methyl (2S,3S)-2-[[2-[3,5-bis[[bis(pyridin-2-ylmethyl)amino]methyl]phenyl]benzoyl]amino]-3-methylpentanoate | 1391730-71-4

• 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: methyl (2S,3S)-2-[[2-[3,5-bis[[bis(pyridin-2-ylmethyl)amino]methyl]phenyl]benzoyl]amino]-3-methylpentanoate
• CAS: 1391730-71-4
• 化学式: C₄₆H₄₉N₇O₃
• 分子量: 747.94
• InChiKey: MUASBKFMRJRDOI-HPEARGQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  56
• 可旋转键数：
  19
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(甲氧基羰基)苯硼酸 在 Pd(PPh₃)3Cl 、 水 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 methyl (2S,3S)-2-[[2-[3,5-bis[[bis(pyridin-2-ylmethyl)amino]methyl]phenyl]benzoyl]amino]-3-methylpentanoate
  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

文献信息

• Phosphopeptide Selective Coordination Complexes as Promising Src Homology 2 Domain Mimetics
  作者：Joel A. Drewry、Eugenia Duodu、Amir Mazouchi、Paul Spagnuolo、Steven Burger、Claudiu C. Gradinaru、Paul Ayers、Aaron D. Schimmer、Patrick T. Gunning

  DOI：10.1021/ic3008393

  日期：2012.8.6

  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.