858096-99-8

Upstream product

• 87199-16-4 3-Formylphenylboronic acid 
• 5597-50-2 3-(4-hydroxyphenyl)propionic acid methyl ester 
• 858096-43-2 [2',6'-dimethyl-4'-(tetrahydro-2H-pyran-2-yloxy)biphenyl-3-yl]methanol 
• 858096-42-1 2',6'-dimethyl-4'-(tetrahydro-2H-pyran-2-yloxy)biphenyl-3-carbaldehyde 
• 858096-41-0 2-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-pyran 

Downstream Products

• 1392503-26-2 methyl 3-{4-[(4'-methoxy-2',6'-dimethylbiphenyl-3-yl)methoxy]phenyl}propanoate 

Relevant academic research and scientific papers

Discovery of phenylpropanoic acid derivatives containing polar functionalities as potent and orally bioavailable G protein-coupled receptor 40 agonists for the treatment of type 2 diabetes

As part of a program to identify potent GPR40 agonists with drug-like properties suitable for clinical development, the incorporation of polar substituents was explored with the intention of decreasing the lipophilicity of our recently disclosed phenylpropanoic acid derivative 1. This incorporation would allow us to mitigate the cytotoxicity issues observed with compound 1 and enable us to move away from the multifunctional free fatty acid-like structure. Substitutions on the 2′,6′-dimethylbiphenyl ring were initially undertaken, which revealed the feasibility of introducing polar functionalities at the biphenyl 4′-position. Further optimization of this position and the linker led to the discovery of several 4′-alkoxybiphenyl derivatives, which showed potent GPR40 agonist activities with the best balance in terms of improved cytotoxicity profiles and favorable pharmacokinetic properties. Among them, 3-{2-fluoro-4-[({4′-[(4-hydroxy-1,1-dioxidotetrahydro-2H-thiopyran- 4-yl)methoxy]-2′,6′-dimethylbiphenyl-3-yl}methyl)amino]phenyl} propanoic acid (35) exhibited a robust plasma glucose-lowering effect and insulinotropic action during an oral glucose tolerance test in rats with impaired glucose tolerance.

3-(4-BENZYLOXYPHENYL)PROPANOIC ACID DERIVATIVES

The present invention provides a novel compound represented by the formula (I) wherein each symbol is as defined in the specification, a salt thereof and a prodrug thereof having a superior GPR40 receptor function modulating action, which can be used as an insulin secretagogue, an agent for the prophylaxis or treatment of diabetes and the like. They unexpectedly show 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 pharmaceutical agents for the prophylaxis or treatment of GPR40 receptor related diseases in mammals.