Abstract:
A series of 4-phenyl-pyrrolo[2, 3-d]pyrimidine derivatives were synthesized through modifying the structure of the lead compound ruxolitinib by molecular hybridization strategy. It was synthesized from pyrimidine-4, 6-diol by Vilsmeier-Haack reaction, S
NAr reaction, cyclized, dehydration, Suzuki coupling and finally acylated to give 12 new compounds(
12a -
12l ). All structures of the synthesized compounds were confirmed by
1H NMR,
13C NMR, and HRMS analysis. The biological activities were evaluated
in vitro. Their JAK2 inhibitory activities were studied using JAK2 enzymatic and TF1-GMCSF cellular assays. The results indicated that compounds
12b ,
12e and
12h showed moderate activity. The anti-tumor activities were studied against JAK2-independent A549 cell line by the MTT assay. Results showed that the title compounds exhibited potent antiproliferative effect on A549, especially compound
12c (IC
50=0. 12 μmol/L), suggesting that this series compounds might be promising anti-tumor agents for futher investigation.