74649-83-5

Upstream product

• 1269763-71-4 C₁₈H₁₇FO₃ 
• 4397-53-9 p-benzyloxybenzaldehyde 
• 59067-46-8 4-[(4-chlorobenzyl)oxy]benzaldehyde 
• 74649-82-4 ethyl 2-fluoro-3-<4-(4-chlorobenzyloxy)phenyl>acrylate 

Downstream Products

• 1269763-58-7 3-{4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]phenyl}-2-fluoropropanoic acid 
• 74649-76-6 2-fluoro-3-(4-benzyloxy)phenylpropionic acid 

Relevant academic research and scientific papers

Design, synthesis, and biological activity of potent and orally available g protein-coupled receptor 40 agonists

G protein-coupled receptor 40 (GPR40) is being recently considered to be a new potential drug target for the treatment of type 2 diabetes because of its role in the enhancement of free fatty acid-regulated glucose-stimulated insulin secretion in pancreatic β-cells. We initially identified benzyloxyphenylpropanoic acid (1b) (EC50 = 510 nM), which was designed based on the structure of free fatty acids, as a promising lead compound with GPR40 agonist activity. Chemical modification of compound 1b led to the discovery of 3-{4-[(2′,6′-dimethylbiphenyl-3-yl)methoxy]-2- fluorophenyl}propanoic acid (4p) as a potent GPR40 agonist (EC50 = 5.7 nM). Compound 4p exhibited acceptable pharmacokinetic profiles and significant glucose-lowering effects during an oral glucose tolerance test in diabetic rats. Moreover, no hypoglycemic event was observed even after administration of a high dose of compound 4p to normal fasted rats. These pharmacological results suggest that GPR40 agonists might be novel glucose-dependent insulin secretagogues with little or no risk of hypoglycemia.

PHENYLPROPANOIC ACID DERIVATIVES

The present invention provides a novel compound having a GPR40 receptor function modulating action, which is useful as an insulin secretagogue, a drug for the prophylaxis or treatment of diabetes and the like. A compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof have unexpectedly superior GPR40 receptor agonist activity and also show superior properties as a pharmaceutical product, such as stability and the like. Thus, they can be safe and useful drugs for the prophylaxis or treatment of GPR40 receptor related conditions or diseases in mammals.

Studies on antihyperlipidemic agents. II. Synthesis and biological activities of 2-chloro-3-arylpropionic acids

α-Substituted-β-arylpropionic acid derivatives were prepared and examined for hypolipidemic activity. The structure-activity relationship study showed that a chloro substituent at the α-position and an aryloxy or aralkyloxy substituent on the β-aryl moiet