439134-88-0Relevant academic research and scientific papers
Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARα agonists. 1. Discovery of a novel series of potent HDLc raising agents
Sierra, Michael L.,Beneton, Véronique,Boullay, Anne-Bénédict,Boyer, Thierry,Brewster, Andrew G.,Donche, Frédéric,Forest, Marie-Claire,Fouchet, Marie-Hélène,Gellibert, Fran?oise J.,Grillot, Didier A.,Lambert, Millard H.,Laroze, Alain,Le Grumelec, Christelle,Linget, Jean Michel,Montana, Valerie G.,Nguyen, Van-Loc,Nicodème, Edwige,Patel, Vipul,Penfornis, Annie,Pineau, Olivier,Pohin, Danig,Potvain, Florent,Poulain, Géraldine,Ruault, Cécile Bertho,Saunders, Michael,Toum, Jér?me,Xu, H. Eric,Xu, Robert X.,Pianetti, Pascal M.
, p. 685 - 695 (2007/10/03)
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-density 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 versus PPARγ and PPARγ. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.
COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS
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Page/Page column 25, (2010/02/14)
The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPAR.
CHEMICAL COMPOUNDS
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, (2010/02/05)
A compound of formula (I) or a pharmaceutically acceptable salt, solvate, or hydrolysable ester thereof, .Wherein:R1 and R2 are independently hydrogen or C1-3 alkyl;X represents a bond, CH2 or O;R3 and R4 are independently hydrogen, C1-6 alkyl, OCH3, CF3, allyl or halogen;X1 is CH2, SO2, or CO;R5 is -C1-6 alkyl (optionally substituted by C1-6alkoxy or C1-6alkylthio), -C2-6 alkenyl, -C0-6 alkyl phenyl (wherein the phenyl is optionally substituted by one or more CF3, halogen, C1-3 alkyl, C1-3 alkoxy), -COC1-6 alkyl, SO2C1-6 alkyl ;R6 is phenyl or a 6 membered heteroaryl group containing 1,2 or 3 N atoms wherein the phenyl or heteroaryl group is optionally substituted with 1, 2 or 3 moieties selected from the group consisting of C1-6 alkyl, halogen, -OC1-6 alkyl, -SO2C1-3 alkyl, phenyl (optionally substituted by one or more groups selected from halogen, CF3, C1-3 alkyl, OC1-3 alkyl, acetyl, CN).
