benzyl (E)-3-[8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl]acrylate | 335030-40-5

• 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: benzyl (E)-3-[8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl]acrylate
• 英文别名: Benzyl (E)-3-[8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro1,8-naphthyridin-3-yl]acrylate；tert-butyl 6-[(E)-3-oxo-3-phenylmethoxyprop-1-enyl]-3,4-dihydro-2H-1,8-naphthyridine-1-carboxylate
• CAS: 335030-40-5
• 化学式: C₂₃H₂₆N₂O₄
• 分子量: 394.47
• InChiKey: NCWOEWXZSUCGQT-VAWYXSNFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  benzyl (E)-3-[8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl]acrylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 生成 benzyl (E)-3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)prop-2-enoate
  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
• 作为产物：
  描述：

  1,2,3,4-四氢-1,8-萘啶 在 palladium diacetate 、 N-溴代丁二酰亚胺(NBS) 、 P(tolyl)3 、 溶剂黄146 、 N,N-二异丙基乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 90.5h， 生成 benzyl (E)-3-[8-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl]acrylate
  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：Miller H. William

  公开号：US20050250810A1

  公开（公告）日：2005-11-10

  Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.

  公式（I）的化合物被揭示为Fab I抑制剂，可用于治疗细菌感染。
• Fab I inhibitors
  申请人：Miller William H.

  公开号：US06846819B1

  公开（公告）日：2005-01-25

  Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.

  公式（I）的化合物被揭示是Fab I抑制剂，可用于治疗细菌感染。
• Fab I Inhibitors
  申请人：Miller William H.

  公开号：US20080125423A1

  公开（公告）日：2008-05-29

  Compounds of the formula (I) are disclosed which are Fab I inhibitors and are useful in the treatment of bacterial infections.

  公式（I）的化合物被揭示为Fab I抑制剂，可用于治疗细菌感染。
• FAB I INHIBITORS
  申请人：Affinium Pharmaceuticals, Inc.

  公开号：EP1226138B1

  公开（公告）日：2004-12-29
• US7524843B2
  申请人：——

  公开号：US7524843B2

  公开（公告）日：2009-04-28