2(R)-[3(S)-(N-tert-butoxycarbonylamino)-2(R,S)-hydroxy-4-phenylbutyryl-amino]-3-phenylpropionic acid methyl ester | 648433-87-8

• 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: 2(R)-[3(S)-(N-tert-butoxycarbonylamino)-2(R,S)-hydroxy-4-phenylbutyryl-amino]-3-phenylpropionic acid methyl ester
• CAS: 648433-87-8
• 化学式: C₂₅H₃₂N₂O₆
• 分子量: 456.539
• InChiKey: OMOZFVJVBJEMBY-MCOCGALXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.38
• 重原子数：
  33.0
• 可旋转键数：
  9.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  113.96
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2(R)-[3(S)-(N-tert-butoxycarbonylamino)-2(R,S)-hydroxy-4-phenylbutyryl-amino]-3-phenylpropionic acid methyl ester 在 N-甲基吗啉 、 盐酸 、 sodium hydroxide 、 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 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (2R)-2-[[(3S)-3-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoyl]amino]-3-phenylpropanoic acid
  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：

  D-苯丙氨酸甲酯盐酸盐 、 (2RS,3S)-3-叔丁氧羰酰氨基-2-羟基-4-苯丁酸, 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以87%的产率得到2(R)-[3(S)-(N-tert-butoxycarbonylamino)-2(R,S)-hydroxy-4-phenylbutyryl-amino]-3-phenylpropionic acid methyl ester
  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