Research of the past years has provided clear evidence that PPARβ/δ is associated with major diseases including cancer, atherosclerosis and diabetes mellitus. Modulation of this receptor by specific inhibitory ligands represents a potential therapeutic option. At the beginning of this work highly affine agonists for PPARβ/δ were available, but all described inhibitory ligands were either not selective, not bioavailable or showed a pharmacologically undesirable, irreversible interaction with PPARβ/δ. To investigate the therapeutic potential of PPARβ/δ ligands the development of new was highly desirable. These include antagonists, which inhibit PPARβ/δ activity by competition with endogenous ligands, and inverse agonists, which actively trigger corepressor recruitment and establishment of an active transcriptional repressor complex.
