Indole naphthyridinone 32

• 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: Indole naphthyridinone 32
• 英文别名: (E)-N-methyl-3-(7-oxo-6,8-dihydro-5H-1,8-naphthyridin-3-yl)-N-[(1,2,7-trimethylindol-3-yl)methyl]prop-2-enamide
• 化学式: C₂₄H₂₆N₄O₂
• 分子量: 402.496
• InChiKey: RBOIMOUDCYEGGN-DHZHZOJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1,2,7-trimethyl-1H-indole-3-carboxaldehyde 在 sodium tetrahydroborate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 Indole naphthyridinone 32
  参考文献：
  名称：

  Indole Naphthyridinones as Inhibitors of Bacterial Enoyl-ACP Reductases FabI and FabK

  摘要：

  Bacterial enoyl-ACP reductase (FabI) is responsible for catalyzing the final step of bacterial fatty acid biosynthesis and is an attractive target for the development of novel antibacterial agents. Previously we reported the development of FabI inhibitor 4 with narrow spectrum antimicrobial activity and in vivo efficacy against Staphylococcus aureus via intraperitoneal. (ip) administration. Through iterative medicinal chemistry aided by X-ray crystal structure analysis, a new series of inhibitors has been developed with greatly increased potency against FabI-containing organisms. Several of these new inhibitors have potent antibacterial activity against multidrug resistant strains of S. aureus, and compound 30 demonstrates exceptional oral (po) in vivo efficacy in a S. aureus infection model in rats. While optimizing FabI inhibitory activity, compounds 29 and 30 were identified as having low micromolar FabK inhibitory activity, thereby increasing the antimicrobial spectrum of these compounds to include the FabK-containing pathogens Streptococcus pneumoniae and Enterococcus faecalis. The results described herein support the hypothesis that bacterial enoyl-ACP reductases are valid targets for antibacterial agents.

  DOI：

  10.1021/jm0204035

文献信息

• Fab I inhibitors
  申请人：Burgess J. Walter

  公开号：US20060116394A1

  公开（公告）日：2006-06-01

  Compounds are disclosed which are Fab I inhibitors and are useful in the treatment bacterial infections.

  本发明揭示了一种Fab I抑制剂，可用于治疗细菌感染。
• Compositions comprising multiple bioactive agents, and methods of using the same
  申请人：Berman M. Judd

  公开号：US20060142265A1

  公开（公告）日：2006-06-29

  In part, the present invention is directed to compositions comprising a FabI inhibitor and at least one other bioactive agent. In another part, the present invention is directed to antibacterial compositions comprising a compound of formulas I-III and at least one other antibacterial agent.

  本发明的一部分涉及含有FabI抑制剂和至少一种其他生物活性剂的组合物。另一部分，本发明涉及含有I-III式化合物和至少一种其他抗菌剂的抗菌组合物。
• Fab I Inhibitors
  申请人：Burgess Walter J.

  公开号：US20090221699A1

  公开（公告）日：2009-09-03

  Compounds are disclosed which are Fab I inhibitors and are useful in the treatment bacterial infections.

  本发明揭示了一种Fab I抑制剂，可用于治疗细菌感染。
• Compositions Comprising Multiple Bioactive Agents, and Methods of Using the Same
  申请人：BERMAN JUDD M.

  公开号：US20120010127A1

  公开（公告）日：2012-01-12

  In part, the present invention is directed to compositions comprising a FabI inhibitor and at least one other bioactive agent. In another part, the present invention is directed to antibacterial compositions comprising a compound of formulas I-III and at least one other antibacterial agent.

  本发明的一部分涉及包含FabI抑制剂和至少一种其他生物活性剂的组合物。另一部分涉及包含I-III式化合物和至少一种其他抗菌剂的抗菌组合物。
• Compounds for Treatment of Bovine Mastitis
  申请人：Hafkin Barry

  公开号：US20130281442A1

  公开（公告）日：2013-10-24

  Described herein are methods of treating mastitis in female mammals, e.g., cows, wherein the methods may include administering to mammals in need thereof compounds disclosed herein.

  本文描述了治疗雌性哺乳动物（例如奶牛）乳腺炎的方法，其中该方法可能包括向需要该化合物的哺乳动物施用此处披露的化合物。