N-acetyl-L-prolyl-L-alanyl-N-(3,3,3-trifluoro-2-hydroxy-1-methylpropyl)-L-prolinamide | 106771-14-6

• 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-acetyl-L-prolyl-L-alanyl-N-(3,3,3-trifluoro-2-hydroxy-1-methylpropyl)-L-prolinamide
• 英文别名: 1,1,1-Trifluoro-3-[(N-acetylprolyl)alanylprolylamino]butan-2-ol；(2S)-1-acetyl-N-[(2S)-1-oxo-1-[(2S)-2-[(4,4,4-trifluoro-3-hydroxybutan-2-yl)carbamoyl]pyrrolidin-1-yl]propan-2-yl]pyrrolidine-2-carboxamide
• CAS: 106771-14-6
• 化学式: C₁₉H₂₉F₃N₄O₅
• 分子量: 450.458
• InChiKey: LUSDYNAOIYFKSH-CNQRTRDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-acetyl-L-prolyl-L-alanyl-N-(3,3,3-trifluoro-2-hydroxy-1-methylpropyl)-L-prolinamide 在 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以30%的产率得到(2S)-1-acetyl-N-[(2S)-1-oxo-1-[(2S)-2-[(4,4,4-trifluoro-3-oxobutan-2-yl)carbamoyl]pyrrolidin-1-yl]propan-2-yl]pyrrolidine-2-carboxamide
  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：

  Acetyl-L-prolyl-L-alanyl-L-proline 在 N-甲基吗啉 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 4.17h， 生成 N-acetyl-L-prolyl-L-alanyl-N-(3,3,3-trifluoro-2-hydroxy-1-methylpropyl)-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

• Peptidase inhibitors
  申请人：Merrell Pharmaceuticals Inc.

  公开号：US05496927A1

  公开（公告）日：1996-03-05

  This invention relates to analogs of peptidase substrates in which the amide group containing the scissile amide bond of the substrate peptide has been replaced by an activated electrophilic ketone moiety. These analogs of the peptidase substrates provide specific enzyme inhibitors for a variety of proteases, the inhibition of which will have useful physiological consequences in a variety of disease states.

  本发明涉及肽酶底物的类似物，其中底物肽的含有可切割酰胺键的酰胺基团已被活化的亲电性酮基团替换。这些肽酶底物的类似物为各种蛋白酶提供了特异性的酶抑制剂，抑制这些蛋白酶将在各种疾病状态下产生有用的生理后果。
• 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：——
• Novel peptidase inhibitors
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0195212B1

  公开（公告）日：1993-11-24
• US5496927A
  申请人：——

  公开号：US5496927A

  公开（公告）日：1996-03-05
• US6130315A
  申请人：——

  公开号：US6130315A

  公开（公告）日：2000-10-10