Design and synthesis of novel oxazole containing 1,3-dioxane-2-carboxylic acid derivatives as PPAR alpha/gamma dual agonists

  • Bioorg Med Chem. 2008 Aug 1;16(15):7117-27. doi: 10.1016/j.bmc.2008.06.050.
Harikishore Pingali  1 ,  Mukul Jain ,  Shailesh Shah ,  Pankaj Makadia ,  Pandurang Zaware ,  Ashish Goel ,  Megha Patel ,  Suresh Giri ,  Harilal Patel ,  Pankaj Patel
Affiliations
  • 1. Zydus Research Centre, Sarkhej-Bavla N.H 8A Moraiya, Ahmedabad 382210, India. [email protected]
PMID: 18625559 DOI: 10.1016/j.bmc.2008.06.050
Abstract

A few novel 1,3-dioxane carboxylic acid derivatives were designed and synthesized to aid in the characterization of PPAR alpha/gamma dual agonists. Structural requirements for PPARalpha/gamma dual agonism of 1,3-dioxane carboxylic acid derivatives included the structural similarity with potent glitazones in fibric acid chemotype. The compounds with this pharmacophore and substituted oxazole as a lipophilic heterocyclic tail were synthesized and evaluated for their in vitro PPAR agonistic potential and in vivo hypoglycemic and hypolipidemic efficacy in animal models. Lead compound 2-methyl-c-5-[4-(5-methyl-2-(4-methylphenyl)-oxazol-4-ylmethoxy)-benzyl]-1,3-dioxane-r-2-carboxylic acid 13b exhibited potent hypoglycemic, hypolipidemic and Insulin sensitizing effects in db/db mice and Zucker fa/fa rats.