DESIGN,SYNTHESIS, AND EVALUATION OFTETRAHYDROQUINOLINE-LINKED THIAZOLIDINEDIONEDERIVATIVES AS PPARy SELECTIVE ACTIVATORS

摘要

A series of tetrahydroquinoline-linked thiazolidinediones was designed and synthesized and their peroxisome proliferator activated receptor-gamma (PPARgamma) agonistic activities were evaluated. A number of analogs were revealed to have significant PPARy agonistic activity. Among these compounds, compound lh possessing N-heptyl moiety was found to be the most active in PPARgamma transactivation assay. Molecular modeling suggested that the heptyl group of lh appropriately interacts with hydrophobic amino acid residues in the active site of PPARgamma.