2-benzyloxycarbonylamino-3-[(4-bromo-1H-indole-2-carbonyl)amino]propionic acid methyl ester | 1182349-15-0

• 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: 2-benzyloxycarbonylamino-3-[(4-bromo-1H-indole-2-carbonyl)amino]propionic acid methyl ester
• 英文别名: methyl 3-[(4-bromo-1H-indole-2-carbonyl)amino]-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 1182349-15-0
• 化学式: C₂₁H₂₀BrN₃O₅
• 分子量: 474.311
• InChiKey: UNEJDJCKVBDWBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyloxycarbonylamino-3-[(4-bromo-1H-indole-2-carbonyl)amino]propionic acid methyl ester 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 以97%的产率得到3-[(4-bromo-1H-indole-2-carbonyl)amino]-2-(phenylmethoxycarbonylamino)propanoic acid
  参考文献：
  名称：

  Drug Design, in Vitro Pharmacology, and Structure−Activity Relationships of 3-Acylamino-2-aminopropionic Acid Derivatives, a Novel Class of Partial Agonists at the Glycine Site on the N-Methyl-d-aspartate (NMDA) Receptor Complex

  摘要：

  Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or D-serine has proven to be difficult because in the vicinity of the alpha-amino acid group little substitution is tolerated. We have solved this problem by replacing the hydroxy group of D-serine with an amido group, thus keeping the hydrogen donor function and allowing For further substitution and exploration of the adjacent space. Heterocyclic substitutions resulted in a series of 3-acylamino-2-aminopropionic acid derivatives, with high affinities in a binding assay for the glycine site. In a functional assay assessing the activation of the glycine site, these compounds displayed a wide range of intrinsic efficacies, from antagonism to a high degree of partial agonism. Structure-activity relationships reveal that lipophilic substituents, presumably filling an additional hydrophobic pocket, are accepted by the glycine site, provided that they are separated from the alpha-amino acid group by a short linker.

  DOI：

  10.1021/jm900363q
• 作为产物：
  描述：

  (S)-methyl 3-amino-2-(((benzyloxy)carbonyl)amino)propanoate hydrochloride 、 4-溴吲哚-2-羧酸 在 吡啶 、 N,N'-羰基二咪唑 作用下， 反应 48.0h， 以79%的产率得到2-benzyloxycarbonylamino-3-[(4-bromo-1H-indole-2-carbonyl)amino]propionic acid methyl ester
  参考文献：
  名称：

  Drug Design, in Vitro Pharmacology, and Structure−Activity Relationships of 3-Acylamino-2-aminopropionic Acid Derivatives, a Novel Class of Partial Agonists at the Glycine Site on the N-Methyl-d-aspartate (NMDA) Receptor Complex

  摘要：

  Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or D-serine has proven to be difficult because in the vicinity of the alpha-amino acid group little substitution is tolerated. We have solved this problem by replacing the hydroxy group of D-serine with an amido group, thus keeping the hydrogen donor function and allowing For further substitution and exploration of the adjacent space. Heterocyclic substitutions resulted in a series of 3-acylamino-2-aminopropionic acid derivatives, with high affinities in a binding assay for the glycine site. In a functional assay assessing the activation of the glycine site, these compounds displayed a wide range of intrinsic efficacies, from antagonism to a high degree of partial agonism. Structure-activity relationships reveal that lipophilic substituents, presumably filling an additional hydrophobic pocket, are accepted by the glycine site, provided that they are separated from the alpha-amino acid group by a short linker.

  DOI：

  10.1021/jm900363q