[(S)-1-[(R)-1-({[Ethyl-(2-thiophen-2-yl-ethyl)-carbamoyl]-methyl}-carbamoyl)-4-guanidino-butylcarbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester | 119745-58-3

• 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: [(S)-1-[(R)-1-({[Ethyl-(2-thiophen-2-yl-ethyl)-carbamoyl]-methyl}-carbamoyl)-4-guanidino-butylcarbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester
• CAS: 119745-58-3
• 化学式: C₃₀H₄₅N₇O₆S
• 分子量: 631.797
• InChiKey: HZBCIVZSDSDBJX-RPWUZVMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.84
• 重原子数：
  44.0
• 可旋转键数：
  16.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  198.97
• 氢给体数：
  7.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [(S)-1-[(R)-1-({[Ethyl-(2-thiophen-2-yl-ethyl)-carbamoyl]-methyl}-carbamoyl)-4-guanidino-butylcarbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester 在 盐酸 、 苯甲醚 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 acetic acid;(2R)-5-(diaminomethylideneamino)-2-[[(2S)-2-(diaminomethylideneamino)-3-(4-hydroxyphenyl)propanoyl]amino]-N-[2-[ethyl(2-thiophen-2-ylethyl)amino]-2-oxoethyl]pentanamide
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides

  摘要：

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

  DOI：

  10.1021/jm00125a028
• 作为产物：
  描述：

  N-Ethyl-2-(2-thienyl)ethylamine hydrochloride 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 溶剂黄146 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 97.0h， 生成 [(S)-1-[(R)-1-({[Ethyl-(2-thiophen-2-yl-ethyl)-carbamoyl]-methyl}-carbamoyl)-4-guanidino-butylcarbamoyl]-2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Peripherally acting enkephalin analogs. 2. Polar tri- and tetrapeptides

  摘要：

  The design, synthesis, and biological activity of a series of D-Arg2-enkephalin-derived tetrapeptide amides and tripeptide aralkylamides are reported. These polar analogues were designed to be excluded from the central nervous system with their action thus limited to peripheral opioid receptors. The effects of the nature of the aromatic ring, aryl ring substitution, and aralkylamine chain length on activity were investigated; in a number of cases the N-terminal amino group of Tyr1 was converted to a guanidino group to further increase hydrophilicity. The peptides were all synthesized by classical solution methodology. The opioid activity of the peptides was assessed in vitro on the guinea pig ileum and their antinociceptive activity was determined in vivo in chemically induced writhing models (peripheral activity) and in the hot-plate test (central activity), in rodents. That the analgesic effects were predominantly mediated in the periphery was demonstrated by antagonism of antinociception by the peripheral opioid antagonist N-methylnalorphine and by comparison of the activities in the writhing and hot-plate tests. As a class, the tetrapeptides were more potent than the tripeptides; N alpha-amidination generally increased activity. A number of compounds exhibited very potent opioid activity and had the desired pharmacological profile, indicating a high degree of peripheral selectivity.

  DOI：

  10.1021/jm00125a028