4,4-Dimethyl-1,2,3,4-tetrahydroquinoline-based PPARα/γ agonists. Part I: Synthesis and pharmacological evaluation

Type-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic β-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARα, PPARγ and PPARβ/(δ). 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 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as novel cyclic tail.

Graphical abstractType-2 diabetes (T2D) is a complex metabolic disease characterized by insulin resistance in the liver and peripheral tissues accompanied by a defect in pancreatic β-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARα, PPARγ and PPARβ/(δ). In this course, 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 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as novel cyclic tail.Figure optionsDownload full-size imageDownload as PowerPoint slide