Sierra, Michael L. published the artcileSubstituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents, Application In Synthesis of 144060-99-1, the main research area is arylmethylpropionic acid derivative SAR preparation PPAR agonist HDLc raising.
The peroxisome proliferator activated receptors PPARα, PPARγ, and PPARδ are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-d. lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPARα agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPARα agonists. Modification of the selective PPARδ agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPARα agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPARα and at least 500-fold selectivity vs. PPARδ and PPARγ. Compound 25a (GW590735) has been progressed to clin. trials for the treatment of diseases of lipid imbalance.
Journal of Medicinal Chemistry published new progress about Lipid metabolism disorders Role: BIOL (Biological Study). 144060-99-1 belongs to class thiazole, name is 2-(4-Fluorophenyl)-4-methylthiazole-5-carboxylic acid, and the molecular formula is C11H8FNO2S, Application In Synthesis of 144060-99-1.
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica