Synthesis of new carbo- and heterocyclic analogues of 8-HETE and evaluation of their activity towards the PPARs.
A new class of dual PPARs alpha and gamma 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 alpha and gamma 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.
Caijo
Frédéric
F
ENSCR, Laboratoire de Synthèse et Activation de Biomolécules, CNRS UMR 6052, Avenue du Général Leclerc, 35700 Rennes-Beaulieu, France.
Mosset
Paul
P
Grée
René
R
Audinot-Bouchez
Valérie
V
Boutin
Jean
J
Renard
Pierre
P
Caignard
Daniel-Henri
DH
Dacquet
Catherine
C
D000818:Animals; D019556:COS Cells; D004353:Drug Evaluation, Preclinical; D006893:Hydroxyeicosatetraenoic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*
D006893:Hydroxyeicosatetraenoic Acids; D047493:PPAR alpha; D047495:PPAR gamma; C047628:8-hydroxyeicosatetraenoic acid