Design and synthesis of novel oxazole containing 1,3-dioxane-2-carboxylic acid derivatives as PPAR alpha/gamma dual agonists |
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Authors: | Pingali Harikishore Jain Mukul Shah Shailesh Makadia Pankaj Zaware Pandurang Goel Ashish Patel Megha Giri Suresh Patel Harilal Patel Pankaj |
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Institution: | Zydus Research Centre, Sarkhej-Bavla N.H 8A Moraiya, Ahmedabad 382210, India. pingalihk@rediffmail.com |
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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. |
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