N-glycyl-glycine-2-[(methylphenylmethyl)amino]ethylamide | 320577-28-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-glycyl-glycine-2-[(methylphenylmethyl)amino]ethylamide
• 英文别名: 2-amino-N-[2-[2-[benzyl(methyl)amino]ethylamino]-2-oxoethyl]acetamide
• CAS: 320577-28-4
• 化学式: C₁₄H₂₂N₄O₂
• 分子量: 278.354
• InChiKey: LZZIZLIYYYAEAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  87.5
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-哌啶基乙酸 、 N-glycyl-glycine-2-[(methylphenylmethyl)amino]ethylamide 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 以80%的产率得到N-(1-piperidinomethylcarbonyl)glycyl-glycine-2-[(methylphenylmethyl)amino]ethylamide
  参考文献：
  名称：

  Non-depolarizing Neuromuscular Blocking Activity of Bisquaternary Amino Di- and Tripeptide Derivatives

  摘要：

  Herein we describe the synthesis of novel di- and tripeptide derivatives with two quaternary nitrogen groups attached and the biological testing of these compounds for neuromuscular blocking (NMB) activity in vitro and in vivo. The short peptide scaffold was selected because it offers potential for desired distance between the two pharmacophoric quaternary nitrogen groups, short duration of action, straightforward synthesis, and compatibility with an injectable formulation. From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED90 = 0.68, 0.23, 0.16, 5.04 mu mol/kg, respectively). These new peptide derivatives 20c,e have similar potency and onset time but longer duration and slower recovery than the clinically used reference compounds. The structure-activity relationships described for this chemical series lead to the conclusion that the di- or tripeptide fragment can be regarded as an alternative template to the steroid or aliphatic ester of previously reported NMBs and within this tripeptide-derived series clog P correlates well with in vitro NMB activity.

  DOI：

  10.1021/jm0010062
• 作为产物：
  描述：

  N-甲基-N-苄基-1,2-乙二胺 在 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N-glycyl-glycine-2-[(methylphenylmethyl)amino]ethylamide
  参考文献：
  名称：

  Non-depolarizing Neuromuscular Blocking Activity of Bisquaternary Amino Di- and Tripeptide Derivatives

  摘要：

  Herein we describe the synthesis of novel di- and tripeptide derivatives with two quaternary nitrogen groups attached and the biological testing of these compounds for neuromuscular blocking (NMB) activity in vitro and in vivo. The short peptide scaffold was selected because it offers potential for desired distance between the two pharmacophoric quaternary nitrogen groups, short duration of action, straightforward synthesis, and compatibility with an injectable formulation. From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED90 = 0.68, 0.23, 0.16, 5.04 mu mol/kg, respectively). These new peptide derivatives 20c,e have similar potency and onset time but longer duration and slower recovery than the clinically used reference compounds. The structure-activity relationships described for this chemical series lead to the conclusion that the di- or tripeptide fragment can be regarded as an alternative template to the steroid or aliphatic ester of previously reported NMBs and within this tripeptide-derived series clog P correlates well with in vitro NMB activity.

  DOI：

  10.1021/jm0010062

文献信息

• Non-depolarizing Neuromuscular Blocking Activity of Bisquaternary Amino Di- and Tripeptide Derivatives
  作者：Leo H. D. J. Booij、Leon A. G. M. van der Broek、Wilson Caulfield、Brigitte M. G. Dommerholt-Caris、John K. Clark、Jan van Egmond、Ross McGuire、Alan W. Muir、Harry C. J. Ottenheijm、David C. Rees

  DOI：10.1021/jm0010062

  日期：2000.12.1

  Herein we describe the synthesis of novel di- and tripeptide derivatives with two quaternary nitrogen groups attached and the biological testing of these compounds for neuromuscular blocking (NMB) activity in vitro and in vivo. The short peptide scaffold was selected because it offers potential for desired distance between the two pharmacophoric quaternary nitrogen groups, short duration of action, straightforward synthesis, and compatibility with an injectable formulation. From a small series of compounds 20c,e are identified as effective non-depolarizing NMB agents in vitro and in vivo in anesthetized cats and Rhesus monkeys with potencies similar to those of the clinical reference compounds rocuronium (4) and suxamethonium (2) (monkey ED90 = 0.68, 0.23, 0.16, 5.04 mu mol/kg, respectively). These new peptide derivatives 20c,e have similar potency and onset time but longer duration and slower recovery than the clinically used reference compounds. The structure-activity relationships described for this chemical series lead to the conclusion that the di- or tripeptide fragment can be regarded as an alternative template to the steroid or aliphatic ester of previously reported NMBs and within this tripeptide-derived series clog P correlates well with in vitro NMB activity.