196810-26-1

Upstream product

• 3424-93-9 4-methoxyphenylacetamide 
• 105983-77-5 methyl 4-bromo-3-oxopentanoate 
• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 

Downstream Products

• 136058-71-4 4-(2-p-Methoxyphenyl-5-methyloxazol-4-ylethoxy) benzaldehyde 
• 136058-69-0 2-[2-(4-methoxyphenyl)-5-methyl-oxazol-4-yl]-ethanol 

Relevant academic research and scientific papers

Substituted oxazoles and thiazoles derivatives as hPPARγ and hPPARα activators

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

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.

Azole phenoxy hydroxyureas as selective and orally active inhibitors of 5- lipoxygenase

Azole phenoxy hydroxyureas are a new class of 5-lipoxygenase (5-LO) inhibitors. Structure-activity relationship studies have demonstrated that electronegative substituents on the 2-phenyl portion of the oxazole tail increased the ex vivo potency of these