Boc-D-Trp-β-homo-D-Leu-Asp-Phe-NH2 | 118333-40-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: Boc-D-Trp-β-homo-D-Leu-Asp-Phe-NH2
• 英文别名: Boc-D-Trp-bAla(3R-iBu)-Asp-Phe-NH2；(3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(3R)-3-[[(2R)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-5-methylhexanoyl]amino]-4-oxobutanoic acid
• CAS: 118333-40-7
• 化学式: C₃₆H₄₈N₆O₈
• 分子量: 692.813
• InChiKey: YXOOYMGXDFIVOI-KULMNKMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  50
• 可旋转键数：
  19
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  222
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  Z-D-Leu-CHN2 在 palladium on activated charcoal N-甲基吗啉 、 sodium hydroxide 、 氢气 、 silver benzoate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 25.0~30.0 ℃ 、101.33 kPa 条件下， 反应 37.5h， 生成 Boc-D-Trp-β-homo-D-Leu-Asp-Phe-NH2
  参考文献：
  名称：

  Synthesis of gastrin antagonists, analogs of the C-terminal tetrapeptide of gastrin, by introduction of a .beta.-homo residue

  摘要：

  A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.

  DOI：

  10.1021/jm00123a003

文献信息

• Synthesis of gastrin antagonists, analogs of the C-terminal tetrapeptide of gastrin, by introduction of a .beta.-homo residue
  作者：M. Rodriguez、P. Fulcrand、J. Laur、A. Aumelas、J. P. Bali、Jean Martinez

  DOI：10.1021/jm00123a003

  日期：1989.3

  A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.