1-(4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]-pyrimidin-1-yl)cyclohexyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea

• 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: 1-(4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]-pyrimidin-1-yl)cyclohexyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea
• 英文别名: 1-[4-[4-Amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea；1-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea
• 化学式: C₃₁H₃₄N₈O₃
• 分子量: 566.663
• InChiKey: BKBRUAOLKCXWDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  146
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(4-aminocyclohexyl)-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 1-(4-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]-pyrimidin-1-yl)cyclohexyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea
  参考文献：
  名称：

  Discovery of 1-(4-(4-Amino-3-(4-(2-morpholinoethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea (CHMFL-FLT3-213) as a Highly Potent Type II FLT3 Kinase Inhibitor Capable of Overcoming a Variety of FLT3 Kinase Mutants in FLT3-ITD Positive AML

  摘要：

  FLT3-ITD mutant has been observed in about 30% of AML patients and extensively studied as a drug discovery target. On the basis of our previous study that ibrutinib (9) exhibited selective and moderate inhibitory activity against FLT3-ITD positive AML cells, through a structure-guided drug design approach, we have discovered a new type II FLT3 kinase inhibitor, compound 14 (CHMFL-FLT3-213), which exhibited highly potent inhibitory effects against FLT3TTD mutant and associated oncogenic mutations (including FLT3-D835Y/H/V, FLT3-ITD-D835Y/I/N/A/G/Del, and FLT3-ITD-F691L). In the cellular context 14 strongly affected FLT3-TTD mediated signaling pathways and induced apoptosis by arresting cell cycle into G0/G1 phase. In the in vivo studies 14 demonstrated an acceptable bioavaOability (F = 19%) and significantly suppressed the tumor growth in MV4-11 cell inoculated xenograft model (15 mg kg(-1) day(-1), TGI = 97%) without exhibiting obvious toxicity. Compound 14 might be a potential drug candidate for FLT3-TTD positive AML.

  DOI：

  10.1021/acs.jmedchem.7b00840