Design and synthesis of indane-ureido-thioisobutyric acids: A novel class of PPARα agonists

The synthesis and SAR of novel, highly potent PPARα agonists based on an indane scaffold are reported. A series of aminoindane derivatives were synthesized and shown to be potent PPARα agonists. The compounds were obtained as racemates in 12 steps, and tested for PPARα activation and PPARα mediated induction of the HD gene. SAR was developed by variation to the core structure as shown within. Oral bioavailability was demonstrated in a Sprague–Dawley rat, while efficacy to reduce plasma triglycerides and plasma glucose was demonstrated in db/ db mice.