2(R)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-1-amidino-3-phenylpropane | 648433-94-7

• 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: 2(R)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-1-amidino-3-phenylpropane
• CAS: 648433-94-7
• 化学式: C₃₃H₄₁N₅O₅
• 分子量: 587.719
• InChiKey: HOBLCTKLZUASOF-ALPTWIEUSA-N

物化性质

• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 重原子数：
  43.0
• 可旋转键数：
  15.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  166.63
• 氢给体数：
  6.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  2(R)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-1-amidino-3-phenylpropane 在 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 甲苯 为溶剂， 反应 2.0h， 以60%的产率得到benzyl N-[(2S)-1-[[(2S)-4-[[(2R)-1-amino-1-imino-3-phenylpropan-2-yl]amino]-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
  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(R)-[3(S)-(N-tert-butyloxycarbonylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-3-phenylpropionitrile 在 N-甲基吗啉 、 N-乙酰基-L-半胱氨酸 、 ammonium acetate 、 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 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 2(R)-[3(S)-(N-Cbz-L-leucylamino)-2(R,S)-hydroxy-4-phenylbutyrylamino]-1-amidino-3-phenylpropane
  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