Abstract
Design, synthesis, and SAR of novel alpha-alkoxy-beta-arylpropionic acids as potent and balanced PPARalphagamma coagonists are described. One representative thereof, Aleglitazar ((S)-2Aa), was chosen for clinical development. Its X-ray structure in complex with both receptors as well as its high efficacy in animal models of T2D and dyslipidemia are also presented.
MeSH terms
-
Animals
-
Chemistry, Pharmaceutical / methods
-
Crystallography, X-Ray / methods
-
Diabetes Mellitus, Type 2 / drug therapy*
-
Drug Design
-
Dyslipidemias / drug therapy
-
Humans
-
Inhibitory Concentration 50
-
Ligands
-
Models, Chemical
-
Molecular Structure
-
Oxazoles / chemical synthesis*
-
Oxazoles / pharmacology*
-
PPAR alpha / agonists*
-
PPAR gamma / agonists*
-
Receptors, Cytoplasmic and Nuclear / metabolism
-
Thiophenes / chemical synthesis*
-
Thiophenes / pharmacology*
Substances
-
Ligands
-
Oxazoles
-
PPAR alpha
-
PPAR gamma
-
Receptors, Cytoplasmic and Nuclear
-
Thiophenes
-
aleglitazar