2(S)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-3-phenylpropionitrile | 648433-97-0

• 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(S)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-3-phenylpropionitrile
• 英文别名: benzyl N-[(2S)-1-[[(2S)-4-[[(1S)-1-cyano-2-phenylethyl]amino]-3-hydroxy-4-oxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
• CAS: 648433-97-0
• 化学式: C₃₃H₃₈N₄O₅
• 分子量: 570.689
• InChiKey: VFVKCOPDKFKRFV-UNVCSADESA-N

物化性质

• 沸点：
  879.7±65.0 °C(Predicted)
• 密度：
  1.200±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  42.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  140.55
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2(S)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-3-phenylpropionitrile 在 N-乙酰基-L-半胱氨酸 、 ammonium acetate 、 三氟乙酸吡啶 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 18.0h， 生成 {(S)-1-[(S)-1-Benzyl-2-((S)-1-carbamimidoyl-2-phenyl-ethylcarbamoyl)-2-oxo-ethylcarbamoyl]-3-methyl-butyl}-carbamic acid benzyl 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
• 作为产物：
  描述：

  2(S)-[3(S)-(N-tert-butyloxycarbonylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-3-phenylpropionitrile 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 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2(S)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-3-phenylpropionitrile
  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