637352-45-5

Upstream product

• 600-00-0 ethyl 2-bromoisobutyrate 
• 15174-69-3 4-hydroxy-3-methyl-benzaldehyde 

Downstream Products

• 637352-40-0 ethyl 2-methyl-2-[2-methyl-4-({[4-(trifluoromethyl)benzyl]amino}methyl)phenoxy]propanoate 
• 1348381-87-2 Example 38 
• 639783-92-9 2-methyl-2-[2-methyl-4-{[(4-methyl-2-[4-trifluoromethylphenyl]-thiazol-5-YLMETHYL)-N-(3-METHOXYPROPYL)-AMINO]METHYL}PHENOXY]PROPIONIC ACID 
• 639783-73-6 Example 45 
• 639783-65-6 example 29 
• 639783-90-7 2-METHVL-2-[2-METHYL-4-{[ (4-METHYL-2-[4-TRIFLUOROMETHYLPHENYL]-THIAZOL-5-ylmethyl)-N-(propen-2-yl)-amino]methyl}phenoxy]propionic acid 
• 1346857-25-7 Example 27 
• 639783-82-7 2-methyl-2-[2-methyl-4-(((1-methyl-3-(4-trifluoromethylphenyl))-pyrazol-5-yl) methyl-N-propyl-aminomethyl) phenoxy] propionic acid 
• 1347110-41-1 Example 28 
• 1347123-74-3 Example 40 
• 1347726-02-6 Example 25 
• 639783-81-6 Example 57 
• 1348756-53-5 Example 53 
• 1026055-55-9 2-methyl-2-[2-methyl-4-((3-(4-trifluoromethyl-phenyl)-[1,2,4]-oxadiazol-5-YL) METHYL-N-METHYL-AMINOMETHYL) PHENOXY] propionic acid 

Relevant academic research and scientific papers

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.

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

SUBSTITUTED PYRAZOLES AS PPAR AGONISTS

A compound of formula (I) and pharmaceutically acceptable salts, solvates and hydrolysable esters thereof (I) wherein: p is O or 1; q is O or 1; R1 and R2 are independently H or C1-3 alkyl; R3 and R4 are independently H, C1-6 alkyl, -OC1-6 alkyl, halogen, OH, C2-6 alkenyl or CF3; R5 is H, C1-6 alkyl (optionally substituted by one or more halogens, -COphenyl, OC1-6 alkyl, phenyl morpholino or C2-6 alkenyl. R6 is C1-6 alkyl, halogen, -OCH2 phenyl, phenyl (optionally substituted by C1-3 alkiyl), morpholino, pyrrolidino, piperidino, thiophenyl, furanyl pyridinyl or -OC2-6 alkenyl. These compounds activate the alpha and gamma subtypes fo the hppar receptor and are useful e.g. in the treatment of diabetes, dyslipidemia or syndrome X.

CHEMICAL COMPOUNDS

A compound of formula (I) or a pharmaceutically acceptable salt, solvate, or hydrolysable ester thereof, wherein: (...).

CHEMICAL COMPOUNDS

A compound of formula (I) or a pharmaceutically acceptable salt, solvate, or hydrolysable ester thereof, .Wherein:R1 and R2 are independently hydrogen or C1-3 alkyl;X represents a bond, CH2 or O;R3 and R4 are independently hydrogen, C1-6 alkyl, OCH3, CF3, allyl or halogen;X1 is CH2, SO2, or CO;R5 is -C1-6 alkyl (optionally substituted by C1-6alkoxy or C1-6alkylthio), -C2-6 alkenyl, -C0-6 alkyl phenyl (wherein the phenyl is optionally substituted by one or more CF3, halogen, C1-3 alkyl, C1-3 alkoxy), -COC1-6 alkyl, SO2C1-6 alkyl ;R6 is phenyl or a 6 membered heteroaryl group containing 1,2 or 3 N atoms wherein the phenyl or heteroaryl group is optionally substituted with 1, 2 or 3 moieties selected from the group consisting of C1-6 alkyl, halogen, -OC1-6 alkyl, -SO2C1-3 alkyl, phenyl (optionally substituted by one or more groups selected from halogen, CF3, C1-3 alkyl, OC1-3 alkyl, acetyl, CN).