3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde | 443956-19-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde
• 英文别名: 3,4-Dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-carboxaldehyd；3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carbaldehyde
• CAS: 443956-19-2
• 化学式: C₈H₈N₂O₂
• 分子量: 164.164
• InChiKey: FBWQRJIEBLGXQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  、 3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine-6-carboxaldehyde 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (3R)-3-[[4-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethylamino)-2-oxabicyclo[2.2.2]octan-1-yl]methyl]-5-fluoro-3-hydroxy-1,7-diazatricyclo[6.3.1.04,12]dodeca-4(12),5,7,9-tetraen-11-one
  参考文献：
  名称：

  Hydroxy tricyclic 1,5-naphthyridinone oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents-SAR of RHS moiety (Part-3)

  摘要：

  Novel bacterial topoisomerase inhibitors (NBTIs) are a new class of broad-spectrum antibacterial agents targeting bacterial Gyrase A and ParC and have potential utility in combating antibiotic resistance. (R)-Hydroxy-1,5-naphthyridinone left-hand side (LHS) oxabicyclooctane linked pyridoxazinone right-hand side (RHS) containing NBTIs showed a potent Gram-positive antibacterial profile. SAR around the RHS moiety, including substitutions around pyridooxazinone, pyridodioxane, and phenyl propenoids has been described. A fluoro substituted pyridoxazinone showed an MIC against Staphylococcus aureus of 0.5 mu g/mL with reduced functional hERG activity (IC50 333 mu M) and good in vivo efficacy [ED90 12 mg/kg, intravenous (iv) and 15 mg/kg, oral (p.o.)]. A pyridodioxane-containing NBTI showed a S. aureus MIC of 0.5 mu g/mL, significantly improved hERG IC50 764 mu M and strong efficacy of 11 mg/kg (iv) and 5 mg/kg (p.o.). A phenyl propenoid series of compounds showed potent antibacterial activity, but also showed potent hERG binding activity. Many of the compounds in the hydroxy-tricyclic series showed strong activity against Acinetobacter baumannii, but reduced activity against Escherichia coli and Pseudomonas aeruginosa. Bicyclic heterocycles appeared to be the best RHS moiety for the hydroxy-tricyclic oxabicyclooctane linked NBTIs. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.063

文献信息

• [EN] BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS<br/>[FR] COMPOSÉS BICYCLIQUES PONTÉS POUR LE TRAITEMENT DES INFECTIONS BACTÉRIENNES
  申请人：KYORIN SEIYAKU KK

  公开号：WO2013003383A1

  公开（公告）日：2013-01-03

  Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型桥环双环化合物，以及它们的药用盐、水合物和前药。还披露了包含这些化合物的组合物，制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。所披露的化合物、其药用盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和症状。
• Quinolines and nitrogenated derivative therof substituted in 4-position by a piperidine-containing moiety and their use as antibacterial agents
  申请人：——

  公开号：US20040138219A1

  公开（公告）日：2004-07-15

  Piperidine derivatives of formula (I) and pharmaceutically derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man. 1

  式(I)的哌啶衍生物及其药学衍生物在哺乳动物中，特别是在人类中，用于治疗细菌感染的方法中具有有用价值。
• BRIDGED BICYCLIC COMPOUNDS FOR THE TREATMENT OF BACTERIAL INFECTIONS
  申请人：Fukuda Yasumichi

  公开号：US20140243302A1

  公开（公告）日：2014-08-28

  Novel bridged bicyclic compounds are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antibacterial agents. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating bacterial infections and associated diseases and conditions.

  本文披露了新型桥环双环化合物及其药学上可接受的盐、水合物和前药。还披露了包含这些化合物的组合物、制备这些化合物的方法以及将这些化合物用作抗菌剂的方法。披露的化合物、它们的药学上可接受的盐、水合物和前药，以及包含这些化合物、盐、水合物和前药的组合物，可用于治疗细菌感染及相关疾病和病情。
• QUINOLINES AND NITROGENATED DERIVATIVES THEREOF SUBSTITUTED IN 4-POSITION BY A PIPERIDINE-CONTAINING MOIETY AND THEIR USE AS ANTIBACTERIAL AGENTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP1359908B1

  公开（公告）日：2007-08-22
• US7205408B2
  申请人：——

  公开号：US7205408B2

  公开（公告）日：2007-04-17