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

To develop novel PPARgamma 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 PPARgamma protein where the alkyl chain of 15d-PGJ2 is expected to be located.