Design, synthesis and structure-activity relationship studies of human dihydroorotate dehydrogenase inhibitors / 药学学报
Acta Pharmaceutica Sinica
; (12): 264-270, 2017.
Article
in Chinese
| WPRIM (Western Pacific)
| ID: wpr-779588
Responsible library:
WPRO
ABSTRACT
In this study, 1-(3-(4-chlorophenyl)-5-methylthio-1H-1,2,4-triazol-1-yl)-butan-1-one discovered previously in our lab was selected as a inhibitor of human dihydroorotate dehydrogenase (HsDHODH) for structural optimization. The co-crystal of HsDHODH with the hit was obtained and analyzed for guiding the subsequent structural optimization. As a result, a series of novel triazole derivatives were designed and synthesized as potent HsDHODH inhibitors. Among them, compound (3-(4-chlorophenyl)-5-ethylthio-1H-1,2,4-triazol-1-yl)-furan-2-yl-methanone displayed high potency in the inhibition of HsDHODH with an IC50 value of 1.50 μmol·L-1. Meanwhile, the structure-activity relationships were analyzed based on the biological data and the co-crystal structure. These results provide a valuable reference for optimization of 1H-1,2,4-triazole derivatives as HsDHODH inhibitors in the future.
Full text:
Available
Database:
WPRIM (Western Pacific)
Language:
Chinese
Journal:
Acta Pharmaceutica Sinica
Year:
2017
Document type:
Article