Boc-Trp-Lys(Cbz)-(N-Me)Asp(OBn)-(N-Me)Phe-NH2 | 159312-31-9

• 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: Boc-Trp-Lys(Cbz)-(N-Me)Asp(OBn)-(N-Me)Phe-NH2
• 英文别名: Boc-Trp-Lys(Cbz)(Cbz)-N(Me)Asp(OBn)(OBn)-N(Me)Phe-NH2；benzyl (3S)-4-[[(2S)-1-amino-1-oxo-3-phenylpropan-2-yl]-methylamino]-3-[[(2S)-2-[[(2S)-3-(1H-indol-3-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoyl]amino]-6-(phenylmethoxycarbonylamino)hexanoyl]-methylamino]-4-oxobutanoate
• CAS: 159312-31-9
• 化学式: C₅₂H₆₃N₇O₁₀
• 分子量: 946.113
• InChiKey: WTSJOLYMRRMKCZ-ITMZJIMRSA-N

物化性质

• 沸点：
  1133.0±65.0 °C(predicted)
• 密度：
  1.248±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  69
• 可旋转键数：
  27
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  232
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Boc-Trp-Lys(Cbz)-(N-Me)Asp(OBn)-(N-Me)Phe-NH2 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Boc-Trp-Lys(2-thienylacryloyl)-(N-Me)Asp-(N-Me)Phe-NH2
  参考文献：
  名称：

  CCK-A-Selective Tetrapeptides Containing Lys(N.epsilon.)-Amide Residues: Favorable in vivo and in vitro Effects of N-Methylation at the Aspartyl Residue

  摘要：

  Previous structure-activity studies on a series of CCK-A selective tetrapeptide agonists, typified by A-71623 (Boc-Trp-Lys(CONH-Ph-o-Me)-Asp-(N-Me)Phe-NH2), have shown that replacement of the Lys(N-epsilon-carbamoyl) substituent with N-epsilon-acyl substituents resulted in partial agonists with moderate to high affinities for the CCK-A receptor and that replacement of the C-terminal dipeptide with either (N-Me)Asp-Phe or (N-Me)Asp-(N-Me)Phe was highly favorable to in vitro and in vivo CCK activity. The present study demonstrates that although analogues in the epsilon-amide series that are N-methylated at the Phe position are weakly active or inactive in an in vivo rat appetite suppression assay, incorporation of (N-Me)Asp or (N-Me)Asp-(N-Me)Phe modifications in this series results in analogues with markedly improved in vivo activity. In in vitro assays, there is minimal effect of N-methylation pattern on binding affinity, whereas there is a trend toward improved functional activity in the phosphatidylinositol hydrolysis assay in analogues containing (N-Me)Asp.

  DOI：

  10.1021/jm00037a006
• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 、 (S)-3-[((S)-2-Amino-6-benzyloxycarbonylamino-hexanoyl)-methyl-amino]-N-((S)-1-carbamoyl-2-phenyl-ethyl)-N-methyl-succinamic acid benzyl ester; compound with trifluoro-acetic acid 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， 生成 Boc-Trp-Lys(Cbz)-(N-Me)Asp(OBn)-(N-Me)Phe-NH2
  参考文献：
  名称：

  CCK-A-Selective Tetrapeptides Containing Lys(N.epsilon.)-Amide Residues: Favorable in vivo and in vitro Effects of N-Methylation at the Aspartyl Residue

  摘要：

  Previous structure-activity studies on a series of CCK-A selective tetrapeptide agonists, typified by A-71623 (Boc-Trp-Lys(CONH-Ph-o-Me)-Asp-(N-Me)Phe-NH2), have shown that replacement of the Lys(N-epsilon-carbamoyl) substituent with N-epsilon-acyl substituents resulted in partial agonists with moderate to high affinities for the CCK-A receptor and that replacement of the C-terminal dipeptide with either (N-Me)Asp-Phe or (N-Me)Asp-(N-Me)Phe was highly favorable to in vitro and in vivo CCK activity. The present study demonstrates that although analogues in the epsilon-amide series that are N-methylated at the Phe position are weakly active or inactive in an in vivo rat appetite suppression assay, incorporation of (N-Me)Asp or (N-Me)Asp-(N-Me)Phe modifications in this series results in analogues with markedly improved in vivo activity. In in vitro assays, there is minimal effect of N-methylation pattern on binding affinity, whereas there is a trend toward improved functional activity in the phosphatidylinositol hydrolysis assay in analogues containing (N-Me)Asp.

  DOI：

  10.1021/jm00037a006