N-(6-hydrazino-pyrimidin-4-yl)-N,N-dimethyl-ethane-1,2-diamine | 700803-94-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(6-hydrazino-pyrimidin-4-yl)-N,N-dimethyl-ethane-1,2-diamine
• 英文别名: N-(6-hydrazinylpyrimidin-4-yl)-N',N'-dimethylethane-1,2-diamine
• CAS: 700803-94-7
• 化学式: C₈H₁₆N₆
• 分子量: 196.255
• InChiKey: KPEOOCJRQMIWPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.1
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(6-hydrazino-pyrimidin-4-yl)-N,N-dimethyl-ethane-1,2-diamine 、 phenyl N'-cyano-N-(2-methoxyphenyl)carbamimidate 生成 1-[6-(2-dimethylamino-ethylamino)-pyrimidin-4-yl]-N3-(2-methoxy-phenyl)-1H-[1,2,4]triazole-3,5-diamine
  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

文献信息

• DIAMINOTRIAZOLES USEFUL AS INHIBITORS OF PROTEIN KINASES
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1562589B1

  公开（公告）日：2009-01-07
• 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
  作者：Robert J. Davies、Albert C. Pierce、Cornelia Forster、Ron Grey、Jinwang Xu、Michael Arnost、Deborah Choquette、Vincent Galullo、Shi-Kai Tian、Greg Henkel、Guanjing Chen、David K. Heidary、Joanne Ma、Cameron Stuver-Moody、Mark Namchuk

  DOI：10.1021/jm200712h

  日期：2011.10.27

  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.