5-[3,5-di(pyridin-2-yl)phenyl]-N-[5-(ethylsulfonyl)-2-methoxyphenyl]oxazol-2-amine | 1557096-51-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[3,5-di(pyridin-2-yl)phenyl]-N-[5-(ethylsulfonyl)-2-methoxyphenyl]oxazol-2-amine
• 英文别名: 5-(3,5-dipyridin-2-ylphenyl)-N-(5-ethylsulfonyl-2-methoxyphenyl)-1,3-oxazol-2-amine
• CAS: 1557096-51-1
• 化学式: C₂₈H₂₄N₄O₄S
• 分子量: 512.589
• InChiKey: HTPMEGBLXVAKBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.01
• 重原子数：
  37.0
• 可旋转键数：
  8.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  107.21
• 氢给体数：
  1.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  2-bromo-1-(3,5-dibromophenyl)ethanone 在 四(三苯基膦)钯 、 sodium azide 、 四丁基溴化铵 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 51.5h， 生成 5-[3,5-di(pyridin-2-yl)phenyl]-N-[5-(ethylsulfonyl)-2-methoxyphenyl]oxazol-2-amine
  参考文献：
  名称：

  A development of chimeric VEGFR2 TK inhibitor based on two ligand conformers from PDB: 1Y6A complex – Medicinal chemistry consequences of a TKs analysis

  摘要：

  VEGFR2 is an important mediator of angiogenesis and influences fate of some cancer stem cells. Here we analysed all 34 structures of VEGFR2 TK available from PDB database. From them a complex PDB: 1Y6A has an exceptional AAZ ligand bound to TK in form of two conformers (U- and S-shaped). This observation inspired us to develop three chimeric bispyridyl VEGFR2 inhibitors by combining structural features of both AAZ conformers and/or their relative ligand AAX (PDB: 1Y6B).Our most interesting inhibitor 22SYM has an enzymatic VEGFR2 TK activity (IC50: 15.1 nM) comparable or better to the active compounds from clinical drugs Nexavar and Sutent. 22SYM inhibits growth, migration and tube formation of endothelial cells (EC) and selectively induces EC apoptosis. 22SYM also inhibits in vivo angiogenesis in Zebrafish embryo assay.Additionally to the above results, we proved here that tyrosine kinases in an inactive form possessing Type I inhibitors can adopt both a closed or an opened conformation of kinase A-loop independently on their DFG-out arrangement. We proposed here that an activity of certain Type I inhibitors (e.g. 22SYM-like) in complex with DFG-out TK can be negatively influenced by collisions with a dynamically moving Tic A-loop. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.11.023