5-aryl thiazolidine-2,4-diones: discovery of PPAR dual alpha/gamma agonists as antidiabetic agents

  • Bioorg Med Chem Lett. 2003 Aug 18;13(16):2795-8. doi: 10.1016/s0960-894x(03)00505-5.
Ranjit C Desai  1 ,  Wei Han ,  Edward J Metzger ,  Jeffrey P Bergman ,  Dominick F Gratale ,  Karen L MacNaul ,  Joel P Berger ,  Thomas W Doebber ,  Kwan Leung ,  David E Moller ,  James V Heck ,  Soumya P Sahoo
Affiliations
  • 1. Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. [email protected]
PMID: 12873517 DOI: 10.1016/s0960-894x(03)00505-5
Abstract

A novel series of 5-aryl thiazolidine-2,4-diones based dual PPARalpha/gamma agonists was identified. A number of highly potent and orally bioavailable analogues were synthesized. Efficacy study results of some of these analogues in the db/db mice model of type 2 diabetes showed them superior to rosiglitazone in correcting hyperglycemia and hypertriglyceridemia.