2(R)-N-((2S)-3(RS)-hydroxy-4-oxo-4-(phenethylamino)-1-phenylbutan-2-yl)-1-(4-nitro-phenylsulfonyl)pyrrolidine-2-carboxamide | 910482-13-2

• 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: 2(R)-N-((2S)-3(RS)-hydroxy-4-oxo-4-(phenethylamino)-1-phenylbutan-2-yl)-1-(4-nitro-phenylsulfonyl)pyrrolidine-2-carboxamide
• 英文别名: Nos-D-Pro-bAla(2-OH,3S-Bn)-NHEtPh；(2R)-N-[(2S)-3-hydroxy-4-oxo-1-phenyl-4-(2-phenylethylamino)butan-2-yl]-1-(4-nitrophenyl)sulfonylpyrrolidine-2-carboxamide
• CAS: 910482-13-2
• 化学式: C₂₉H₃₂N₄O₇S
• 分子量: 580.662
• InChiKey: AZMKGSXTXCQCMZ-AJRFNQODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  170
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2(R)-N-((2S)-3(RS)-hydroxy-4-oxo-4-(phenethylamino)-1-phenylbutan-2-yl)-1-(4-nitro-phenylsulfonyl)pyrrolidine-2-carboxamide 在 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以72.5%的产率得到(2R)-N-[3,4-dioxo-1-phenyl-4-(2-phenylethylamino)butan-2-yl]-1-(4-nitrophenyl)sulfonylpyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis, Calpain Inhibitory Activity, and Cytotoxicity of P₂-Substituted Proline and Thiaproline Peptidyl Aldehydes and Peptidyl α-Ketoamides

  摘要：

  Calpain is a cytosolic cysteine endopeptidase that has been implicated in a number of disorders including cancer. We have synthesized and studied the mu-calpain inhibitory activity and cytotoxicity of peptidyl aldehydes and peptidyl alpha-ketoamides with N-substituted D-proline or L-thiaproline residues at the P-2-postion. The most potent and most selective members of the series were (R)-1-(4-nitrophenylsulfonyl)-N-((R, S)-1-oxo- 3-phenylpropan-2-yl) pyrrolidine-2-carboxamide (1j) and (R)-1-(4-iodophenylsulfonyl)-N-((R,S)-1-oxo-3- phenylpropan-2-yl) pyrrolidine-2-carboxamide (1n). The compounds inhibited A-calpain with K-i values of 0.02 mu M and 0.03 mu M, respectively, and displayed over 180-fold (1j) and 130-fold ( 1n) greater affinity for mu-calpain compared to cathepsin B. The cytotoxic effect of the compounds was evaluated in two leukemia cell lines (Daudi and Jurkat) and three solid tumor cell lines (DU-145, PC-3, and HeLa). Generally the compounds were modestly cytotoxic and displayed no correlation between the cytotoxic activity and mu-calpain inhibition.

  DOI：

  10.1021/jm050849w
• 作为产物：
  描述：

  tert-butyl 2(S)-3(RS)-hydroxy-4-oxo-4-(phenylethylamino)-1-phenylbutan-2-ylcarbamate 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 二氯甲烷 为溶剂， 反应 4.0h， 生成 2(R)-N-((2S)-3(RS)-hydroxy-4-oxo-4-(phenethylamino)-1-phenylbutan-2-yl)-1-(4-nitro-phenylsulfonyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Synthesis, Calpain Inhibitory Activity, and Cytotoxicity of P₂-Substituted Proline and Thiaproline Peptidyl Aldehydes and Peptidyl α-Ketoamides

  摘要：

  Calpain is a cytosolic cysteine endopeptidase that has been implicated in a number of disorders including cancer. We have synthesized and studied the mu-calpain inhibitory activity and cytotoxicity of peptidyl aldehydes and peptidyl alpha-ketoamides with N-substituted D-proline or L-thiaproline residues at the P-2-postion. The most potent and most selective members of the series were (R)-1-(4-nitrophenylsulfonyl)-N-((R, S)-1-oxo- 3-phenylpropan-2-yl) pyrrolidine-2-carboxamide (1j) and (R)-1-(4-iodophenylsulfonyl)-N-((R,S)-1-oxo-3- phenylpropan-2-yl) pyrrolidine-2-carboxamide (1n). The compounds inhibited A-calpain with K-i values of 0.02 mu M and 0.03 mu M, respectively, and displayed over 180-fold (1j) and 130-fold ( 1n) greater affinity for mu-calpain compared to cathepsin B. The cytotoxic effect of the compounds was evaluated in two leukemia cell lines (Daudi and Jurkat) and three solid tumor cell lines (DU-145, PC-3, and HeLa). Generally the compounds were modestly cytotoxic and displayed no correlation between the cytotoxic activity and mu-calpain inhibition.

  DOI：

  10.1021/jm050849w