Design, synthesis, and biological activity of novel PPARγ ligands based on rosiglitazone and 15d-PGJ2

Article abstract of DOI:10.1016/j.bmcl.2005.01.074

To develop novel PPARγ ligands, we synthesized thirteen 3-{4-(2-aminoethoxy)phenyl}propanoic acid derivatives, which are designed based on the structures of rosiglitazone and 15d-PGJ₂. Among these compounds, compound 9 was found to be as potent as rosiglitazone in a binding assay and a preadipocyte differentiation test. Molecular modeling suggested that the nonyl group of 9 interacted with hydrophobic amino acid residues constructing the hydrophobic region of PPARγ protein where the alkyl chain of 15d-PGJ₂ is expected to be located.