Acetyl-L-prolyl-L-alanyl-L-proline | 41036-61-7

• 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: Acetyl-L-prolyl-L-alanyl-L-proline
• 英文别名: Acetylprolylalanylproline；(2S)-1-[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]propanoyl]pyrrolidine-2-carboxylic acid
• CAS: 41036-61-7
• 化学式: C₁₅H₂₃N₃O₅
• 分子量: 325.365
• InChiKey: CMFZCVLZQZQFEM-DLOVCJGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Acetyl-L-prolyl-L-alanyl-L-proline 在 N-甲基吗啉 、 草酰氯 、 二甲基亚砜 作用下， 以 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 3.09h， 生成 N-acetyl-L-prolyl-L-alanyl-N-(3-methoxy-1-methyl-2,3-dioxopropyl)-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

• Peptide carbazates and pharmaceutical composition
  申请人：Merck & Co., Inc.

  公开号：US04064236A1

  公开（公告）日：1977-12-20

  Certain novel peptide carbazates, their preparation, pharmaceutical compositions and novel methods of treating pancreatitis.

  某些新型肽类卡巴曲酰胺、它们的制备、制药组合物和治疗胰腺炎的新方法。
• Novel peptidase inhibitors
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0195212A2

  公开（公告）日：1986-09-24

  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，在这些类似物中，含有底物肽的巯基酰胺键的酰胺基团已被活化的亲电酮分子取代。这些肽酶底物类似物为多种蛋白酶提供了特异性酶抑制剂，其抑制作用将对多种疾病产生有益的生理影响。
• 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：——
• US4064236A
  申请人：——

  公开号：US4064236A

  公开（公告）日：1977-12-20
• US5496927A
  申请人：——

  公开号：US5496927A

  公开（公告）日：1996-03-05