Synthesis and pharmacological evaluation of novel benzoylazole-based PPAR α/γ activators

  • Bioorg Med Chem Lett. 2011 Apr 1;21(7):1978-82. doi: 10.1016/j.bmcl.2011.02.032.
Kantaro Ushiroda  1 ,  Katsunori Maruta ,  Takeshi Takazawa ,  Tomokazu Nagano ,  Mutsuo Taiji ,  Tetsuya Kohno ,  Yasuhiro Sato ,  Shinji Horai ,  Kazunori Yanagi ,  Ryu Nagata
Affiliations
  • 1. Dainippon Sumitomo Pharma Co, Ltd, Drug Research Division, Chemistry Research Laboratories, Osaka, Japan. [email protected]
PMID: 21377875 DOI: 10.1016/j.bmcl.2011.02.032
Abstract

In our search for new PPARα/γ agonists, we designed and synthesized a series of benzoylazole-based carboxylic acids. Compound 9 showed potent PPARγ partial agonistic activity with modest PPARα agonistic activity. The sodium salt of 9 (9Na) demonstrated potent efficacy in lowering both blood glucose and lipids in an animal model without causing significant body weight gain, a well-known side effect associated with PPARγ full agonists.