methyl (2R)-2-[[(3S)-3-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoyl]amino]-3-phenylpropanoate | 649761-74-0

• 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-[[(3S)-3-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoyl]amino]-3-phenylpropanoate
• CAS: 649761-74-0
• 化学式: C₃₄H₃₉N₃O₇
• 分子量: 601.7
• InChiKey: HNOQXIHXDUUCOW-YTCPBCGMSA-N

物化性质

• 熔点：
  159-161 °C(Solv: ethyl acetate (141-78-6))
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  44
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2R)-2-[[(3S)-3-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoyl]amino]-3-phenylpropanoate 在 N-甲基吗啉 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 methyl (2S)-2-[[(3S)-3-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoyl]amino]-3-phenylpropanoate
  参考文献：
  名称：

  Design, Synthesis, Molecular Modeling Studies, and Calpain Inhibitory Activity of Novel α-Ketoamides Incorporating Polar Residues at the P₁‘-Position

  摘要：

  A series of novel alpha-ketoamides incorporating stereoisomeric residues with different electronic properties at the P-1'-position were synthesized to study the electronic requirements for inhibitor binding to the S-1'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. For example, ester la (CbZ-L-Leu-L-Phe-CO-D-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative 2a (Cbz-L-Leu-L-Phe-CO-D-Phe-OH). Additionally, amidino derivative 3a (CbZ-L-Leu-L-Phe-CONH-D-CH[C(NH)NH2]Bn) was about 6000-fold more potent than 2a. Furthermore, 4a (Cbz-L-Leu-L-Phe-CONHCH2Bn) was 12-fold less potent than its aza analogue 4b (CbZ-L-Leu-L-Phe-CONHNHBn). The results are consistent with the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. The acidic amino acid residue was found to be Glu261 via molecular modeling studies.

  DOI：

  10.1021/jm0301336
• 作为产物：
  描述：

  N-苄氧羰基-L-亮氨酸 在 N-甲基吗啉 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 methyl (2R)-2-[[(3S)-3-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoyl]amino]-3-phenylpropanoate
  参考文献：
  名称：

  Design, Synthesis, Molecular Modeling Studies, and Calpain Inhibitory Activity of Novel α-Ketoamides Incorporating Polar Residues at the P₁‘-Position

  摘要：

  A series of novel alpha-ketoamides incorporating stereoisomeric residues with different electronic properties at the P-1'-position were synthesized to study the electronic requirements for inhibitor binding to the S-1'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. For example, ester la (CbZ-L-Leu-L-Phe-CO-D-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative 2a (Cbz-L-Leu-L-Phe-CO-D-Phe-OH). Additionally, amidino derivative 3a (CbZ-L-Leu-L-Phe-CONH-D-CH[C(NH)NH2]Bn) was about 6000-fold more potent than 2a. Furthermore, 4a (Cbz-L-Leu-L-Phe-CONHCH2Bn) was 12-fold less potent than its aza analogue 4b (CbZ-L-Leu-L-Phe-CONHNHBn). The results are consistent with the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. The acidic amino acid residue was found to be Glu261 via molecular modeling studies.

  DOI：

  10.1021/jm0301336

文献信息

• Design, Synthesis, Molecular Modeling Studies, and Calpain Inhibitory Activity of Novel α-Ketoamides Incorporating Polar Residues at the P₁‘-Position
  作者：Isaac O. Donkor、Jie Han、Xiaozhang Zheng

  DOI：10.1021/jm0301336

  日期：2004.1.1

  A series of novel alpha-ketoamides incorporating stereoisomeric residues with different electronic properties at the P-1'-position were synthesized to study the electronic requirements for inhibitor binding to the S-1'-subsite of calpain I. The results of the study suggested the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. For example, ester la (CbZ-L-Leu-L-Phe-CO-D-Phe-OMe) was over 450-fold more potent than its carboxylic acid derivative 2a (Cbz-L-Leu-L-Phe-CO-D-Phe-OH). Additionally, amidino derivative 3a (CbZ-L-Leu-L-Phe-CONH-D-CH[C(NH)NH2]Bn) was about 6000-fold more potent than 2a. Furthermore, 4a (Cbz-L-Leu-L-Phe-CONHCH2Bn) was 12-fold less potent than its aza analogue 4b (CbZ-L-Leu-L-Phe-CONHNHBn). The results are consistent with the presence of an acidic amino acid residue at the S-1'-subsite of calpain I. The acidic amino acid residue was found to be Glu261 via molecular modeling studies.