N-methyl-N-[N-methyl-N-(1-piperidinomethylcarbonyl)glycyl]glycine | 320577-35-3

• 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-methyl-N-[N-methyl-N-(1-piperidinomethylcarbonyl)glycyl]glycine
• 英文别名: 2-[Methyl-[2-[methyl-(2-piperidin-1-ylacetyl)amino]acetyl]amino]acetic acid
• CAS: 320577-35-3
• 化学式: C₁₃H₂₃N₃O₄
• 分子量: 285.343
• InChiKey: SCJVCUZWIUBHPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-苄基-N,N’-二甲基乙二胺 、 N-methyl-N-[N-methyl-N-(1-piperidinomethylcarbonyl)glycyl]glycine 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以71%的产率得到N-methyl-N-[N-methyl-N-(1-piperidinomethylcarbonyl)glycyl]glycine-N-methyl-2-[(methyl-1-phenylmethyl)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：

  1-哌啶基乙酸 在 sodium hydroxide 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 124.0h， 生成 N-methyl-N-[N-methyl-N-(1-piperidinomethylcarbonyl)glycyl]glycine
  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