| 1391730-82-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• CAS: 1391730-82-7
• 化学式: C₄₀H₃₈N₆O₂
• 分子量: 634.781
• InChiKey: UIAZCBRSPNNVJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.13
• 重原子数：
  48.0
• 可旋转键数：
  14.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  84.34
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  在 水 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 methyl (2S)-2-[[2-[3,5-bis[[bis(pyridin-2-ylmethyl)amino]methyl]phenyl]benzoyl]amino]-3-phenylpropanoate
  参考文献：
  名称：

  Phosphopeptide Selective Coordination Complexes as Promising Src Homology 2 Domain Mimetics

  摘要：

  Src Homology 2 (SH2) domains are the paradigm of phosphotyrosine (pY) protein recognition modules and mediate numerous cancer-promoting protein-protein complexes. Effective SH2 domain mimicry with pY-binding coordination complexes offers a promising route to new and selective disruptors of pY-mediated protein-protein interactions. We herein report the synthesis and in vitro characterization of a library of coordination complex SH2 domain proteomimetics. Compounds were designed to interact with phosphopeptides via a two-point interaction, principally with pY, and to make secondary interactions with pY+2/3, thereby achieving sequence-selective discrimination. Here, we report that lead mimetics demonstrated high target phosphopeptide affinity (Ka similar to 10(7) W-1) and selectivity. In addition, biological screening in various tumor cells for anticancer effects showed a high degree of variability in cytotoxicity among receptors, which supported the proposed two-point binding mode. Several receptors potently disrupted cancer cell viability in breast cancer, prostate cancer, and acute myeloid leukemia cell selectivity.

  DOI：

  10.1021/ic3008393
• 作为产物：
  描述：

  5-溴异苯二醛 在 Pd(PPh₃)3Cl 、 三乙酰氧基硼氢化钠 、 potassium carbonate 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成
  参考文献：
  名称：

  Phosphopeptide Selective Coordination Complexes as Promising Src Homology 2 Domain Mimetics

  摘要：

  Src Homology 2 (SH2) domains are the paradigm of phosphotyrosine (pY) protein recognition modules and mediate numerous cancer-promoting protein-protein complexes. Effective SH2 domain mimicry with pY-binding coordination complexes offers a promising route to new and selective disruptors of pY-mediated protein-protein interactions. We herein report the synthesis and in vitro characterization of a library of coordination complex SH2 domain proteomimetics. Compounds were designed to interact with phosphopeptides via a two-point interaction, principally with pY, and to make secondary interactions with pY+2/3, thereby achieving sequence-selective discrimination. Here, we report that lead mimetics demonstrated high target phosphopeptide affinity (Ka similar to 10(7) W-1) and selectivity. In addition, biological screening in various tumor cells for anticancer effects showed a high degree of variability in cytotoxicity among receptors, which supported the proposed two-point binding mode. Several receptors potently disrupted cancer cell viability in breast cancer, prostate cancer, and acute myeloid leukemia cell selectivity.

  DOI：

  10.1021/ic3008393