Design,synthesis and biological evaluation of phenylsulfonamide-based IDO1 inhibitors / 中国药科大学学报

Based on the reported IDO1 inhibitor U-3i,11 phenylsulfonamide derivatives were designed and syn-thesized by adopting bioisosterism and molecular docking technology.The inhibitory activities of the target compounds against IDO1 were determined by the HeLa cell-based kynurenine assay.The results demonstrated that most compounds showed different degrees of inhibitory effects on IDO1.Among them,compounds 3b and 3e displayed the most potent activity and could reverse IDO1-mediated immune suppression,which might be worth of further investigation.

Design, synthesis and biological evaluation of pyridine-based IRAK4 inhibitors / 中国药科大学学报

Based on the known IRAK4 inhibitors MK-32 and AU-5,we designed and synthesized 12 pyridine-based target compounds by adopting open-ring and hybrid strategies,and combining molecular docking technology.The bioassays determined by radioisotope labeling demonstrated that the target compounds displayed good inhibitory activity against IRAK4.Among them,the IC50 value of 5 compounds was less than 1 μmol/L,suggesting that these compounds may be candidates for further investigation.