N-3-carboxypropyl-N-methyl-N′-hydroxyguanidine | 1443827-01-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-3-carboxypropyl-N-methyl-N′-hydroxyguanidine
• 英文别名: 4-[[(E)-N'-hydroxycarbamimidoyl]-methylamino]butanoic acid
• CAS: 1443827-01-7
• 化学式: C₆H₁₃N₃O₃
• 分子量: 175.188
• InChiKey: YAMWPQSBGSMUAE-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：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  99.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-3-carboxypropyl-N-methylcyanamide 在 盐酸羟胺 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 N-3-carboxypropyl-N-methyl-N′-hydroxyguanidine
  参考文献：
  名称：

  Development and Characterization of Glutamyl-Protected N-Hydroxyguanidines as Reno-Active Nitric Oxide Donor Drugs with Therapeutic Potential in Acute Renal Failure

  摘要：

  Acute renal failure (ARF) has high mortality and no effective treatment. Nitric oxide (NO) delivery represents a credible means of preventing the damaging effects of vasoconstriction, central to ARF, but design of drugs with the necessary renoselectivity is challenging. Here, we developed N-hydroxyguanidine NO donor drugs that were protected against spontaneous NO release by linkage to glutamyl adducts that could be cleaved by gamma-glutamyl transpeptidase (gamma-GT), found predominantly in renal tissue. Parent NO donor drug activity was optimized in advance of glutamyl adduct prodrug design. A lead compound that was a suitable substrate for gamma-GT-mediated deprotection was identified. Metabolism of this prodrug to the active parent compound was confirmed in rat kidney homogenates, and the prodrug was shown to be an active vasodilator in rat isolated perfused kidneys (EC50 similar to 50 mu M). The data confirm that glutamate protection of N-hydroxyguanidines is an approach that might hold promise in ARF.

  DOI：

  10.1021/jm400146r

文献信息

• Development and Characterization of Glutamyl-Protected <i>N</i>-Hydroxyguanidines as Reno-Active Nitric Oxide Donor Drugs with Therapeutic Potential in Acute Renal Failure
  作者：Qingzhi Zhang、Philip Milliken、Agnieszka Kulczynska、Alex M. Z. Slawin、Adele Gordon、Nicholas S. Kirkby、David J. Webb、Nigel P. Botting、Ian L. Megson

  DOI：10.1021/jm400146r

  日期：2013.7.11

  Acute renal failure (ARF) has high mortality and no effective treatment. Nitric oxide (NO) delivery represents a credible means of preventing the damaging effects of vasoconstriction, central to ARF, but design of drugs with the necessary renoselectivity is challenging. Here, we developed N-hydroxyguanidine NO donor drugs that were protected against spontaneous NO release by linkage to glutamyl adducts that could be cleaved by gamma-glutamyl transpeptidase (gamma-GT), found predominantly in renal tissue. Parent NO donor drug activity was optimized in advance of glutamyl adduct prodrug design. A lead compound that was a suitable substrate for gamma-GT-mediated deprotection was identified. Metabolism of this prodrug to the active parent compound was confirmed in rat kidney homogenates, and the prodrug was shown to be an active vasodilator in rat isolated perfused kidneys (EC50 similar to 50 mu M). The data confirm that glutamate protection of N-hydroxyguanidines is an approach that might hold promise in ARF.