O2-(β-D-N-acetylglucosaminyl) 1-(pyrrolidin-1yl)diazen-1-ium-1,2-diolate | 1037206-68-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: O2-(β-D-N-acetylglucosaminyl) 1-(pyrrolidin-1yl)diazen-1-ium-1,2-diolate
• 英文别名: CV-166
• CAS: 1037206-68-0
• 化学式: C₁₂H₂₂N₄O₇
• 分子量: 334.329
• InChiKey: DZGSQKNEZQWQBT-OOCWMUITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.16
• 重原子数：
  23.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  149.92
• 氢给体数：
  4.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  CV-154 在 甲醇 、 sodium methylate 作用下， 以91%的产率得到O2-(β-D-N-acetylglucosaminyl) 1-(pyrrolidin-1yl)diazen-1-ium-1,2-diolate
  参考文献：
  名称：

  Hydrolytic Reactivity Trends among Potential Prodrugs of the O²-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity

  摘要：

  Glycosylated diazeniumdiolates of structure R(2)NN(O)=NO-R' (R' = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R(2)NN(O)=NO(-) ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R(2)NN(O)=NO-GlcNAc (where R(2)N = diethylamino or pyrrolidin-1-yl and GlcNAc = N-acetylglucosamin-1-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.

  DOI：

  10.1021/jm8000482

文献信息

• Hydrolytic Reactivity Trends among Potential Prodrugs of the O²-Glycosylated Diazeniumdiolate Family. Targeting Nitric Oxide to Macrophages for Antileishmanial Activity
  作者：Carlos A. Valdez、Joseph E. Saavedra、Brett M. Showalter、Keith M. Davies、Thomas C. Wilde、Michael L. Citro、Joseph J. Barchi、Jeffrey R. Deschamps、Damon Parrish、Stefan El-Gayar、Ulrike Schleicher、Christian Bogdan、Larry K. Keefer

  DOI：10.1021/jm8000482

  日期：2008.7

  Glycosylated diazeniumdiolates of structure R(2)NN(O)=NO-R' (R' = a saccharide residue) are potential prodrugs of the nitric oxide (NO)-releasing but acid-sensitive R(2)NN(O)=NO(-) ion. Moreover, cleaving the acid-stable glycosides under alkaline conditions provides a convenient protecting group strategy for diazeniumdiolate ions. Here, we report comparative hydrolysis rate data for five representative glycosylated diazeniumdiolates at pH 14, 7.4, and 3.8-4.6 as background for further developing both the protecting group application and the ability to target NO pharmacologically to macrophages harboring intracellular pathogens. Confirming the potential in the latter application, adding R(2)NN(O)=NO-GlcNAc (where R(2)N = diethylamino or pyrrolidin-1-yl and GlcNAc = N-acetylglucosamin-1-yl) to cultures of infected mouse macrophages that were deficient in inducible NO synthase caused rapid death of the intracellular protozoan parasite Leishmania major with no host cell toxicity.