Parmenon Cécile, Guillard Jérôme, Caignard Daniel-Henri, Hennuyer Nathalie, Staels Bart, Audinot-Bouchez Valérie, Boutin Jean-Albert, Dacquet Catherine, Ktorza Alain, Viaud-Massuard Marie-Claude
SPOT-EA3857, UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France.
Bioorg Med Chem Lett. 2008 Mar 1;18(5):1617-22. doi: 10.1016/j.bmcl.2008.01.067. Epub 2008 Jan 19.
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 beta-cell. Since their discovery three subtypes of Peroxisomes Proliferators Activated Receptors were identified namely PPARalpha, PPARgamma and PPARbeta/(delta). 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 4,4-dimethyl-1,2,3,4-tetrahydroquinoline as novel cyclic tail.
2型糖尿病（T2D）是一种复杂的代谢性疾病，其特征是肝脏和外周组织存在胰岛素抵抗，并伴有胰腺β细胞功能缺陷。自过氧化物酶体增殖物激活受体被发现以来，已鉴定出三种亚型，即PPARα、PPARγ和PPARβ/（δ）。我们对设计新型PPARγ选择性激动剂和/或PPARα/γ双重激动剂感兴趣。基于合成PPAR激动剂的典型拓扑结构，我们将设计方法聚焦于4,4-二甲基-1,2,3,4-四氢喹啉作为新型环状尾端。
