3-(3-(4-(2-aminopyrimidin-4-yl)phenyl)ureido)-N-isopropylbenzamide | 1361414-23-4

• 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: 3-(3-(4-(2-aminopyrimidin-4-yl)phenyl)ureido)-N-isopropylbenzamide
• 英文别名: 3-[[4-(2-aminopyrimidin-4-yl)phenyl]carbamoylamino]-N-propan-2-ylbenzamide
• CAS: 1361414-23-4
• 化学式: C₂₁H₂₂N₆O₂
• 分子量: 390.445
• InChiKey: UOJBZXDYIJDUAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  122
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-(3-(4-bromophenyl)ureido)-N-isopropylbenzamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 四(三苯基膦)钯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 生成 3-(3-(4-(2-aminopyrimidin-4-yl)phenyl)ureido)-N-isopropylbenzamide
  参考文献：
  名称：

  Bis-aryl Urea Derivatives as Potent and Selective LIM Kinase (Limk) Inhibitors

  摘要：

  The discovery/optimization of bis-aryl ureas as Limk inhibitors to obtain high potency and selectivity and appropriate pharmacokinetic properties through systematic SAR studies is reported. Docking studies supported the observed SAR. Optimized Limk inhibitors had high biochemical potency (IC50 < 25 nM), excellent selectivity against ROCK and JNK kinases (>400-fold), potent inhibition of cofilin phosphorylation in A7r5, PC-3, and CEM-SS T cells (IC50 < 1 mu M), and good in vitro and in vivo pharmacokinetic properties. In the profiling against a panel of 61 kinases, compound 18b at 1 mu M inhibited only Limk1 and STK16 with >= 80% inhibition. Compounds 18b and 18f were highly efficient in inhibiting cell-invasion/migration in PC-3 cells. In addition, compound 18w was demonstrated to be effective on reducing intraocular pressure (IOP) on rat eyes. Taken together, these data demonstrated that we had developed a novel class of bis-aryl urea derived potent and selective Limk inhibitors.

  DOI：

  10.1021/jm501680m

文献信息

• Bis-aryl Urea Derivatives as Potent and Selective LIM Kinase (Limk) Inhibitors
  作者：Yan Yin、Ke Zheng、Nibal Eid、Shannon Howard、Ji-Hak Jeong、Fei Yi、Jia Guo、Chul Min Park、Mathieu Bibian、Weilin Wu、Pamela Hernandez、HaJeung Park、Yuntao Wu、Jun-Li Luo、Philip V. LoGrasso、Yangbo Feng

  DOI：10.1021/jm501680m

  日期：2015.2.26

  The discovery/optimization of bis-aryl ureas as Limk inhibitors to obtain high potency and selectivity and appropriate pharmacokinetic properties through systematic SAR studies is reported. Docking studies supported the observed SAR. Optimized Limk inhibitors had high biochemical potency (IC50 < 25 nM), excellent selectivity against ROCK and JNK kinases (>400-fold), potent inhibition of cofilin phosphorylation in A7r5, PC-3, and CEM-SS T cells (IC50 < 1 mu M), and good in vitro and in vivo pharmacokinetic properties. In the profiling against a panel of 61 kinases, compound 18b at 1 mu M inhibited only Limk1 and STK16 with >= 80% inhibition. Compounds 18b and 18f were highly efficient in inhibiting cell-invasion/migration in PC-3 cells. In addition, compound 18w was demonstrated to be effective on reducing intraocular pressure (IOP) on rat eyes. Taken together, these data demonstrated that we had developed a novel class of bis-aryl urea derived potent and selective Limk inhibitors.