Design, synthesis and biological evaluation of N-phenylthieno[2,3-d]pyrimidin-4-amines as inhibitors of FGFR1

Fibroblast grow factor receptor 1 (FGFR1) is an important anti-cancer target that plays crucial role in oncogenesis and oncogenic angiogenesis. The structure–activity relationship (SAR) of N-phenylthieno[2,3-d]pyrimidin-4-amines was investigated. Binding of active compounds with FGFR1 kinase was analyzed by molecular modeling studies. Selected active thieno[2,3-d]pyrimidines were tested for selectivity and antiproliferative activity. The most active compounds, 3-({6-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol and 3-({5-phenylthieno[2,3-d]pyrimidin-4-yl}amino)phenol have IC50 0.16 and 0.18 μM, respectively. The results presented here may help to identify new thienopyrimidines with optimized cell growth inhibitory activity which may be further used as anticancer agents.

Protein kinase FGFR1 inhibitors: We report a series of N-phenylthieno[2,3-d]pyrimidin-4-amines as a novel class of nanomolar-range FGFR1 inhibitors. These new FGFR1 inhibitors showed a good selectivity and antiproliferative activity on cancer cell line.Figure optionsDownload as PowerPoint slide