3',4',3,'',4'''-tetradehydro-3,2',6',2''',6'''-penta-Cbz-neomycin | 1215860-58-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3',4',3,'',4'''-tetradehydro-3,2',6',2''',6'''-penta-Cbz-neomycin
• 英文别名: benzyl N-[[(2R,3R,6S)-2-[(1R,2R,3S,4R,6S)-4-amino-3-hydroxy-2-[(2S,3R,4S,5R)-3-hydroxy-5-(hydroxymethyl)-4-[[(2R,3R,6R)-3-(phenylmethoxycarbonylamino)-6-(phenylmethoxycarbonylaminomethyl)-3,6-dihydro-2H-pyran-2-yl]oxy]oxolan-2-yl]oxy-6-(phenylmethoxycarbonylamino)cyclohexyl]oxy-3-(phenylmethoxycarbonylamino)-3,6-dihydro-2H-pyran-6-yl]methyl]carbamate
• CAS: 1215860-58-4
• 化学式: C₆₃H₇₂N₆O₁₉
• 分子量: 1217.29
• InChiKey: MLCUZNVWYWBPII-AEMCMLKLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  88
• 可旋转键数：
  29
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  334
• 氢给体数：
  9
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  3',4',3,'',4'''-tetradehydro-3,2',6',2''',6'''-penta-Cbz-neomycin 、 (2R)-4-amino-3,3-difluoro-2-hydroxybutanoic acid 在 N-羟基丁二酰亚胺 、 碳酸氢钠 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 24.0h， 生成
  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
• 作为产物：
  描述：

  3',4',3,'',4'''-tetradehydro-1,3,2',6',2''',6'''-hexa-Cbz-neomycin 在 水 、 lithium hydroxide 、 柠檬酸 作用下， 以 N-甲基吡咯烷酮 为溶剂， 生成 3',4',3,'',4'''-tetradehydro-3,2',6',2''',6'''-penta-Cbz-neomycin
  参考文献：
  名称：

  [EN] ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS
  [FR] ANALOGUES D'AMINOGLYCOSIDE ANTIBACTÉRIENS

  摘要：

  公开号：

  WO2011044538A9

文献信息

• [EN] ANTIBACTERIAL AMINOGLYCOSIDE ANALOGS<br/>[FR] ANALOGUES D'AMINOGLYCOSIDES ANTIBACTÉRIENS
  申请人：ACHAOGEN INC

  公开号：WO2010030704A2

  公开（公告）日：2010-03-18

  Compounds having antibacterial activity are disclosed. The compounds have the following structure (I) including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein Q1, Q2, Z1, Z2, Z3, Z4, R1, R2 and R3 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.