2. Academic Validation
  3. Design and synthesis of indane-ureido-thioisobutyric acids: A novel class of PPARalpha agonists

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

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6773-8. doi: 10.1016/j.bmcl.2007.10.041.
Jay M Matthews 1,  Xiaoli Chen,  Ellen Cryan,  Dennis J Hlasta,  Philip J Rybczynski,  Kim Strauss,  Yuting Tang,  June Z Xu,  Maria Yang,  Lubing Zhou,  Keith T Demarest
Affiliations

Affiliation

  • 1 Drug Discovery, Johnson & Johnson, East Coast RED, Spring House, PA 19477-0776, USA. jmatthew@prdus.jnj.com
PMID: 18029176 DOI: 10.1016/j.bmcl.2007.10.041
Abstract

A series of aminoindane derivatives were synthesized and shown to be potent PPARalpha agonists. The compounds were obtained as racemates in 12 steps, and tested for PPARalpha activation and PPARalpha 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.

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