Letters in Drug Design & Discovery

G. Perry
University of Texas
San Antonio, TX
USA
Email: lddd@benthamscience.org

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

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, Pankaj Patel.

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.

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

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Article Details

VOLUME: 7
ISSUE: 6
Year: 2010
Page: [421 - 429]
Pages: 9
DOI: 10.2174/157018010791306533
Price: $58