(2S,5R)-5-(((2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)methyl)-amino)-N-(6-methoxy-1,5-naphthyridin-4-yl)tetrahydro-2H-pyran-2-carboxamide | 881654-46-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,5R)-5-(((2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)methyl)-amino)-N-(6-methoxy-1,5-naphthyridin-4-yl)tetrahydro-2H-pyran-2-carboxamide
• 英文别名: (2S,5R)-5-(2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethylamino)-N-(6-methoxy-1,5-naphthyridin-4-yl)oxane-2-carboxamide
• CAS: 881654-46-2
• 化学式: C₂₃H₂₅N₅O₅
• 分子量: 451.482
• InChiKey: HDUOQGPJPLEPTI-KDOFPFPSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (2S,5R)-5-[(叔-丁氧羰基)氨基]四氢-2H-吡喃-2-羧酸 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 N-羟基丁二酰亚胺 、 氨 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 乙酸乙酯 、 1,2-二氯乙烷 为溶剂， 反应 3.0h， 生成 (2S,5R)-5-(((2,3-dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl)methyl)-amino)-N-(6-methoxy-1,5-naphthyridin-4-yl)tetrahydro-2H-pyran-2-carboxamide
  参考文献：
  名称：

  Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity

  摘要：

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.

  DOI：

  10.1021/jm400963y

文献信息

• Aminopiperidine Quinolines and Their Azaisosteric Analogues with Antibacterial Activity
  申请人：Reck Folkert

  公开号：US20090131444A1

  公开（公告）日：2009-05-21

  The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm blooded animals such as humans.

  本发明涉及表现出抗菌活性的化合物、其制备过程、包含它们作为活性成分的药物组合物、它们作为药物的使用以及它们在制造用于治疗温血动物（如人类）的细菌感染的药物方面的使用。特别地，本发明涉及用于治疗温血动物（如人类）细菌感染的有用化合物，更具体地涉及使用这些化合物制造用于治疗温血动物（如人类）细菌感染的药物。
• AMINOPIPERIDINE QUINOLINES AND THEIR AZAISOSTERIC ANALOGUES WITH ANTIBACTERIAL ACTIVITY
  申请人：AstraZeneca AB

  公开号：EP1891078A1

  公开（公告）日：2008-02-27
• [EN] AMINOPIPERIDINE QUINOLINES AND THEIR AZAISOSTERIC ANALOGUES WITH ANTIBACTERIAL ACTIVITY<br/>[FR] QUINOLEINES D'AMINOPIPERIDINE ET LEURS ANALOGUES AZAISOSTERIQUES PRESENTANT UNE ACTIVITE ANTIBACTERIENNE
  申请人：ASTRAZENECA AB

  公开号：WO2006125974A1

  公开（公告）日：2006-11-30

  [EN] The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm blooded animals such as humans.
  [FR] La présente invention concerne des composés qui présentent une activité antibactérienne, des procédés pour leurs préparations, des compositions pharmaceutiques contenant lesdits composés en tant que principe actif, leur utilisation en tant que médicaments et leur utilisation dans la fabrication de médicaments utilisés dans le traitement d'infections bactériennes chez les homéothermes, tels que les êtres humains. Cette invention concerne en particulier des composés utiles dans le traitement d'infections bactériennes chez les homéothermes, tels que les êtres humains, et plus particulièrement l'utilisation desdits composés dans la fabrication de médicaments utilisés dans le traitement d'infections bactériennes chez les homéothermes, tels que les êtres humains.
• Design, Synthesis, and Characterization of Novel Tetrahydropyran-Based Bacterial Topoisomerase Inhibitors with Potent Anti-Gram-Positive Activity
  作者：Jean-Philippe Surivet、Cornelia Zumbrunn、Georg Rueedi、Christian Hubschwerlen、Daniel Bur、Thierry Bruyère、Hans Locher、Daniel Ritz、Wolfgang Keck、Peter Seiler、Christopher Kohl、Jean-Christophe Gauvin、Azely Mirre、Verena Kaegi、Marina Dos Santos、Mika Gaertner、Jonathan Delers、Michel Enderlin-Paput、Maria Boehme

  DOI：10.1021/jm400963y

  日期：2013.9.26

  There is an urgent need for new antibacterial drugs that are effective against infections caused by multidrug-resistant pathogens. Novel nonfluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) have the potential to become such drugs because they display potent antibacterial activity and exhibit no target-mediated cross-resistance with fluoroquinolones. Bacterial topoisomerase inhibitors that are built on a tetrahydropyran ring linked to a bicyclic aromatic moiety through a syn-diol linker show potent anti-Gram-positive activity, covering isolates with clinically relevant resistance phenotypes. For instance, analog 49c was found to be a dual DNA gyrase topoisomerase IV inhibitor, with broad antibacterial activity and low propensity for spontaneous resistance development, but suffered from high hERG K channel block. On the other hand, analog 49e displayed lower hERG K channel block while retaining potent in vitro antibacterial activity and acceptable frequency for resistance development. Furthermore, analog 49e showed moderate clearance in rat and promising in vivo efficacy against Staphylococcus aureus in a murine infection model.