N-phenethyl-N''-hydroxyguanidine hydrochloride | 1443827-12-0

• 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: N-phenethyl-N''-hydroxyguanidine hydrochloride
• 英文别名: N-(4-phenylethyl)-N′-hydroxyguanidine hydrochloride；1-Hydroxy-2-(2-phenylethyl)guanidine;hydrochloride；1-hydroxy-2-(2-phenylethyl)guanidine;hydrochloride
• CAS: 1443827-12-0
• 化学式: C₉H₁₃N₃O*ClH
• 分子量: 215.683
• InChiKey: SHMJDNVQTURJNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.94
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  70.6
• 氢给体数：
  4
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-4-(5-(allyloxy)-4-(((allyloxy)carbonyl)amino)-5-oxopentanamido)butanoic acid 、 N-phenethyl-N''-hydroxyguanidine hydrochloride 在 碳酸氢钠 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以83%的产率得到
  参考文献：
  名称：

  A new class of NO-donor pro-drugs triggered by γ-glutamyl transpeptidase with potential for reno-selective vasodilatation

  摘要：

  这篇通讯描述了一种新型 N-羟基胍（NHG）原药的合成过程，这种原药在δ-谷氨酰转肽酶（δ-GT）的作用下释放一氧化氮（NO），具有治疗急性肾损伤/衰竭（ARI/ARF）的潜力。

  DOI：

  10.1039/c2cc38382a
• 作为产物：
  描述：

  N-phenethylcyanamide 在 盐酸羟胺 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 N-phenethyl-N''-hydroxyguanidine hydrochloride
  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.
• A new class of NO-donor pro-drugs triggered by γ-glutamyl transpeptidase with potential for reno-selective vasodilatation
  作者：Qingzhi Zhang、Agnieszka Kulczynska、David J. Webb、Ian L. Megson、Nigel P. Botting

  DOI：10.1039/c2cc38382a

  日期：——

  This communication describes the synthesis of a new class of N-hydroxyguanidine (NHG) pro-drugs which release nitric oxide (NO), triggered by the action of γ-glutamyl transpeptidase (γ-GT), and have potential for the treatment of acute renal injury/failure (ARI/ARF).

  这篇通讯描述了一种新型 N-羟基胍（NHG）原药的合成过程，这种原药在δ-谷氨酰转肽酶（δ-GT）的作用下释放一氧化氮（NO），具有治疗急性肾损伤/衰竭（ARI/ARF）的潜力。