691902-33-7

Upstream product

• 691902-32-6 ethyl 3-[4-[(2',6'-dimethylbiphenyl-3-yl)methoxy]-2-fluorophenyl]propionate 
• 691904-78-6 3-(2-fluoro-4-hydroxyphenyl)propanoic acid ethyl ester 
• 691905-27-8 (2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methanol 
• 691905-26-7 2',6'-dimethyl-[1,1'-biphenyl]-3-carbaldehyde 
• 3132-99-8 m-bromobenzoic aldehyde 
• 100379-00-8 2,6-dimethylbenzene boronic acid 
• 331-64-6 2-fluoro-4-methoxy-benzaldehyde 

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.

Remedy for Diabetes

The present invention relates to a therapeutic agent for diabetes with sulfonylurea secondary failure, which contains a GPR40 agonist. According to the present invention, a therapeutic agent for diabetes with sulfonylurea secondary failure that affords a superior insulin secretion effect and a superior hypoglycemic effect even in diabetic patients for whom a sulfonylurea compound or a fast-acting insulin secretagogue fails to provide an insulin secretion effect and therefore, fails to provide a sufficient hypoglycemic effect can be provided.