| 700805-02-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• CAS: 700805-02-3
• 化学式: C₁₉H₂₀N₄O₃
• 分子量: 352.393
• InChiKey: SBNNPQVYKFYIKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  26.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  79.11
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  6-肼基烟腈 、 生成 6-[5-amino-3-(2-methoxy-4-morpholin-4-yl-phenylamino)-[1,2,4]triazol-1-yl]-nicotinonitrile
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Novel Dual Fms-Like Tyrosine Kinase 3/Stem Cell Factor Receptor (FLT3/c-KIT) Inhibitor for the Treatment of Acute Myelogenous Leukemia

  摘要：

  A high-throughput screen of our compound archive revealed a novel class of dual FMS-like tyrosine kinase 3 (FLT3)/c-KIT inhibitors. With the help of molecular modeling, this class was rapidly optimized for both potency against FLT3 and FLT3/c-KIT and excellent potency in cell-based assays, leading to dose-dependent cell death in acute myelogenous leukemia (AML) patient blast samples. Ultimately, the AML patient blast data defined the preferred target profile as we designed and evaluated a set of FLT3 selective and FLT3/c-KIT dual molecules. Further optimization for pharmacokinetic properties resulted in the selection of the dual FLT3/c-KIT inhibitor, N-3-(4-(trans-4-morpholinocyclohexyl)phenyl)-1-(pyridin-2-yl)-1H-1,2,4-triazole-3,5-diamine, VX-322 (compound 37), to move forward to preclinical evaluation.

  DOI：

  10.1021/jm200712h
• 作为产物：
  描述：

  2-甲氧基-4-(4-吗啉)苯胺 、 N-氰基羰亚胺二苯基酯 以 异丙醇 为溶剂， 生成
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of a Novel Dual Fms-Like Tyrosine Kinase 3/Stem Cell Factor Receptor (FLT3/c-KIT) Inhibitor for the Treatment of Acute Myelogenous Leukemia

  摘要：

  A high-throughput screen of our compound archive revealed a novel class of dual FMS-like tyrosine kinase 3 (FLT3)/c-KIT inhibitors. With the help of molecular modeling, this class was rapidly optimized for both potency against FLT3 and FLT3/c-KIT and excellent potency in cell-based assays, leading to dose-dependent cell death in acute myelogenous leukemia (AML) patient blast samples. Ultimately, the AML patient blast data defined the preferred target profile as we designed and evaluated a set of FLT3 selective and FLT3/c-KIT dual molecules. Further optimization for pharmacokinetic properties resulted in the selection of the dual FLT3/c-KIT inhibitor, N-3-(4-(trans-4-morpholinocyclohexyl)phenyl)-1-(pyridin-2-yl)-1H-1,2,4-triazole-3,5-diamine, VX-322 (compound 37), to move forward to preclinical evaluation.

  DOI：

  10.1021/jm200712h