476156-34-0

Upstream product

• 186552-02-3 (4-cyano-2-methylphenoxy)acetic acid methyl ester 
• 15174-69-3 4-hydroxy-3-methyl-benzaldehyde 
• 96-32-2 bromoacetic acid methyl ester 
• 96-34-4 methyl chloroacetate 
• 162922-16-9 4-hydroxy-2-methylphenoxyacetic acid 
• 317319-10-1 methyl (4-hydroxy-2-methylphenoxy)acetate 

Downstream Products

• 870195-27-0 [4-(hydroxyimino-methyl)-2-methyl-phenoxy]-acetic acid methyl ester 
• 870195-29-2 (4-{4-[2-(2,4-dichloro-phenoxy)-ethyl-carbamoyl]-5-phenyl-isoxazol-3-yl}-2-methyl-phenoxy)-acetic acid methyl ester 

Relevant academic research and scientific papers

Discovery of novel dual PPARα/δ agonists based on benzimidazole scaffold for the treatment of non-alcoholic fatty liver disease

Many peroxisome proliferator-activated receptors (PPARs) agonists have been developed for the treatment of metabolic disorders, while several PPARs agonists were discontinued in clinical trials because of PPARγ related side effects. In order to increase the selectivity against PPARγ, we performed a structure-activity relationship study based on PPARα/γ/δ agonist MHY2013. These efforts eventually led to the identification of compound 4, a dual PPARα/δ agonist with considerable potencies on PPARα/δ and high selectivity against PPARγ. In the Western Diet and CCl4-induced non-alcoholic steatohepatitis model, compound 4 alleviates the hepatic steatosis, inflammation, and fibrosis. These results indicated that dual PPARα/δ agonist 4 might be a promising lead compound for further investigations.

3,4,5-Trisubstituted isoxazoles as novel PPARδ agonists. Part 2

A series of PPARδ-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARδ agonist with good in vivo PK properties in mouse (Cmax = 5.1 μM, t1/2 = 3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARδ is discussed.

COMPOUNDS AND COMPOSITIONS AS PPAR MODULATORS

The invention provides compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPAR .