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.     

Synthesis and biological evaluation of novel SIPI-7623 derivatives as farnesoid X receptor (FXR) antagonists

Most of reported steroidal FXR antagonists are restricted due to low potency. We described the design and synthesis of novel nonsteroidal scaffold SIPI-7623 derivatives as FXR antagonists. The most potent compound A-11 (IC₅₀?=?7.8?±?1.1 μM) showed better activity compared to SIPI-7623 (IC₅₀?=?40.8?±?1.7 μM) and guggulsterone (IC₅₀?=?45.9?±?1.1 μM). Docking of A-11 in FXR’s ligand-binding domain was also studied.