Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenaseThe authors declare no competing interests.Electronic supplementary information (ESI) available. See DOI: 10.1039/c7md00081b

A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase ( h DHODH) inhibitors. Compounds 26 and 31 displayed IC 50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound 31 could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with Ala55, which may be necessary for maintaining the bioactivities of the compounds in this series. Further structural optimization of the para - or meta -position of the phenyl group at R will lead to the identification of more potent h DHODH inhibitors. A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase ( h DHODH) inhibitors.