methyl (2R)-2-acetamide-3-(3-quinolyl)propanoate | 95200-91-2

• 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: methyl (2R)-2-acetamide-3-(3-quinolyl)propanoate
• CAS: 95200-91-2
• 化学式: C₁₅H₁₆N₂O₃
• 分子量: 272.304
• InChiKey: DOEOVRRXJQEFAZ-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.45
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  68.29
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-acetamide-3-(3-quinolyl)propanoate 在 盐酸 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-Fmoc-D-3-(3-quinolyl)alanine
  参考文献：
  名称：

  SSTR1- and SSTR3-Selective Somatostatin Analogues

  摘要：

  AbstractWe prepared the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla, 1) in multigram scale by asymmetric hydrogenation. These amino acids, protected as Fmoc derivatives, were then used in the solid‐phase synthesis of two new somatostatin 14 (SRIF‐14) analogues 8 a and 8 b, tetradecapeptides in which the tryptophan residue (Trp8) is replaced by one of the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla8) and therefore lack the NH bond in residue 8. The selectivity of these new analogues for the somatostatin receptors, SSTR1–5, was measured. Substitution with L‐Qla8 yielded peptide 8 a, which was highly selective for SSTR1 and SSTR3, with an affinity similar to that of SRIF‐14. Substitution by D‐Qla gave the relatively selective analogue 8 b, which showed high affinity for SSTR3 and significant affinity for SSTR1, SSTR2 and SSTR5. The biological results demonstrate that bulky and electronically poor aromatic amino acids at position 8 are compatible with strong activity with SSTR1 and SSTR3. Remarkably, these high affinity levels were achieved with peptides in which the conformational mobility was increased with respect to that of SRIF‐14. This observation suggests that conformational rigidity is not required, and might be detrimental to the interaction with receptors SSTR1 and SSTR3. The absence of an indole N proton in Qla8 might also contribute to the increased flexibility observed in these analogues.

  DOI：

  10.1002/cbic.201000597
• 作为产物：
  描述：

  2-n-(乙酰基氨基)-二甲基膦乙酸甲酯 在 (-)-1,2-bis-((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene) rhodium(I) trifluoromethanesulfonate 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 20.0~25.0 ℃ 、4.0 MPa 条件下， 反应 27.5h， 生成 methyl (2R)-2-acetamide-3-(3-quinolyl)propanoate
  参考文献：
  名称：

  SSTR1- and SSTR3-Selective Somatostatin Analogues

  摘要：

  AbstractWe prepared the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla, 1) in multigram scale by asymmetric hydrogenation. These amino acids, protected as Fmoc derivatives, were then used in the solid‐phase synthesis of two new somatostatin 14 (SRIF‐14) analogues 8 a and 8 b, tetradecapeptides in which the tryptophan residue (Trp8) is replaced by one of the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla8) and therefore lack the NH bond in residue 8. The selectivity of these new analogues for the somatostatin receptors, SSTR1–5, was measured. Substitution with L‐Qla8 yielded peptide 8 a, which was highly selective for SSTR1 and SSTR3, with an affinity similar to that of SRIF‐14. Substitution by D‐Qla gave the relatively selective analogue 8 b, which showed high affinity for SSTR3 and significant affinity for SSTR1, SSTR2 and SSTR5. The biological results demonstrate that bulky and electronically poor aromatic amino acids at position 8 are compatible with strong activity with SSTR1 and SSTR3. Remarkably, these high affinity levels were achieved with peptides in which the conformational mobility was increased with respect to that of SRIF‐14. This observation suggests that conformational rigidity is not required, and might be detrimental to the interaction with receptors SSTR1 and SSTR3. The absence of an indole N proton in Qla8 might also contribute to the increased flexibility observed in these analogues.

  DOI：

  10.1002/cbic.201000597