N-((3-(5-cyano-1H-benzo[d]imidazol-2-yl)phenyl)carbamothioyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: N-((3-(5-cyano-1H-benzo[d]imidazol-2-yl)phenyl)carbamothioyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide
• 英文别名: N-[[3-(6-cyano-1H-benzimidazol-2-yl)phenyl]carbamothioyl]-2,3-dihydro-1,4-benzodioxine-6-carboxamide
• 化学式: C₂₄H₁₇N₅O₃S
• 分子量: 455.497
• InChiKey: WFYIPYKZYOOKTO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  144
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-二氨基苯甲腈 在 sodium meta bi sulfate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.0h， 生成 N-((3-(5-cyano-1H-benzo[d]imidazol-2-yl)phenyl)carbamothioyl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of non-peptidic antagonists of neuropilin-1 receptor

  摘要：

  Neuropilins (NRPs) are VEGF-A165 co-receptors over-expressed in tumor cells, and considered as targets in angiogenic-related pathologies. We previously identified compound 1, the first non-peptidic antagonist of the VEGF-A165/NRP binding, which exhibits in vivo anti-angiogenic and anti-tumor activities. We report here the synthesis and biological evaluations of new antagonists structurally-related to compound 1. Among these molecules, 4a, 4c and 4d show cytotoxic effects on HUVEC and MDA-MB-31 cells, and antagonize VEGF-A165/NRP-1 binding. This study confirmed our key structure-activity relationships hypothesis and paved the way to compound 1 'hit to lead' optimization.

  DOI：

  10.1016/j.bmcl.2014.07.028