Design, synthesis, and activity of 5-cyano-2-thiacetyl aromatic pyrimidinone as DENV NS5 RdRp inhibitors / 药学学报
Acta Pharmaceutica Sinica
; (12): 3379-3388, 2023.
Article
Dans Zh
| WPRIM
| ID: wpr-999072
Responsable en Bibliothèque :
WPRO
ABSTRACT
To screen novel anti-dengue virus (DENV) NS5 RdRp enzyme inhibitors, a series of 5-cyano-2-thiacetoaryl pyrimidinone compounds were designed and synthesized by molecular hybridization method with HCV NS5B RdRp inhibitor 3jc and ZIKV NS5 RdRp inhibitor 4w as lead compounds. The anti-DENV activity of these compounds was evaluated by MTT assay and plaque assay and five compounds showed anti-DENV activity. The most active compound 7a'k showed better anti-DENV activity than that of the positive control ribavirin (EC50 = 7.86 μmol·L-1 vs EC50 = 18.07 μmol·L-1), and the other four compounds showed almost the same anti-DENV activity as ribavirin. Finally, the prediction and simulation of the binding mode through molecular provided new ideas for the further development of this new DENV NS5 RdRp inhibitor.
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WPRIM
langue:
Zh
Texte intégral:
Acta Pharmaceutica Sinica
Année:
2023
Type:
Article