3-{2-[2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[(6-hydroxy-naphthalene-2-carbonyl)-amino]-hexanoylamino}-N-(1-carbamoyl-2-phenyl-ethyl)-succinamic acid; hydrate | 131449-22-4

• 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-{2-[2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[(6-hydroxy-naphthalene-2-carbonyl)-amino]-hexanoylamino}-N-(1-carbamoyl-2-phenyl-ethyl)-succinamic acid; hydrate
• 英文别名: (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-6-[(6-hydroxynaphthalene-2-carbonyl)amino]-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]hexanoyl]amino]-4-oxobutanoic acid
• CAS: 131449-22-4
• 化学式: C₄₆H₅₃N₇O₁₀
• 分子量: 863.968
• InChiKey: LZGZBJUVAOQPOU-ZQWQDMLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  63
• 可旋转键数：
  22
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  271
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-{2-[2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[(6-hydroxy-naphthalene-2-carbonyl)-amino]-hexanoylamino}-N-(1-carbamoyl-2-phenyl-ethyl)-succinamic acid; hydrate 在 吡啶 、 pyridinium acetyl sulfate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-6-[(6-sulfooxynaphthalene-2-carbonyl)amino]hexanoyl]amino]-4-oxobutanoic acid
  参考文献：
  名称：

  Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N.epsilon.)-amide residues

  摘要：

  A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(N(epsilon)-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-AT receptor agonists. These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series. A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group of the lysine did not affect affinity for the CCK-AT receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor. The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked by selective CCK-A receptor antagonists.

  DOI：

  10.1021/jm00089a010
• 作为产物：
  描述：

  2-羟基-6-萘甲酸 在 N-甲基吗啉 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 3-{2-[2-tert-Butoxycarbonylamino-3-(1H-indol-3-yl)-propionylamino]-6-[(6-hydroxy-naphthalene-2-carbonyl)-amino]-hexanoylamino}-N-(1-carbamoyl-2-phenyl-ethyl)-succinamic acid; hydrate
  参考文献：
  名称：

  Development of potent and selective CCK-A receptor agonists from Boc-CCK-4: tetrapeptides containing Lys(N.epsilon.)-amide residues

  摘要：

  A series of Boc-CCK-4 derivatives represented by the general structure Boc-Trp-Lys(N(epsilon)-COR)-Asp-Phe-NH2, where R is an aromatic, heterocyclic, or aliphatic group, are potent and selective CCK-AT receptor agonists. These amide-bearing compounds complement the previously described urea-based tetrapeptides (Shiosaki et al. J. Med. Chem. 1991, 34, 2837-2842); structure-activity studies revealed parallel as well as divergent trends between these two series. A significant correlation was observed between pancreatic binding affinity and the resonance constant R of the phenyl substituent in one particular series of derivatives. Sulfation of phenolic amides appended onto the epsilon-amino group of the lysine did not affect affinity for the CCK-AT receptor in contrast to the 500-fold increase in binding potency observed upon sulfation of CCK-8, suggesting that the lysine appendage and the sulfated tyrosine in CCK-8, both key structural elements that impart high affinity for the CCK-A receptor, are interacting differently with the receptor. The amide-bearing tetrapeptides are full agonists relative to CCK-8 in stimulating pancreatic amylase release while being partial agonists in eliciting phosphoinositide (PI) hydrolysis. Both effects were blocked by selective CCK-A receptor antagonists.

  DOI：

  10.1021/jm00089a010