175136-29-5Relevant academic research and scientific papers
Oxazolyl-aryloxyacetic acid derivatives and their use as ppar agonists
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, (2008/06/13)
Compounds represented by the following (I), and pharmaceutically acceptable salts, solvates and hydrates thereof, wherein R1 is an unsubstituted or substituted aryl, heteroaryl, cycloalkyl, aryl-alkyl, heteroaryl-alkyl or cycloalkyl-alkyl, R2 is H, alkyl or haloalkyl, the polymethylene chain (II), is saturated or may contain a carbon-carbon double bond, while n is 2, 3, 4, W is O or S, Y is an unsubsituted or substituted phenylene, naphthylene or 1, 2, 3, 4 tetrahydronaphthylene, R3 is H, alkyl or haloalkyl. R4 is H, alkyl, haloalkyl or a substituted or unsubstituted benzyl, are useful for modulating a peroxisome proliferator activated receptor, particularly in the treatment of diabetes mellitus.
1,2-disubstituted-6-oxo-3-phenyl-piperidine-3-carboxamides and combinatorial libraries thereof
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, (2008/06/13)
The invention relates to combinatorial libraries containing two or more novel piperidine-3-carboxamide derivative compounds, methods of preparing the piperidine-3-carboxamide derivative compounds and piperidine-3-carboxamide derivative compounds bound to a resin
Substituted oxazoles and thiazoles derivatives as hPPARγ and hPPARα activators
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, (2008/06/13)
The present invention discloses compounds of formula (I), and tautomeric forms, pharmaceutically acceptable salts, or solvates thereof. Preferably, the compounds of the invention are dual activators of hPPARγ and hPPAR{acute over (α)}.
N-(2-benzoylphenyl)-L-tyrosine PPARγ agonists. 2. Structure-activity relationship and optimization of the phenyl alkyl ether moiety
Collins, Jon L.,Blanchard, Steven G.,Boswell, G. Evan,Charifson, Paul S.,Cobb, Jeff E.,Henke, Brad R.,Hull-Ryde, Emily A.,Kazmierski, Wieslaw M.,Lake, Debra H.,Leesnitzer, Lisa M.,Lehmann, Jürgen,Lenhard, James M.,Orband-Miller, Lisa A.,Gray-Nunez, Yolanda,Parks, Derek J.,Plunkett, Kelli D.,Tong, Wei-Qin
, p. 5037 - 5054 (2007/10/03)
We previously reported the identification of (2S)-((2- benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4- yl)ethoxy]phenyl}propanoic acid (2) (PPARγ pK(i) = 8.94, PPARγ pEC50 = 9.47) as a potent and selective PPARγ agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPARγ agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2- benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4- yl)ethoxy]phenyl}propionic acid (16) (PPARγ pK(i) = 8.85, PPARγ pEC50 = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4- {2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}phenyl)propionic acid (24) (PPARγ pK(i) = 8.66, PPARγ pEC50 = 8.89) provided two potent and selective PPARγ agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPARγ ligands (PPARγ pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPARγ binding, functional activity, selectivity, and aqueous solubility.
