922151-74-4

Upstream product

• 1072-72-6 Tetrahydrothiopyran-4-one 
• 29683-23-6 tetrahydrothiopyran-4-ol 
• 7463-51-6 4-bromo-3,5-dimethylphenol 

Downstream Products

• 1453862-22-0 4-(4-bromo-3,5-dimethylphenoxy)tetrahydro-2H-thiopyran 1,1-dioxide 
• 1453861-51-2 ethyl 2-(3-(4-((4'-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxetan-3-yl)acetate 
• 1453861-52-3 2-(3-(4-((4'-((1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy)-2',6'-dimethyl-[1,1'-biphenyl]-3-yl)methoxy)phenyl)oxetan-3-yl)acetic acid 
• 922151-76-6 [2,6-dimethyl-4-(tetrahydro-2H-thiopyran-4-yloxy)phenyl]boronic acid 
• 1373551-51-9 [(3R)-6-({4'-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid 
• 1373551-50-8 methyl [(3R)-6-({4'-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate 
• 1373551-49-5 [6-({4'-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy]-2',6'-dimethylbiphenyl-3-yl}methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetic acid 
• 1373551-48-4 methyl [6-({'-[(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)oxy]-2',6'-dimethylbiphenyl-3-yl}-methoxy)-2,3-dihydro-1-benzofuran-3-yl]acetate 

Relevant academic research and scientific papers

CARBOXYLIC ACID COMPOUNDS IN TREATMENT OF DIABETES MELLITUS

The invention relates to compounds for increasing GPR40 recetpor activity and application thereof. These compounds include of a compound of Formula (I), pharmaceutically acceptable salts thereof, solvates thereof, isomers thereof, or produgs of the compou

PHENYL ALKANOIC ACID DERIVATIVES AS GPR AGONISTS

The present invention relates to phenyl alkanoic acid derivatives (the compounds of Formula (I)); and their isotopic forms, stereoisomeric and tautomeric forms and mixtures thereof in all ratios, or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, prodrugs, polymorphs, N-oxides, S-oxides or carboxylic acid isosteres thereof. The invention also relates to processes for the preparation of compounds of Formula (I) and pharmaceutical compositions comprising one or more of the compounds of Formula (I). The said compounds and the pharmaceutical composition function as GPR (G-protein coupled receptor) agonists, particularly as GPR40 agonists, and are useful in the treatment of diseases or conditions mediated by GPR40. The present invention further relates to a method of treatment of diseases or conditions mediated by GPR40comprising administering to a subject in need thereof a therapeutically effective amount of the compounds of Formula (I).

Optimization of (2,3-dihydro-1-benzofuran-3-yl)acetic acids: Discovery of a non-free fatty acid-like, highly bioavailable G protein-coupled receptor 40/free fatty acid receptor 1 agonist as a glucose-dependent insulinotropic agent

G protein-coupled receptor 40 (GPR40)/free fatty acid receptor 1 (FFA1) is a free fatty acid (FFA) receptor that mediates FFA-amplified glucose-stimulated insulin secretion in pancreatic β-cells. We previously identified (2,3-dihydro-1-benzofuran-3-yl)acetic acid derivative 2 as a candidate, but it had relatively high lipophilicity. Adding a polar functional group on 2 yielded several compounds with lower lipophilicity and little effect on caspase-3/7 activity at 30 μM (a marker of toxicity in human HepG2 hepatocytes). Three optimized compounds showed promising pharmacokinetic profiles with good in vivo effects. Of these, compound 16 had the lowest lipophilicity. Metabolic analysis of 16 showed a long-acting PK profile due to high resistance to β-oxidation. Oral administration of 16 significantly reduced plasma glucose excursion and increased insulin secretion during an OGTT in type 2 diabetic rats. Compound 16 (TAK-875) is being evaluated in human clinical trials for the treatment of type 2 diabetes.

FUSED CYCLIC COMPOUNDS

The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof. The compound or a salt thereof or a prodrug thereof has a GPR40 receptor function modulating action and is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

CYCLOPROPANECARBOXYLIC ACID COMPOUND

A compound of the formula (I): wherein each symbol is as defined in the description, a salt thereof, and a prodrug thereof of the present invention unexpectedly have a superior GPR40 receptor agonist activity and superior properties as pharmaceutical prod