943834-07-9

Upstream product

• 32140-83-3 4-(4-methoxyphenyl)-3,4-dihydrocoumarin 
• 29260-03-5 ethyl (E)-3-phenoxypropenoate 
• 108-95-2 phenol 
• 200055-89-6 4-(4-toluenesulfonyloxy)coumarin 
• 170456-76-5 4-(4-methoxyphenyl)coumarin 
• 5720-07-0 4-methoxyphenylboronic acid 

Downstream Products

• 943834-08-0 4-(4-butoxy-phenyl)-chroman-2-one 

Relevant academic research and scientific papers

Lewis acid-catalyzed annulative partial dimerization of 3-aryloxyacrylates to 4-arylchroman-2-ones: Synthesis of analogues of tolterodine, RORγ inhibitors and a GPR40 agonist

A beguiling annulative partial dimerization of 3-aryloxyacrylates to 4-arylchroman-2-ones catalyzed by Lewis acid (BF3·OEt2) has been developed. The reaction involves two molecules of 3-aryloxyacrylate, resulting in the loss of one propiolate molecule to furnish 4-arylchroman-2-one, an important structural motif found in many natural products. This methodology has been elaborated to synthesize analogues of tolterodine, RORγ inhibitors and a GPR40 agonist.

GPR40 AGONISTS

The invention is directed to compounds of Formula (I) useful as GPR40 agonists. Pharmaceutical compositions and methods of treating one or more conditions including, but not limited to, insulin resistance, hyperglycemia, obesity, diabetes such as NIDDM, and other disorders related to lipid metabolism, energy homeostasis, and complications thereof, using compounds of the invention are also described.

Synthesis and biological evaluation of 3-aryl-3-(4-phenoxy)-propionic acid as a novel series of G protein-coupled receptor 40 agonists

High-throughput screening of a subset of the J&J compound library containing the carboxylic acid functional group uncovered a bromophenyl derivative as a moderate potent GPR40 agonist. Chemical elaboration of this bromophenyl led to the discovery of a novel series of GPR40 agonists with submicromolar potency. Among them, 22 and 24 behaved as full agonists when compared to the endogenous GPR40 ligand linolenic acid in a functional Ca +2 flux assay in HEK cells expressing GPR40 receptor. Several GPR40 agonists have also demonstrated the ability to induce glucose-mediated insulin secretion in the mouse MIN6 pancreatic β-cell line. Our data supports the hypothesis that GPR40 may play an important role in fatty acid-mediated glucose-dependent insulin secretion. Compound 22 exhibited good pharmacokinetic profile in rat and may serve as a good candidate for in vivo study and may help to determine if GPR40 agonists would be beneficial in the treatment of type II diabetes.