600167-54-2

Upstream product

• 638-07-3 ethyl (2-chloroaceto)acetate 
• 15570-12-4 3-methoxybenzenethiol 
• 32807-28-6 Methyl 4-chloroacetoacetate 

Downstream Products

• 945774-02-7 C₂₆H₂₁F₃O₄S 
• 945774-01-6 C₂₆H₂₁F₃O₄S 
• 945773-99-9 C₂₆H₂₁F₃O₄S 
• 779199-82-5 {6-[5-(4-Trifluoromethyl-phenyl)-isoxazol-3-ylmethoxy]-benzo[b]thiophen-3-yl}-acetic acid methyl ester 
• 779198-40-2 {6-[5-(4-Chloro-phenyl)-isoxazol-3-ylmethoxy]-benzo[b]thiophen-3-yl}-acetic acid methyl ester 
• 600167-57-5 methyl 2-(6-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methoxy)benzo[b]thiophen-3-yl)acetate 

Relevant academic research and scientific papers

Discovery of phenylsulfonyl acetic acid derivatives with improved efficacy and safety as potent free fatty acid receptor 1 agonists for the treatment of type 2 diabetes

The free fatty acid receptor 1 (FFA1) has emerged as an attractive anti-diabetic target that mediates glucose-stimulated insulin secretion. Several FFA1 agonists have been reported, but many of them possessed somewhat high lipophilicity and/or molecular weight. Herein, we describe the identification of sulfone-carboxylic acid moiety with the multiple advantages of reducing lipophilicity, cytotoxicity and β-oxidation associated with compound 2. Further structure-activity relationship study based on the previleged scaffolds led to the discovery of 2-{(4-[(2’-chloro-[1,1’-biphenyl]-3-yl)methoxy]phenyl)sulfonyl}acetic acid (compound 20), which showed a better balance than compound 2 in terms of physicochemical properties, cytotoxicity profiles and pharmacokinetic properties. Subsequent in vivo studies demonstrated that compound 20 robustly improves the glucose tolerance both in normal and type 2 diabetic models without the risk of hypoglycemia. Compared to the high risk of TAK-875 induced liver toxicity, there was no significant adverse effects such as hepatic and renal toxicity were observed in the chronic toxicity studies of compound 20 even at the higher dose.

ANTIDIABETIC BICYCLIC COMPOUNDS

Diaryl ethers in which one of the aryl groups is a phenyl fused to a cycloalkyl or heterocyclic ring, to which is attached an acetic acid group, are agonists of G-protein coupled receptor 40 (GPR40) and are useful as therapeutic compounds, particularly in the treatment of Type 2 diabetes mellitus, and of conditions that often accompany this disease, including insulin resistance, obesity and lipid disorders.

Synthesis and SAR of selective benzothiophene, benzofuran, and indole-based peroxisome proliferator-activated receptor δ agonists

Recent literature has suggested the benefit of selective PPARδ agonists for the treatment of atherosclerosis and other disease states associated with the metabolic syndrome. Herein we report the synthesis and structure-activity relationships of a series of novel and selective PPARδ agonists. Our search began with identification of a novel benzothiophene template which was modified by the addition of various thiazolyl, isoxazolyl, and benzyloxy-benzyl moieties. Further elucidation of the SAR led to the identification of benzofuran and indole based templates. During the course of our research, we discovered three new chemical templates with varying degrees of affinity and potency for PPARδ versus the PPARα and PPARγ subtypes.

Compounds that modulate PPAR activity and methods of preparation

This invention relates to compounds that alter PPAR activity. The invention also relates to pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, and methods of using them as therapeutic agents for treating or preventing dyslipidemia, hypercholesterolemia, obesity, hyperglycemia, atherosclerosis, hypertriglyceridemia and hyperinsulinemia in a mammal. The present invention also relates to methods for making the disclosed compounds.

Compounds that modulate PPAR activity and methods of preparation

This invention discloses compounds that alter PPAR activity. The invention also discloses pharmaceutically acceptable salts of the compounds, pharmaceutically acceptable compositions comprising the compounds or their salts, and methods of using them as therapeutic agents for treating or preventing hyperlipidemia and hypercholesteremia in a mammal. The present invention also discloses method for making the disclosed compounds.