(2S)-3-[3,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid | 213757-63-2

• 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: (2S)-3-[3,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 213757-63-2
• 化学式: C₃₆H₄₁NO₁₀
• 分子量: 647.722
• InChiKey: GXJRKJXSUHSIRG-NDEPHWFRSA-N

物化性质

• 沸点：
  767.2±60.0 °C(Predicted)
• 密度：
  1.237±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  47
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  147
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (2S)-3-[3,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid 、 (2S)-2-amino-N1-[3-(1-naphthalenyl)propyl]butanediamide 在 N,N′-二叔丁基碳二亚胺 、 1-羟基苯并三唑 作用下， 生成 {2-tert-Butoxycarbonylmethoxy-5-[(S)-2-{1-[(S)-2-carbamoyl-1-(3-naphthalen-1-yl-propylcarbamoyl)-ethylcarbamoyl]-cyclohexylcarbamoyl}-2-(9H-fluoren-9-ylmethoxycarbonylamino)-ethyl]-phenoxy}-acetic acid tert-butyl ester
  参考文献：
  名称：

  Potent Inhibition of Grb2 SH2 Domain Binding by Non-Phosphate-Containing Ligands

  摘要：

  Development of Grb2 Src homology 2 (SH2) domain binding inhibitors has important implications for treatment of a variety of diseases, including several cancers. In cellular studies, inhibitors of Grb2 SH2 domain binding have to date been large, highly charged peptides which relied on special transport devices for cell membrane penetration. Work presented in the current study examines a variety of pTyr mimetics in the context of a high-affinity Grb2 binding platform. Among the analogues studied are new norm-phosphorus-containing pTyr mimetics 23a and 23b which, when incorporated into tripeptide structures 18f and 20f, are able to inhibit Grb2 SH2 domain binding with affinities among the best yet reported for non-phosphorus-containing SH2 domain inhibitors (IC50 values of 6.7 and 1.3 mu M, respectively). The present study has also demonstrated the usefulness of the Na-oxalyl group as an auxiliary which enhances the binding potency of both phosphorus- and non-phosphorus-containing pTyr mimetics. When combined with the (phosphonomethyl)phenylalanine (Pmp) residue to give analogues such as L-20d, potent inhibition of Grb2 SH2 domain binding can be achieved both in extracellular assays using isolated Grb2 SH2 domain protein and in intracellular systems measuring the association of endogenous Grb2 with its cognate p185(erbB-2) ligand. These latter effects can be achieved at micromolar to submicromolar concentrations without prodrug derivatization. The oxalyl-containing pTyr mimetics presented in this study should be of general usefulness for the development of other Grb2 SH2 domain antagonists, independent of the beta-bend-mimicking platform utilized for their display.

  DOI：

  10.1021/jm980388x
• 作为产物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 (2S)-2-amino-3-[3,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic acid 在 碳酸氢钠 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以68%的产率得到(2S)-3-[3,4-bis[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
  参考文献：
  名称：

  非含磷磷酸酪氨酸模拟物的对映选择性合成及其在酪氨酸磷酸酶抑制肽制备中的应用

  摘要：

  三个新的L-氨基酸类似物12,18和25都在适于掺入到通过使用Fmoc协议固相合成肽保护形式被制备。这些试剂代表不含磷的磷酸酪氨酰基（pTyr）模拟物，其利用羧基提供通常由pTyr磷酸基团提供的官能度。为了证明这些类似物的效用，制备了模拟酪氨酸的蛋白酪氨酸磷酸酶定向肽Ac-DADE- X -L-酰胺（28-30）。在（8）a K i的情况下针对PTP1的取值为3.6μM，等于母体含pTyr的肽的Km。除了酪氨酸磷酸酶，这些类似物在许多情况下可能有用，包括SH2结构域和磷酸酪氨酸结合结构域系统。

  DOI：

  10.1016/s0040-4020(98)00590-0