196810-82-9

Usage

Chemical structure

Contains both imidazole and phenyl moieties

Neurotoxin

Linked to Parkinson's disease

Mechanism

Selectively toxic to dopamine-producing neurons in the brain, leading to cell degeneration and Parkinson's symptoms

Research use

Used to induce Parkinson's-like symptoms in animal models and study the disease's underlying mechanisms

Legal status

Highly controlled substance, not used in medical treatments

Upstream product

• 2411-77-0 N-methyl-4-phenylimidazole 
• 157-18-6 oxirene 
• 670-95-1 4-Phenylimidazole 
• 75-21-8 oxirane 

Downstream Products

• 1438258-14-0 5-bromo-2-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one 
• 1438258-15-1 2-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethyl)-5-morpholino-[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one 

Relevant academic research and scientific papers

TRIAZOLOPYRIDINONE PDE10 INHIBITORS

The present invention is directed to triazolopyridinone compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

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.