D-(benzyloxycarbonyl)-β-tert-butylaspartylglycinamide | 146349-33-9

• 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: D-(benzyloxycarbonyl)-β-tert-butylaspartylglycinamide
• 英文别名: tert-butyl (3R)-4-[(2-amino-2-oxoethyl)amino]-4-oxo-3-(phenylmethoxycarbonylamino)butanoate
• CAS: 146349-33-9
• 化学式: C₁₈H₂₅N₃O₆
• 分子量: 379.413
• InChiKey: RIZYEUOTWSSRMC-CYBMUJFWSA-N

物化性质

• 沸点：
  666.0±55.0 °C(predicted)
• 密度：
  1.222±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  27
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  137
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  D-(benzyloxycarbonyl)-β-tert-butylaspartylglycinamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 1.17h， 以99%的产率得到D-β-tert-butylaspartylglycinamide
  参考文献：
  名称：

  Synthesis and dopamine receptor modulating activity of lactam conformationally constrained analogs of Pro-Leu-Gly-NH2

  摘要：

  A series of analogues of the potent analogue of Pro-Leu-Gly-NH2 (PLG), 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacetamide (2) were synthesized in which the (R)-gamma-lactam residue of 2 was replaced with a (R)-beta-lactam, (R)-aminosuccinimide, (R)-cycloseryl, (R)-delta-lactam, (R)-epsilon-lactam, or (S)-epsilon-lactam residue to give analogues 3-8, respectively. These substitutions were made so as to vary the psi2 torsion angle. The analogues were tested for their ability to enhance the binding of the dopamine receptor agonist ADTN to the dopamine receptor. Analogues 3-6 and 8 exhibited dose-response curves that were bell-shaped in nature with the maximum effect occurring at a concentration of 1 muM. Analogue 7 was inactive. Analogues 3 and 4 were found to be as effective as PLG, while analogues 5, 6, and 8 appeared to be more effective than PLG in terms of enhancing the binding of ADTN to dopamine receptors. The activity of analogues 3-6 and 8 with their psi2 angles in the vicinity of that observed in a type II beta-turn is consistent with the hypothesis that this type of turn is the bioactive conformation of PLG.

  DOI：

  10.1021/jm00054a010
• 作为产物：
  描述：

  甘氨酰胺盐酸盐 、 Cbz-D-天冬氨酸 4-叔丁酯一水物 在 N-羟基丁二酰亚胺 、 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， 以96.6%的产率得到D-(benzyloxycarbonyl)-β-tert-butylaspartylglycinamide
  参考文献：
  名称：

  Synthesis and dopamine receptor modulating activity of lactam conformationally constrained analogs of Pro-Leu-Gly-NH2

  摘要：

  A series of analogues of the potent analogue of Pro-Leu-Gly-NH2 (PLG), 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacetamide (2) were synthesized in which the (R)-gamma-lactam residue of 2 was replaced with a (R)-beta-lactam, (R)-aminosuccinimide, (R)-cycloseryl, (R)-delta-lactam, (R)-epsilon-lactam, or (S)-epsilon-lactam residue to give analogues 3-8, respectively. These substitutions were made so as to vary the psi2 torsion angle. The analogues were tested for their ability to enhance the binding of the dopamine receptor agonist ADTN to the dopamine receptor. Analogues 3-6 and 8 exhibited dose-response curves that were bell-shaped in nature with the maximum effect occurring at a concentration of 1 muM. Analogue 7 was inactive. Analogues 3 and 4 were found to be as effective as PLG, while analogues 5, 6, and 8 appeared to be more effective than PLG in terms of enhancing the binding of ADTN to dopamine receptors. The activity of analogues 3-6 and 8 with their psi2 angles in the vicinity of that observed in a type II beta-turn is consistent with the hypothesis that this type of turn is the bioactive conformation of PLG.

  DOI：

  10.1021/jm00054a010