676233-03-7

Upstream product

• 4637-24-5 N,N-dimethyl-formamide dimethyl acetal 
• 2881-83-6 ethyl 4-methoxybenzoylacetate 
• 94-30-4 ethyl 4-methoxybenzoate 

Downstream Products

• 676233-19-5 5-(4-methoxy-phenyl)-1-(4-sulfamoyl-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester 
• 676233-10-6 1-(4-methanesulfonyl-phenyl)-5-(4-methoxy-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester 
• 676233-33-3 5-(4-methoxy-phenyl)-1-(4-sulfamoyl-phenyl)-1H-pyrazole-4-carboxylic acid 

Relevant academic research and scientific papers

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds

Targeting the protein-protein interaction (PPI) between nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) is a potential therapeutic strategy to control diseases involving oxidative stress. Here, six classes of known small-molecule Keap1-Nrf2 PPI inhibitors were dissected into 77 fragments in a fragment-based deconstruction reconstruction (FBDR) study and tested in four orthogonal assays. This gave 17 fragment hits of which six were shown by X-ray crystallography to bind in the Keap1 Kelch binding pocket. Two hits were merged into compound 8 with a 220-380-fold stronger affinity (Ki = 16 μM) relative to the parent fragments. Systematic optimization resulted in several novel analogues with Ki values of 0.04-0.5 μM, binding modes determined by X-ray crystallography, and enhanced microsomal stability. This demonstrates how FBDR can be used to find new fragment hits, elucidate important ligand-protein interactions, and identify new potent inhibitors of the Keap1-Nrf2 PPI.

4-Substituted 1,5-diarylpyrazole, analogues of celecoxib: Synthesis and preliminary evaluation of biological properties

A number of 5-aryl-1-[4-(methylsulfonyl)-phenyl]-1H-pyrazoles and 4-(5-aryl-1H-pyrazol-1-yl)benzenesulfonamides 3, 4, 5, 6, analogues of the COX-2 selective inhibitor celecoxib (celebrex), were synthesized. In order to verify the effects on the biological properties of certain substituents put on position 4 of the pyrazole nucleus, some of these compounds were screened in vivo for their anti-inflammatory and analgesic activities. Moreover, sodium salts of carboxylic acids 4 were tested in vitro for their platelet anti-aggregating properties. The results of these preliminary biological assays showed that new derivatives are not endowed with improved anti-inflammatory and analgesic properties, in comparison with celecoxib. In addition, docking studies were carried out on the most significative compounds to evaluate their interaction mode at the active site of both COX-1 and COX-2. Some remarks about the SAR of this class of COX-inhibitors are drown out.