51336-35-7

Upstream product

• 123-08-0 4-hydroxy-benzaldehyde 
• 600-00-0 ethyl 2-bromoisobutyrate 

Downstream Products

• 639784-48-8 ETHYL-2-METHYL-2-[(4-(N-(2,2,2-trifluoroethyl)aminomethyl)phenoxy)]-propanoate 
• 639784-43-3 ethyl 2-[4-(hydroxymethyl)phenoxy]-2-methylpropanoate 
• 639783-72-5 Example 44 
• 639783-91-8 2-METHYL-2-[4-{[ (4-METHYL-2-[4-TRIFLUOROMETHYLPHENYL]-THIAZOL-5-YLMETHYL)-N-(2-METHOXYETHYL)-AMINO]METHYL}PHENOXY]PROPIONIC ACID 
• 639783-89-4 2-METHYL-2-[4-{[(4-METHYL-2-[4-TRIFLUOROMETHYLPHENYL]-THIAZOL-5-YLMETHYL)-N-(propen-2-yl)-amino]methyl}phenoxy]propionic acid 
• 1347730-66-8 Example 39 
• 1347719-01-0 24 
• 1027251-82-6 2-methyl-2-[4-{[(4-methyl-2-[4-trifluoromethylphenyl]-thiazol-5-ylmethyl)-N-methyl-amino]methyl}phenoxy]propionic acid 
• 639783-80-5 Example 56 
• 639784-56-8 2-methyl-2-(4-methylaminomethyl-phenoxy)-propionic acid ethyl ester 
• 85212-83-5 2-(4-formylphenoxy)-2-methylpropanoic acid 

Relevant academic research and scientific papers

Microwave-assisted efficient synthesis of pyrazole-fibrate derivatives as stimulators of glucose uptake in skeletal muscle cells

The design and synthesis of a series of pyrazolo[3,4-d]pyrimidinones containing fibrate side chains have been accomplished by utilizing the concept of molecular hybridization. All the synthesized compounds were evaluated for the glucose uptake stimulatory effect in L6 rat skeletal muscle cells. Four compounds (3f, 3g, 3j and 3q) were found to show significant stimulation of glucose uptake. Further these four compounds have been examined for their Glut4 translocation stimulatory effect in L6-Glut4myc myotubes. Compound 3q was found to exert maximum increase in GLUT4myc translocation.

PYRROLIDINE DERIVATIVES AS PPAR AGONISTS

The present invention discloses a class of pyrrolidine derivatives as PPAR agonist, and their use for the treatment of some diseases of PPAR receptor-associated pathways (such as nonalcoholic steatohepatitis and concurrent fibrosis, insulin resistance, primary biliary cholgangitis, dyslipidenmia, hyperlipidemia, hypercholesterolemia, atherosclerosis, hypertriglyceridemia, cardiovascular disease, obesity or the like). In particular, the present invention discloses a compound represented by Formula (I) or a pharmaceutically acceptable salt thereof.

Discovery of novel allosteric site and covalent inhibitors of FBPase with potent hypoglycemic effects

Fructose-1,6-bisphosphatase (FBPase) is an essential enzyme of GNG pathway. Significant advances demonstrate the FBPase plays a critical role in treatment of diabetes. Numerous FBPase inhibitors were developed by targeting AMP site, nevertheless, none of these inhibitors has exhibited suitable potency and druggability. Herein, a new allosteric site (C128) on FBPase was discovered, and several nitrostyrene compounds exhibiting potent FBPase inhibitions were found covalently bind to C128 site on FBPase. Mutagenesis suggest that C128 is the only cysteine that can influence FBPase inhibition, the N125–S124–S123 pathway was most likely involved in allosteric signaling transmission between C128 and active site. However, these nitrostyrenes may bind with multiple cysteine besides C128 in FBPase. To improve pocket selectivity, a series of novel compounds (14a-14n) were re-designed rationally by integrating fragment-based covalent virtual screening and machine-learning-based synthetic complexity evaluation. As expected, the mass spectrometry validated that the proportion of title compounds binding to the C128 in FBPase was significantly higher than that of nitrostyrenes. Notably, under physiological and pathological conditions, the treatment of compounds 14b, 14c, 14i or 14n led to potent inhibition of glucose production, as well as decreased triglyceride and total cholesterol levels in mouse primary hepatocytes. We highlight a novel paradigm that molecular targeting C128 site on FBPase can have potent hypoglycemic effect.

NOVEL COMPOUND HAVING SKIN-WHITENING, ANTI-OXIDIZING AND PPAR ACTIVITIES AND MEDICAL USE THEREFOR

Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.

Indole-based fibrates as potential hypolipidemic and antiobesity agents

Hypolipidemic and antiobesity effects of the newly synthesized indole-based fibrates were evaluated in Triton WR-1339 and high fat diet (HFD)-induced hyperlipidemic rats. Preliminary screening of all the synthesized compounds was done by using an acute model (Triton model), in which compounds 3f and 3l showed significant antidyslipidemic activity. Furthermore, these compounds 3f and 3l were found to induce significant weight loss in the visceral fat mass of HFD-fed hyperlipidemic rats without affecting the normal feeding behavior. Histological examination of the liver of rats supplemented with 3f and 3l revealed a significant decrease in steatosis when compared to the effect of the standard drug fenofibrate. Additional effects such as an increase in lecithin cholesterol acyl-transferase (LCAT) enzyme level and increased receptor mediated catabolism of I131-low density lipoproteins (LDL) confirm and reinforce the efficacy of both of these compounds as a new class of dual-acting hypolipidemic and antiobesity agents.

Design, synthesis and evaluation of novel zwitterionic compounds as PPARα/γ dual agonists (1)

We describe here the design, syntheses and structure-activity relationships (SAR) of novel zwitterionic compounds as non-thiazolidinedion (TZD) based peroxisome proliferator activated receptor (PPAR) α/γ dual agonists. We commenced the medicinal research

PHENOXYACETIC ACID DERIVATIVES AND DRUGS USING THE SAME

It is intended to provide a novel compound having an excellent agonism to PPARs α/γ and desirable properties as a drug. An agonist to peroxisome proliferator-activated receptors α/γ which is represented by the general formula (I) (wherein Q represents an optionally substituted benzene ring or pyridine ring; R1 and R2 represent each an optionally substituted phenyl group or a 5- to 6-membered aromatic heterocycle group; X, Y and Z independently represent each C, O, S or N; R3 to R9 represent each a hydrogen atom, a lower alkyl group, etc.; and n is an integer of from 0 to 3.

Substituted 2-[(4-aminomethyl)phenoxy]-2-methylpropionic acid PPARα agonists. 1. Discovery of a novel series of potent HDLc raising agents

The peroxisome proliferator activated receptors PPARα, PPARγ, and PPARδ are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPARα agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPARα agonists. Modification of the selective PPARδ agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPARα agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPARα and at least 500-fold selectivity versus PPARγ and PPARγ. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

PHENOXYACETIC ACID DERIVATIVE AND MEDICINE CONTAINING THE SAME

Novel compounds having excellent PPAR α/γ agonist effects and having desirable properties for medicaments are provided. Peroxisome proliferator-activated receptor α/γ agonists of the general formula (I): (wherein Q is an optionally-substituted benzene or

1,2-BIS-(SUBSTITUTED-PHENYL)-2-PROPEN-1-ONES AND PHARMACEUTICAL COMPOSITIONS THEREOF

The invention relates to compounds, pharmaceutical compositions and methods of using compounds of the general formula (I), or its pharmaceutically acceptable salt or ester, wherein the substituents are defined in the application.