Synthesis and biological evaluation of substituted indazolyl amide derivatives as S-adenosyl-l-homocysteine hydrolase inhibitors

A series of novel amide derivatives bearing an indazole moiety were synthesized and evaluated for their in vitro S-adenosyl-l-homocysteine hydrolase (SAHase) inhibitory activity. Among these compounds, 8b, 8m, 8r and 8w showed better or similar inhibitory effects compared to the positive control aristeromycin. These results provide a novel lead for the discovery of more potent non-adenosine analogs as SAHase inhibitors.

Graphical abstractA series of novel amide derivatives containing an indazole moiety were synthesized, and compound 8w exhibited the most potent SAHase inhibitory activity with an IC50 value of 0.44 μmol/L.Figure optionsDownload full-size imageDownload as PowerPoint slide