Synthesis and JAK2 inhibitory activities of 4-phenyl-pyrrolo[2, 3-d] pyrimidine derivatives / 中国药科大学学报
Journal of China Pharmaceutical University
; (6): 150-156, 2017.
Artigo
em Chinês
| WPRIM (Pacífico Ocidental)
| ID: wpr-613410
Biblioteca responsável:
WPRO
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,SNAr reaction,cyclized,dehydration,Suzuki coupling and finally acylated to give 12 new compounds(12a-121).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 tide compounds exhibited potent antiproliferative effect on A549,especially compound 12c(IC50 =0.12 μmol/L),suggesting that this series compounds might be promising anti-tumor agents for futher investigation.
Texto completo:
Disponível
Base de dados:
WPRIM (Pacífico Ocidental)
Idioma:
Chinês
Revista:
Journal of China Pharmaceutical University
Ano de publicação:
2017
Tipo de documento:
Artigo