691902-20-2

Upstream product

• 15852-73-0 (3-Bromophenyl)methanol 
• 5597-50-2 3-(4-hydroxyphenyl)propionic acid methyl ester 
• 691902-19-9 methyl 4-[[2'-(1-methylethyl)-[1,1'-biphenyl]-3-yl]methoxy]benzenepropanoate 
• 691904-05-9 methyl 3-{4-[(3-bromobenzyl)oxy]phenyl}propanoate 
• 89787-12-2 2-isopropylphenylboronic 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.

RECEPTOR FUNCTION CONTROLLING AGENT

The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.