(S)-E-3-ethoxycarbonyl-N-<(1-benzyloxycarbonyl)-phenethyl>acrylamide

• 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: (S)-E-3-ethoxycarbonyl-N-<(1-benzyloxycarbonyl)-phenethyl>acrylamide
• 英文别名: (S,E)-3-(1-benzyloxycarbonyl-2-phenylethylcarbamoyl)-acrylic acid ethyl ester；(S,E)-3-((S)-1-Benzyloxycarbonyl-2-phenylethylcarbamoyl)-acrylic acid ethyl ester；ethyl (E)-4-oxo-4-[[(2S)-1-oxo-3-phenyl-1-phenylmethoxypropan-2-yl]amino]but-2-enoate
• 化学式: C₂₂H₂₃NO₅
• 分子量: 381.428
• InChiKey: BABVEBNJYXWYQX-KQDNUWKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  富马酸单乙酯 、 3-苯基-L-丙氨酸苄酯 在 N-甲基吗啉 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-E-3-ethoxycarbonyl-N-<(1-benzyloxycarbonyl)-phenethyl>acrylamide
  参考文献：
  名称：

  Michael Acceptor Based Antiplasmodial and Antitrypanosomal Cysteine Protease Inhibitors with Unusual Amino Acids

  摘要：

  New peptidic Michael acceptor based cysteine protease inhibitors displaying antiparasitic activity were identified by testing a broad series of 45 compounds in total, containing Asn, Gln, or Phe. As target enzymes, falcipain-2 and -3 from P. falciparum and rhodesain from T. b. rhodesiense were used. In the case of the Asn/Gln containing compounds, the trityl-protected, diastereomeric E-configured vinylogous dipeptide esters 16 (Boc-(S)-Phg-(R/S)-vGln(Trt)-OEt) were discovered as most active inhibitors concerning both protease inhibition and antiparasitic acitivity, with inhibition constants in the submicromolar range. The Compounds were shown to display time-dependent and competitive inhibition. In the case of the Phe containing Compounds, the maleic acid derivatives 42 and 43 (BnO-Phe <- Mal-Phe-OBn, BnO-Phe <- Mal-Phe-Ala-OBn. Mal = maleic acid) displayed good inhibition of rhodesain as well as good antitrypanosomal activity, while the fumaric acid derived E-analogue 14 (BnO-Phe <- Fum-Phe-OBn) only displayed inhibition or the target enzymes but no antiparasitic activity. Inhibition by these Phe derivatives was shown to be time-independent and competitive.

  DOI：

  10.1021/jm900946n

文献信息

• Aziridine-2,3-dicarboxylic Acid Derivatives as Inhibitors of Papain
  作者：Tanja Schirmeister

  DOI：10.1002/ardp.19963290504

  日期：——

  Aziridine‐2,3‐dicarboxylates and N‐acylated derivatives have been evaluated as potential irreversible inhibitors of the cysteine proteinase papain. Dependence of inhibition activity on stereo‐chemistry of the aziridine moiety has been analyzed. Whereas unsubstituted (R,R)‐ and (S,S)‐ diethyl aziridine‐2,3‐dicarboxylates (5) and (2) show no significant difference in inactivation the derivative acylated

  Aziridine-2,3-dicarboxylates 和 N-acylated 衍生物已被评估为半胱氨酸蛋白酶木瓜蛋白酶的潜在不可逆抑制剂。已经分析了抑制活性对氮丙啶部分立体化学的依赖性。而未取代的 (R,R)- 和 (S,S)- 二乙基氮丙啶-2,3-二羧酸酯 (5) 和 (2) 在钝化 BOC-(S)-Phe (BOC- (S)-Phe-(S,S)-Azi) (10) 的活性比非对映异构体 BOC-(S)-Phe-(R,R)-Azi (11) 高 6 倍。用 Z- 或 BOC-(S)-Ala (9, 8) 酰化的类似物具有较低的二级速率常数，表明抑制剂的氨基酸部分与酶的 S2 亚位点结合。
• Michael Acceptor Based Antiplasmodial and Antitrypanosomal Cysteine Protease Inhibitors with Unusual Amino Acids
  作者：Alexander Breuning、Björn Degel、Franziska Schulz、Christian Büchold、Martin Stempka、Uwe Machon、Saskia Heppner、Christoph Gelhaus、Matthias Leippe、Matthias Leyh、Caroline Kisker、Jennifer Rath、August Stich、Jiri Gut、Philip J. Rosenthal、Carsten Schmuck、Tanja Schirmeister

  DOI：10.1021/jm900946n

  日期：2010.3.11

  New peptidic Michael acceptor based cysteine protease inhibitors displaying antiparasitic activity were identified by testing a broad series of 45 compounds in total, containing Asn, Gln, or Phe. As target enzymes, falcipain-2 and -3 from P. falciparum and rhodesain from T. b. rhodesiense were used. In the case of the Asn/Gln containing compounds, the trityl-protected, diastereomeric E-configured vinylogous dipeptide esters 16 (Boc-(S)-Phg-(R/S)-vGln(Trt)-OEt) were discovered as most active inhibitors concerning both protease inhibition and antiparasitic acitivity, with inhibition constants in the submicromolar range. The Compounds were shown to display time-dependent and competitive inhibition. In the case of the Phe containing Compounds, the maleic acid derivatives 42 and 43 (BnO-Phe <- Mal-Phe-OBn, BnO-Phe <- Mal-Phe-Ala-OBn. Mal = maleic acid) displayed good inhibition of rhodesain as well as good antitrypanosomal activity, while the fumaric acid derived E-analogue 14 (BnO-Phe <- Fum-Phe-OBn) only displayed inhibition or the target enzymes but no antiparasitic activity. Inhibition by these Phe derivatives was shown to be time-independent and competitive.