401468-50-6Relevant academic research and scientific papers
PYRIMIDINYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
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Page/Page column 14, (2010/10/03)
The present invention disclosed compounds of Structural Formula (I), and enantiomer, racemic body, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein variable groups are as defined within, as well as methods for preparing such compou
PYRIMIDINYL-PROPIONIC ACID DERIVATIVES AND THEIR USE AS PPAR AGONISTS
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Page/Page column 19-20, (2009/05/30)
The present invention disclosed compounds of Structural Formula (I), and enantiomer, racemic body, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein variable groups are as defined within, as well as methods for preparing such compou
Discovery of novel dual functional agent as PPARγ agonist and 11β-HSD1 inhibitor for the treatment of diabetes
Ye, Yang-liang,Zhou, Zhou,Zou, Han-jun,Shen, Yu,Xu, Ti-fei,Tang, Jing,Yin, Hua-zhong,Chen, Min-li,Leng, Ying,Shen, Jian-hua
scheme or table, p. 5722 - 5732 (2009/12/28)
PPARγ and 11β-HSD1 are attractive therapeutic targets for type 2 diabetes. However, PPARγ agonists induce adipogenesis, which causes the side effect of weight gain, whereas 11β-HSD1 inhibitors prevent adipogenesis and may be beneficial for the treatment of obesity in diabetic patients. For the first time, we designed, synthesized a series of α-aryloxy-α-methylhydrocinnamic acids as dual functional agents which activate PPARγ and inhibit 11β-HSD1 simultaneously. The compound 11e exhibited the most potent inhibitory activity compared to that of the lead compound 2, with PPARγ (EC50 = 6.76 μM) and 11β-HSD1 (IC50 = 0.76 μM) in vitro. Molecular modeling study for compound 11e was also presented. Compound 11e showed excellent efficacy for lowering glucose, triglycerides, body fat, in well established mice and rats models of diabetes and obesity and had a favorable ADME profile.
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 α-Aryloxy-α-methylhydrocinnamic Acids: A Novel Class of Dual Peroxisome Proliferator-Activated Receptor α/ γ Agonists
Xu, Yanping,Rito, Christopher J.,Etgen, Garret J.,Ardecky, Robert J.,Bean, James S.,Bensch, William R.,Bosley, Jacob R.,Broderick, Carol L.,Brooks, Dawn A.,Dominianni, Samuel J.,Hahn, Patric J.,Liu, Sha,Mais, Dale E.,Montrose-Rafizadeh, Chahrzad,Ogilvie, Kathy M.,Oldham, Brian A.,Peters, Mary,Rungta, Deepa K.,Shuker, Anthony J.,Stephenson, Gregory A.,Tripp, Allie E.,Wilson, Sarah B.,Winneroski, Leonard L.,Zink, Richard,Kauffman, Raymond F.,McCarthy, James R.
, p. 2422 - 2425 (2007/10/03)
The design and synthesis of the dual peroxisome proliferator activated receptor (PPAR) α/γ agonist (S)-2-methyl-3-{4-[2-(5-methyl-2-thiophen-2-yl-oxazol-4-yl)ethoxy]phenyl} -2-phenoxypropionic acid (2) for the treatment of type 2 diabetes and associated d
