N-(tert-butyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine | 956018-45-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(tert-butyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine
• CAS: 956018-45-4
• 化学式: C₁₆H₁₇FN₄
• 分子量: 284.336
• InChiKey: RQRTWBCHAVTWIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.75
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  42.22
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-(tert-butyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium on carbon 、 氢气 、 caesium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-amino-1-(3-(3,5-difluorophenylamino)-2-(4-fluorophenyl)-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)-2-methylpropan-1-one
  参考文献：
  名称：

  Imidazolopiperazines: Hit to Lead Optimization of New Antimalarial Agents

  摘要：

  Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. The lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. In a Plasmodium berghei mouse infection model, one lead compound lowered the parasitemia level by 99.4% after administration of 100 mg/kg single oral dose and prolonged mice survival by an average of 17.0 days. The lead compounds were also well-tolerated in the preliminary in vitro toxicity studies and represents an interesting lead for drug development.

  DOI：

  10.1021/jm2003359
• 作为产物：
  描述：

  氨基吡嗪 、 异氰酸叔丁酯 、 对氟苯甲醛 在 calcium(II) trifluoromethanesulfonate 作用下， 以 neat (no solvent) 为溶剂， 反应 0.08h， 以87%的产率得到N-(tert-butyl)-2-(4-fluorophenyl)imidazo[1,2-a]pyrazin-3-amine
  参考文献：
  名称：

  Design, synthesis and anticancer activity of 2-arylimidazo[1,2-a]pyridinyl-3-amines

  摘要：

  A series of imido-heterocycle compounds were designed, synthesized, characterized, and evaluated for the anticancer potential using breast (MCF-7 and MDA-MB-231), pancreatic (PANC-1), and colon (HCT-116 and HT-29) cancer cell lines and normal cells, while normal cells showed no toxicity. Among the screened compounds, 4h exhibited the best anticancer potential with IC50 values ranging from 1 to 5.5 μM. Compound 4h caused G2/M phase arrest and apoptosis in all the cell lines except MDA-MB-231 mammosphere formation was inhibited. In-vitro enzyme assay showed selective topoisomerase IIα inhibition by compound 4h, leading to DNA damage as observed by fluorescent staining. Cell signalling studies showed decreased expression of cell cycle promoting related proteins while apoptotic proteins were upregulated. Interestingly MDA-MB-231 cells showed only cytostatic effects upon treatment with compound 4h due to defective p53 status. Toxicity study using overexpression of dominant-negative mutant p53 in MCF-7 cells (which have wild type functional p53) showed that anticancer potential of compound 4h is positively correlated with p53 expression.

  DOI：

  10.1016/j.bioorg.2021.105464