3,5-dimethylbenzyl 2-<(methoxycarbonyl)amino>-3-(3-indolyl)propionate

• 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: 3,5-dimethylbenzyl 2-<(methoxycarbonyl)amino>-3-(3-indolyl)propionate
• 英文别名: (S)-3-(1H-Indol-3-yl)-2-methoxycarbonylamino-propionic acid 3,5-dimethyl-benzyl ester；(3,5-dimethylphenyl)methyl (2S)-3-(1H-indol-3-yl)-2-(methoxycarbonylamino)propanoate
• 化学式: C₂₂H₂₄N₂O₄
• 分子量: 380.444
• InChiKey: HIAXBDRRMRHHSX-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  80.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 在 盐酸 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 3,5-dimethylbenzyl 2-<(methoxycarbonyl)amino>-3-(3-indolyl)propionate
  参考文献：
  名称：

  Identification of L-Tryptophan Derivatives with Potent and Selective Antagonist Activity at the NK1 Receptor

  摘要：

  As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines. Optimization of substitution on the benzyl ester led to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 26 as a potent and selective substance P receptor antagonist. Compound 26 blocked substance P induced dermal extravasation in vivo and was the most potent compound from this structurally novel class of antagonists which further adds to the diversity of small molecules that bind to the (NK1) receptor.

  DOI：

  10.1021/jm00035a006

文献信息

• Identification of L-Tryptophan Derivatives with Potent and Selective Antagonist Activity at the NK1 Receptor
  作者：Angus M. MacLeod、Kevin J. Merchant、Frederick Brookfield、Fintan Kelleher、Graeme Stevenson、Andrew P. Owens、Christopher J. Swain、Margaret A. Cascieri、Sharon Sadowski

  DOI：10.1021/jm00035a006

  日期：1994.4

  As part of a program of screening the Merck sample collection, N-ethyl-L-tryptophan benzyl ester was identified as a weak antagonist at the substance P (NK1) receptor. Structure-activity studies showed that the indole ring system could be replaced by 3,4-dichlorophenyl, alpha- or beta-naphthyl, or benzthiophene with retention or only small loss of affinity. It was found that acylation of the tryptophan nitrogen gave compounds with higher affinity than N-ethyl or other basic amines. Optimization of substitution on the benzyl ester led to the identification of the 3,5-bis-(trifluoromethyl)benzyl ester of N-acetyl-L-tryptophan 26 as a potent and selective substance P receptor antagonist. Compound 26 blocked substance P induced dermal extravasation in vivo and was the most potent compound from this structurally novel class of antagonists which further adds to the diversity of small molecules that bind to the (NK1) receptor.