Design, synthesis, and PPARα/γ agonistic activity of novel tetrahydroisoquinoline derivatives

A series of tetrahydroisoquinoline derivatives were prepared and their peroxisome proliferator- activated receptor (PPAR) α/γ agonistic activities were evaluated to obtain more potent PPAR agonist.  All of them were new compounds, and their structures were confirmed by ¹H NMR and HR-MS.  Three compounds exhibited higher agonistic activities of PPARγ than that of the comparison, six compounds exhibited higher agonistic activities of PPARα than that of the comparison, and compound 8a was discovered as a highly potent PPARα/γ agonist that is much more active than that of WY14643 and rosiglitazone.  The development of potent PPAR agonists may offer a new choice for the treatment of diabetes.