3-[[5-(2-Ethylphenyl)naphthalene-2-carbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid | 1210057-62-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[[5-(2-Ethylphenyl)naphthalene-2-carbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 1210057-62-7
• 化学式: C₃₀H₂₈N₂O₅
• 分子量: 496.563
• InChiKey: CUBZTNYSYQGMFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-[[5-(2-Ethylphenyl)naphthalene-2-carbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid 在 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 以54%的产率得到rac-2-amino-3-{[5-(2-ethylphenyl)naphthalene-2-carbonyl]amino}propionic 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：

  Methyl 3-[[5-(2-ethylphenyl)naphthalene-2-carbonyl]amino]-2-(phenylmethoxycarbonylamino)propanoate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 以96%的产率得到3-[[5-(2-Ethylphenyl)naphthalene-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

文献信息

• 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 <i>N</i>-Methyl-<scp>d</scp>-aspartate (NMDA) Receptor Complex
  作者：Stephan Urwyler、Philipp Floersheim、Bernard L. Roy、Manuel Koller

  DOI：10.1021/jm900363q

  日期：2009.8.27

  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.