1-(2,4-dimethoxybenzyl)-6-fluoro-4-oxo-7-pyrrolidin-1-yl-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid | 779337-66-5

• 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: 1-(2,4-dimethoxybenzyl)-6-fluoro-4-oxo-7-pyrrolidin-1-yl-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid
• 英文别名: 1-[(2,4-dimethoxyphenyl)methyl]-6-fluoro-4-oxo-7-pyrrolidin-1-yl-1,8-naphthyridine-3-carboxylic acid
• CAS: 779337-66-5
• 化学式: C₂₂H₂₂FN₃O₅
• 分子量: 427.432
• InChiKey: GWNCZIDMJLNODI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  92.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-(2,4-dimethoxybenzyl)-6-fluoro-4-oxo-7-pyrrolidin-1-yl-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid 在 二异丁基氢化铝 、 sodium cyanoborohydride 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 为溶剂， 生成 1-(2,4-Dimethoxy-benzyl)-6-fluoro-3-phenylaminomethyl-7-pyrrolidin-1-yl-1H-[1,8]naphthyridin-4-one
  参考文献：
  名称：

  Novel inhibitors of bacterial protein synthesis: structure–activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants

  摘要：

  Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.091
• 作为产物：
  描述：

  2,6-dichloro-α-(ethoxymethylene)-5-fluoro-β-oxo-3-pyridinepropanoic acid ethyl ester 在 lithium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 35.0h， 生成 1-(2,4-dimethoxybenzyl)-6-fluoro-4-oxo-7-pyrrolidin-1-yl-1,4-dihydro-1,8-naphthyridine-3-carboxylic Acid
  参考文献：
  名称：

  Novel inhibitors of bacterial protein synthesis: structure–activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants

  摘要：

  Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.091

文献信息

• Antibacterial compounds
  申请人：——

  公开号：US20030232818A1

  公开（公告）日：2003-12-18

  Antibacterials having formula (I) 1 and salts, prodrugs, and salts of prodrugs thereof, processes for making the compounds and intermediates used in the processes, compositions containing the compounds, and methods of prophylaxis and treatment of bacterial infections using the compounds are disclosed.

  抗菌剂的化学式（I）及其盐、前药、前药的盐，制备这些化合物的方法和用于制备过程中使用的中间体，含有这些化合物的组合物，以及使用这些化合物进行细菌感染的预防和治疗方法被披露。
• Novel Antibacterial Class:  A Series of Tetracyclic Derivatives
  作者：Mira M. Hinman、Teresa A. Rosenberg、Darlene Balli、Candace Black-Schaefer、Linda E. Chovan、Douglas Kalvin、Philip J. Merta、Angela M. Nilius、Steve D. Pratt、Niru B. Soni、Frank L. Wagenaar、Moshe Weitzberg、Rolf Wagner、Bruce A. Beutel

  DOI：10.1021/jm060010w

  日期：2006.8.1

  We describe the synthesis and antibacterial activity of a series of tetracyclic naphthyridones. The members of this series act primarily via inhibition of bacterial translation and belong to the class of novel ribosome inhibitors (NRIs). In this paper we explore the structure-activity relationships (SAR) of these compounds to measure their ability both to inhibit bacterial translation and also to inhibit the growth of bacterial cells in culture. The most active of these compounds inhibit Streptococcus pneumoniae translation at concentrations of < 5 mu M and have minimum inhibitory concentrations (MICs) of < 8 mu g/mL against clinically relevant strains of bacteria.
• US8163769B2
  申请人：——

  公开号：US8163769B2

  公开（公告）日：2012-04-24
• Novel inhibitors of bacterial protein synthesis: structure–activity relationships for 1,8-naphthyridine derivatives incorporating position 3 and 4 variants
  作者：Richard F. Clark、Sanyi Wang、Zhenkun Ma、Moshe Weitzberg、Christopher Motter、Michael Tufano、Rolf Wagner、Yu-Gui Gu、Peter J. Dandliker、Claude G. Lerner、Linda E. Chovan、Yingna Cai、Candace L. Black-Schaefer、Linda Lynch、Douglas Kalvin、Angela M. Nilius、Steve D. Pratt、Niru Soni、Tianyuan Zhang、Xiaolin Zhang、Bruce A. Beutel

  DOI：10.1016/j.bmcl.2004.03.091

  日期：2004.6

  Structure-activity relationships for a recently discovered novel ribosome inhibitor (NRI) class of antibacterials were investigated. Preliminary efforts to optimize protein synthesis inhibitory activity of the series through modification of positions 3 and 4 of the naphthyridone lead template resulted in the identification of several biochemically potent analogues. A lack of corresponding whole cell antibacterial activity is thought to be a consequence of poor cellular penetration as evidenced by the enhancement of activity observed for a lead analogue tested in the presence of a cell permeabilizing agent. (C) 2004 Elsevier Ltd. All rights reserved.