(S)-benzyl-2-{(Z)-3-[(S)-1-((S)-1-benzyloxycarbonylethyl-carbamoyl)-2-phenylethylcarbamoyl]acryloylamino}-3-phenylpropionate | 1207718-83-9

• 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)-benzyl-2-{(Z)-3-[(S)-1-((S)-1-benzyloxycarbonylethyl-carbamoyl)-2-phenylethylcarbamoyl]acryloylamino}-3-phenylpropionate
• 英文别名: benzyl (2S)-2-[[(Z)-4-oxo-4-[[(2S)-1-oxo-1-[[(2S)-1-oxo-1-phenylmethoxypropan-2-yl]amino]-3-phenylpropan-2-yl]amino]but-2-enoyl]amino]-3-phenylpropanoate
• CAS: 1207718-83-9
• 化学式: C₃₉H₃₉N₃O₇
• 分子量: 661.755
• InChiKey: JSSLVLBSWUOXKH-BQEBWFSCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  49
• 可旋转键数：
  18
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (Z)-3-((S)-1-benzyloxycarbonyl-2-phenylethylcarbamoyl)acrylic acid 、 TFA*Phe-Ala-OBz 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以40%的产率得到(S)-benzyl-2-{(Z)-3-[(S)-1-((S)-1-benzyloxycarbonylethyl-carbamoyl)-2-phenylethylcarbamoyl]acryloylamino}-3-phenylpropionate
  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