Design and Synthesis of Novel 1,3-Dioxane-2-carboxylic Acid Derivatives as PPARα/γ Dual Agonists

Title: Design and Synthesis of Novel 1,3-Dioxane-2-carboxylic Acid Derivatives as PPARα/γ Dual Agonists

Volume: 7 Issue: 6

Author(s): Harikishore Pingali, Mukul Jain, Shailesh Shah, Pankaj Makadia, Pandurang Zaware, Jeevankumar Jamili, Kalapatapu V.V.M. Sairam, Pravin Patil, Dinesh Suthar, Suresh Giri, Harilal Patel and Pankaj Patel

Affiliation:

Keywords: PPAR agonist, PPAR α/γ dual agonists, Type 2 diabetes, 1,3-dioxane carboxylic acid

Abstract: 1,3-dioxane carboxylic acid derivatives were prepared based on our previous studies directed towards identifying novel pharmacophore for the development of PPAR α/γ dual agonists. Based on the typical topology of PPAR agonists we focused our design approach on modifying lipophilic tail and prepared a series of compounds by replacing the oxazole moiety of our previously reported compound with optimized lipophilic groups. Compound 8a was found to be a weak PPAR activator but exhibited potent hypolipidemic and anti-hyperglycemic activities in vivo due to superior bioavailability, whereas 8f exhibited potent in vitro and invivo effects. The activity of 8f is further supported by molecular docking study.

Cite this article as:

Pingali Harikishore, Jain Mukul, Shah Shailesh, Makadia Pankaj, Zaware Pandurang, Jamili Jeevankumar, V.V.M. Sairam Kalapatapu, Patil Pravin, Suthar Dinesh, Giri Suresh, Patel Harilal and Patel Pankaj, Design and Synthesis of Novel 1,3-Dioxane-2-carboxylic Acid Derivatives as PPARα/γ Dual Agonists, Letters in Drug Design & Discovery 2010; 7 (6) . https://dx.doi.org/10.2174/157018010791306533

DOI https://dx.doi.org/10.2174/157018010791306533	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X