N-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]-N'-thiophen-3-ylurea | 935660-78-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]-N'-thiophen-3-ylurea
• 英文别名: 1-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-3-thiophen-3-ylurea
• CAS: 935660-78-9
• 化学式: C₁₇H₂₁BN₂O₃S
• 分子量: 344.242
• InChiKey: XRVUABJDVARQSZ-UHFFFAOYSA-N

物化性质

• 沸点：
  404.4±25.0 °C(predicted)
• 密度：
  1.21±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.69
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  87.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-溴噻吩并[3,2-c]吡啶-4-胺 、 N-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]-N'-thiophen-3-ylurea 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 生成 1-(4-(4-Aminothieno[3,2-c]pyridin-3-yl)phenyl)-3-(thiophen-3-yl)urea
  参考文献：
  名称：

  Thienopyridine urea inhibitors of KDR kinase

  摘要：

  A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.

  DOI：

  10.1016/j.bmcl.2006.12.015
• 作为产物：
  描述：

  3-噻吩异氰酸酯 、 4-氨基苯硼酸频哪醇酯 以 二氯甲烷 为溶剂， 生成 N-[4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)phenyl]-N'-thiophen-3-ylurea
  参考文献：
  名称：

  Discovery of N-(4-(3-Amino-1H-indazol-4-yl)phenyl)-N‘-(2-fluoro-5-methylphenyl)urea (ABT-869), a 3-Aminoindazole-Based Orally Active Multitargeted Receptor Tyrosine Kinase Inhibitor

  摘要：

  In our continued efforts to search for potent and novel receptor tyrosine kinase (RTK) inhibitors as potential anticancer agents, we discovered, through a structure-based design, that 3-aminoindazole could serve as an efficient hinge-binding template for kinase inhibitors. By incorporating an N,N'-diaryl urea moiety at the C4-position of 3-aminodazole, a series of RTK inhibitors were generated, which potently inhibited the tyrosine kinase activity of the vascular endothelial growth factor receptor and the platelet-derived growth factor receptor families. A number of compounds with potent oral activity were identified by utilizing an estradiol-induced mouse uterine edema model and an HT1080 human fibrosarcoma xenograft tumor model. In particular, compound 17p (ABT-869) was found to possess favorable pharmacokinetic profiles across different species and display significant tumor growth inhibition in multiple preclinical animal models.

  DOI：

  10.1021/jm061280h