4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARα/γ agonists. Part. II: Synthesis and pharmacological evaluation of oxime and acidic head group structural variations

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 β-cells. Since their discovery, three subtypes of peroxisome proliferator activated receptors have been identified, namely PPARα, PPARγ and PPARβ/(δ). In this study, we were interested in designing novel PPARγ selective agonists and/or dual PPARα/γ 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.