Phosphoric acid mono-(4-{(S)-2-acetylamino-2-[(S)-1-(3-benzyl-[1,2,4]oxadiazol-5-yl)-3-carbamoyl-propylcarbamoyl]-ethyl}-phenyl) ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: Phosphoric acid mono-(4-{(S)-2-acetylamino-2-[(S)-1-(3-benzyl-[1,2,4]oxadiazol-5-yl)-3-carbamoyl-propylcarbamoyl]-ethyl}-phenyl) ester
• 英文别名: 4-[(2S)-2-{[(1S)-1-(3-benzyl-1,2,4-oxadiazol-5-yl)-3-carbamoylpropyl]carbamoyl}-2-acetamidoethyl]phenoxyphosphonic acid；[4-[(2S)-2-acetamido-3-[[(1S)-4-amino-1-(3-benzyl-1,2,4-oxadiazol-5-yl)-4-oxobutyl]amino]-3-oxopropyl]phenyl] dihydrogen phosphate
• 化学式: C₂₄H₂₈N₅O₈P
• 分子量: 545.489
• InChiKey: QORDHESRPJEYMQ-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  207
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  [(S)-1-(3-Benzyl-[1,2,4]oxadiazol-5-yl)-3-carbamoyl-propyl]-carbamic acid tert-butyl ester 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.5h， 生成 Phosphoric acid mono-(4-{(S)-2-acetylamino-2-[(S)-1-(3-benzyl-[1,2,4]oxadiazol-5-yl)-3-carbamoyl-propylcarbamoyl]-ethyl}-phenyl) ester
  参考文献：
  名称：

  Discovery of Potent and Selective SH2 Inhibitors of the Tyrosine Kinase ZAP-70

  摘要：

  A series of 1,2,4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200-400-fold more potent than the native, monophosphorylated tetrapeptide sequences. When compared with the high-affinity xi-1-ITAM peptide (Ac-NQL-pYNELNLGRREE-pYDVLD-NH2, wherein pY refers to phosphotyrosine) some of the best 1,2,4-oxadiazole analogues are approximately 1 order of magnitude less active. This series of compounds displays an unprecedented level of selectivity over the closely related tyrosine kinase Syk, as well as other SH2-containing proteins such as Src and Grb2. Gel shift studies using a protein construct consisting only of C-terminal ZAP-70 SH2 demonstrate that these compounds can effectively engage this particular SH2 domain.

  DOI：

  10.1021/jm990229t

文献信息

• Discovery of Potent and Selective SH2 Inhibitors of the Tyrosine Kinase ZAP-70
  作者：Chi B. Vu、Evelyn G. Corpuz、Taylor J. Merry、Selvaluxmi G. Pradeepan、Catherine Bartlett、Regine S. Bohacek、Martyn C. Botfield、Charles J. Eyermann、Berkley A. Lynch、Ian A. MacNeil、Mary K. Ram、Marie Rose van Schravendijk、Shelia Violette、Tomi K. Sawyer

  DOI：10.1021/jm990229t

  日期：1999.10.1

  A series of 1,2,4-oxadiazole analogues has been shown to be potent and selective SH2 inhibitors of the tyrosine kinase ZAP-70, a potential therapeutic target for immune suppression. These compounds typically are 200-400-fold more potent than the native, monophosphorylated tetrapeptide sequences. When compared with the high-affinity xi-1-ITAM peptide (Ac-NQL-pYNELNLGRREE-pYDVLD-NH2, wherein pY refers to phosphotyrosine) some of the best 1,2,4-oxadiazole analogues are approximately 1 order of magnitude less active. This series of compounds displays an unprecedented level of selectivity over the closely related tyrosine kinase Syk, as well as other SH2-containing proteins such as Src and Grb2. Gel shift studies using a protein construct consisting only of C-terminal ZAP-70 SH2 demonstrate that these compounds can effectively engage this particular SH2 domain.