(2S,3S)-4-azido-2,3-bis-benzyloxybutanoic acid | 1215861-38-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,3S)-4-azido-2,3-bis-benzyloxybutanoic acid
• 英文别名: (2S,3S)-4-azido-2,3-bis(phenylmethoxy)butanoic acid
• CAS: 1215861-38-3
• 化学式: C₁₈H₁₉N₃O₄
• 分子量: 341.367
• InChiKey: CVZBHVSLJNLJDU-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (S)-2-((R)-1-benzyloxy-allyl)-oxirane 在 甲醇 、 sodium dihydrogenphosphate 、 sodium azide 、 sodium chloride dihydrate 、 2-甲基-2-丁烯 、 二甲基硫 、 四丁基碘化铵 、 sodium hydride 、 氯化铵 、 臭氧 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 叔丁醇 为溶剂， 生成 (2S,3S)-4-azido-2,3-bis-benzyloxybutanoic acid
  参考文献：
  名称：

  Toxicity Modulation, Resistance Enzyme Evasion, and A-Site X-ray Structure of Broad-Spectrum Antibacterial Neomycin Analogs

  摘要：

  Aminoglycoside antibiotics are pseudosaccharides decorated with ammonium groups that are critical for their potent broad-spectrum antibacterial activity. Despite over three decades of speculation whether or not modulation of pK(a) is a viable strategy to curtail aminoglycoside kidney toxicity, there is a lack of methods to systematically probe amine-RNA interactions and resultant cytotoxicity trends. This study reports the first series of potent aminoglycoside antibiotics harboring fluorinated N1-hydroxyaminobutyryl acyl (HABA) appendages for which fluorine-RNA contacts are revealed through an X-ray cocrystal structure within the RNA A-site. Cytotoxicity in kidney-derived cells was significantly reduced for the derivative featuring our novel beta,beta-difluoro-HABA group, which masks one net charge by lowering the pK(a) without compromising antibacterial potency. This novel side-chain assists in evasion of aminoglycoside-modifying enzymes, and it can be easily transferred to impart these properties onto any number of novel analogs.

  DOI：

  10.1021/cb5003416

文献信息

• ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
  申请人：Aggen James Bradley

  公开号：US20110275586A1

  公开（公告）日：2011-11-10

  Compounds having antibacterial activity are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q 1 , Q 2 , Z 1 , Z 2 , Z 3 , Z 4 , R 1 , R 2 and R 3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

  本文披露了具有抗菌活性的化合物。该化合物具有以下结构（I）：包括立体异构体、药学上可接受的盐和前药，其中Q1、Q2、Z1、Z2、Z3、Z4、R1、R2和R3的定义如本文所述。本文还披露了与制备和使用此类化合物相关的方法，以及包含此类化合物的制药组合物。
• AMINOGLYCOSIDE DOSING REGIMENS
  申请人：Bruss Jon B.

  公开号：US20120208781A1

  公开（公告）日：2012-08-16

  The present invention provides new aminoglycoside dosing regimens associated with enhanced microbicidal activity and reduced nephrotoxicity, as well as methods of using these dosing regimens to treat various bacterial infections.

  本发明提供了新的氨基糖苷类药物给药方案，与增强微生物杀灭活性和降低肾毒性有关，并提供了使用这些给药方案治疗各种细菌感染的方法。
• [EN] ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS<br/>[FR] ANALOGUES ANTIBACTÉRIENS D'AMINOGLYCOSIDES
  申请人：ACHAOGEN INC

  公开号：WO2011044498A9

  公开（公告）日：2012-02-09
• [EN] ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS<br/>[FR] ANALOGUES D'AMINOGLYCOSIDE ANTIBACTÉRIENS
  申请人：ACHAOGEN INC

  公开号：WO2011044503A9

  公开（公告）日：2012-02-09
• US8367625B2
  申请人：——

  公开号：US8367625B2

  公开（公告）日：2013-02-05