSK966587的有效对映选择性全合成。合成的亮点包括两个创新的Heck反应，高选择性的锌酸酯基定向原金属化，Sharpless不对称环氧化和完全收敛的最终步骤片段偶联。
• Heterocyclic Compounds, their Preparation and their Use as Antibacterials
  申请人：Caileau Nathalie

  公开号：US20090036433A1

  公开（公告）日：2009-02-05

  Tricyclic nitrogen containing compounds of formula (I) and their use as antibacterials.

  公式（I）中含有三环氮化合物及其作为抗菌剂的用途。
• COMPOUNDS
  申请人：Cailleau Nathalie

  公开号：US20070185153A1

  公开（公告）日：2007-08-09

  Tricyclic nitrogen containing compounds and their use as antibacterials

  三环氮含化合物及其作为抗菌剂的用途
• HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF TUBERCULOSIS
  申请人：Ballell-Pages Lluis

  公开号：US20100184751A1

  公开（公告）日：2010-07-22

  Tricyclic nitrogen-containing compounds of Formula (I) or pharmaceutically acceptable salts, solvates or N-oxides thereof: compositions containing them, their use in the treatment of tuberculosis, and methods for the preparation of such compounds.

  化合物公式为(I)的三环氮含有化合物或其药学上可接受的盐、溶剂或N-氧化物：包含它们的组合物，它们在结核病治疗中的使用以及制备这些化合物的方法。
• Heterocyclic compounds, their preparation and their use as antibacterials
  申请人：Glaxo Group Limited

  公开号：US07732460B2

  公开（公告）日：2010-06-08

  Tricyclic nitrogen containing compounds of formula (I) and their use as antibacterials.

  公式（I）中含有三环氮化合物及其作为抗菌剂的用途。