Synthesis of new carbo- and heterocyclic analogues of 8-HETE and evaluation of their activity towards the PPARs

A new class of dual PPARs α and γ agonists was developed. These compounds are structural analogues of the arachidonic acid metabolite, the 8-(S)-HETE. A versatile strategy has been introduced to prepare the target molecules having different carbo- and heterocyclic cores and to modulate the unsaturations on the side chains. Their affinity towards the PPARs α and γ receptors is reported, together with their transactivation percentage. Most of these derivatives have a good activity as dual agonists but the quinoline-derived products appear as the most promising compounds.

Graphical abstractA new class of dual PPARs α and γ agonists has been developed. Most of these derivatives have a good activity but the quinoline-derived products appear as the most promising compounds.Figure optionsDownload full-size imageDownload as PowerPoint slide