N-(4-methoxy-1,4-dioxobutyl)-L-valyl-N-<3,3,3-trifluoro-2-hydroxy-1-(phenylmethyl)propyl>-L-prolinamide | 123206-15-5

• 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: N-(4-methoxy-1,4-dioxobutyl)-L-valyl-N-<3,3,3-trifluoro-2-hydroxy-1-(phenylmethyl)propyl>-L-prolinamide
• 英文别名: methyl 4-[[(2S)-3-methyl-1-oxo-1-[(2S)-2-[(4,4,4-trifluoro-3-hydroxy-1-phenylbutan-2-yl)carbamoyl]pyrrolidin-1-yl]butan-2-yl]amino]-4-oxobutanoate
• CAS: 123206-15-5
• 化学式: C₂₅H₃₄F₃N₃O₆
• 分子量: 529.557
• InChiKey: LFOYPBYCBBGXIU-RHTRQGEGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.72
• 重原子数：
  37.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  125.04
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-(4-methoxy-1,4-dioxobutyl)-L-valyl-N-<3,3,3-trifluoro-2-hydroxy-1-(phenylmethyl)propyl>-L-prolinamide 在 戴斯-马丁氧化剂 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 144.0h， 以90%的产率得到N-{(S)-1-[(S)-2-(1-Benzyl-3,3,3-trifluoro-2-oxo-propylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propyl}-succinamic acid methyl ester
  参考文献：
  名称：

  Synthesis of peptidyl fluoromethyl ketones and peptidyl .alpha.-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G

  摘要：

  Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.

  DOI：

  10.1021/jm00163a063
• 作为产物：
  描述：

  N-Boc-L-缬氨酸 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 氢气 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， -20.0~25.0 ℃ 、101.33 kPa 条件下， 反应 13.5h， 生成 N-(4-methoxy-1,4-dioxobutyl)-L-valyl-N-<3,3,3-trifluoro-2-hydroxy-1-(phenylmethyl)propyl>-L-prolinamide
  参考文献：
  名称：

  Synthesis of peptidyl fluoromethyl ketones and peptidyl .alpha.-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G

  摘要：

  Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.

  DOI：

  10.1021/jm00163a063

文献信息

• PEET, NORTON P.;BURKHART, JOSEPH P.;ANGELASTRO, MICHAEL R.;GIROUX, EUGENE+, J. MED. CHEM., 33,(1990) N, C. 394-407
  作者：PEET, NORTON P.、BURKHART, JOSEPH P.、ANGELASTRO, MICHAEL R.、GIROUX, EUGENE+

  DOI：——

  日期：——