(S)-4-Amino-4-(3-naphthalen-1-ylmethyl-[1,2,4]oxadiazol-5-yl)-butyramide | 1054668-23-3

• 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)-4-Amino-4-(3-naphthalen-1-ylmethyl-[1,2,4]oxadiazol-5-yl)-butyramide
• 英文别名: (4S)-4-amino-4-[3-(naphthalen-1-ylmethyl)-1,2,4-oxadiazol-5-yl]butanamide
• CAS: 1054668-23-3
• 化学式: C₁₇H₁₈N₄O₂
• 分子量: 310.356
• InChiKey: BVLJTDFJZVYYNW-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-4-Amino-4-(3-naphthalen-1-ylmethyl-[1,2,4]oxadiazol-5-yl)-butyramide 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 8.5h， 生成 Phosphoric acid mono-(4-{(S)-2-acetylamino-2-[(S)-3-carbamoyl-1-(3-naphthalen-1-ylmethyl-[1,2,4]oxadiazol-5-yl)-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
• 作为产物：
  描述：

  1-萘乙腈 在 吡啶 、 sodium hydroxide 、 盐酸羟胺 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 66.5h， 生成 (S)-4-Amino-4-(3-naphthalen-1-ylmethyl-[1,2,4]oxadiazol-5-yl)-butyramide
  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