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  • Title: 4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARalpha/gamma agonists. Part. II: Synthesis and pharmacological evaluation of oxime and acidic head group structural variations.
    Author: Parmenon C, Guillard J, Caignard DH, Hennuyer N, Staels B, Audinot-Bouchez V, Boutin JA, Dacquet C, Ktorza A, Viaud-Massuard MC.
    Journal: Bioorg Med Chem Lett; 2009 May 15; 19(10):2683-7. PubMed ID: 19376700.
    Abstract:
    Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a deficiency in pancreatic beta-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARalpha, PPARgamma and PPARbeta/(delta). In this study, we were interested in designing novel PPARgamma selective agonists and/or dual PPARalpha/gamma agonists. Based on the typical topology of synthetic PPAR agonists, we focused our design approach on using 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as a novel cyclic scaffold with oxime and acidic head group structural variations.
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