328918-85-0Relevant academic research and scientific papers
Aleglitazar, a new, potent, and balanced dual PPARα/γ agonist for the treatment of type II diabetes
Benardeau, Agnes,Benz, Joerg,Binggeli, Alfred,Blum, Denise,Boehringer, Markus,Grether, Uwe,Hilpert, Hans,Kuhn, Bernd,Maerki, Hans Peter,Meyer, Markus,Puentener, Kurt,Raab, Susanne,Ruf, Armin,Schlatter, Daniel,Mohr, Peter
scheme or table, p. 2468 - 2473 (2010/03/24)
Design, synthesis, and SAR of novel α-alkoxy-β-arylpropionic acids as potent and balanced PPARαγ 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.
Synthesis and evaluation of aminomethyl dihydrocinnamates as a new class of PPAR ligands
Warshawsky, Alan M.,Alt, Charles A.,Brozinick, Joseph T.,Harkness, Allen R.,Hawkins, Eric D.,Henry, James R.,Matthews, Donald P.,Miller, Anne R.,Misener, Elizabeth A.,Montrose-Rafizadeh, Chahrzad,Rhodes, Gary A.,Shen, Quanrong,Vance, Jennifer A.,Udodong, Uko E.,Wang, Minmin,Zhang, Tony Y.,Zink, Richard W.
, p. 6328 - 6333 (2007/10/03)
PPAR ligands with varied subtype selectivity have been synthesized using an achiral aminomethyl dihydrocinnamate template. Several compounds in this series have demonstrated potent plasma glucose and triglyceride lowering capability in rodent models of type 2 diabetes.
HETEROCYCLIC COMPOUNDS AS MODULATORS OF PEROXISOME PROLIFERATOR ACTIVATED RECEPTORS, USEFUL FOR THE TREATMENT AND/OR PREVENTION OF DISORDERS MODULATED BY A PPAR
-
Page/Page column 55, (2010/02/11)
The present invention is directed to a compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate or stereoisomer thereof, which is useful in treating or preventing disorders mediated by a peroxisome proliferator activated receptor (PPAR) such as syndrome X, type II diabetes, hyperglycemia, hyperlipidemia, obesity, coagaulopathy, hypertension, arteriosclerosis, and other disorders related to syndrome X and cardiovascular diseases.
Conversion of human-selective PPARα agonists to human/mouse dual agonists: A molecular modeling analysis
Wang, Minmin,Winneroski, Leonard L.,Ardecky, Robert J.,Babine, Robert E.,Brooks, Dawn A.,Etgen, Garret J.,Hutchison, Darrell R.,Kauffman, Raymond F.,Kunkel, Aaron,Mais, Dale E.,Montrose-Rafizadeh, Chahrzad,Ogilvie, Kathleen M.,Oldham, Brian A.,Peters, Mary K.,Rito, Christopher J.,Rungta, Deepa K.,Tripp, Allie E.,Wilson, Sarah B.,Xu, Yanping,Zink, Richard W.,McCarthy, James R.
, p. 6113 - 6116 (2007/10/03)
To understand the species selectivity in a series of α-methyl- α-phenoxy carboxylic acid PPARα/γ dual agonists (1-11), structure-based molecular modeling was carried out in the ligand binding pockets of both human and mouse PPARα. This study suggested that interaction of both 4-phenoxy and phenyloxazole substituents of these ligands with F272 and M279 in mouse PPARα leads to the species-specific divergence in ligand binding. Insights obtained in the molecular modeling studies of these key interactions resulted in the ability to convert a human-selective PPARα agonist to a human and mouse dual agonist within the same platform.
Design and synthesis of 2-methyl-2-{4-[2-(5-methyl-2-aryloxazol-4-yl)ethoxy]phenoxy}propionic acids: A new class of dual PPARα/γ agonists
Brooks,Etgen,Rito,Shuker,Dominianni,Warshawsky,Ardecky,Paterniti,Tyhonas,Karanewsky,Kauffman,Broderick,Oldham,Montrose-Rafizadeh,Winneroski,Faul,McCarthy
, p. 2061 - 2064 (2007/10/03)
Propionic acid derivative 8, which was designed and synthesized based on putative pharmacophores of known PPARγ- and PPARα-selective compounds, exhibits potent dual PPARα/γ agonist activity as demonstrated by in vitro binding and dose overlap in the newly
