678987-46-7

Upstream product

• 720-94-5 4,4,4-trifluoro-1-(4-methylphenyl)butane-1,3-dione 
• 122-00-9 para-methylacetophenone 
• 910303-54-7 (Z)-1,1,1-trifluoro-4-hydroxy-4-(4-methylphenyl)-but-3-en-2-one 

Relevant academic research and scientific papers

LARGE CONDUCTANCE CALCIUM-ACTIVATED K CHANNEL OPENER

The present invention provides a large conductance calcium-activated K channel opener comprising a compound of the formula (I): wherein R1 and R3 are each sulfonamide, carbamoyl, acyl, amino, and the like, m and n are each 0 to 2, R2 and R4 are each cyano, nitro, hydroxyl, an alkoxy, a halogen, or an alkyl, Ring A is benzene or a heterocyclic ring, Ring B is benzene, a heterocyclic ring, a cycloalkane etc, and Ring Q is pyrazole or isoxazole, or a pharmaceutically acceptable salt thereof as an active ingredient.

2-Hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl] -1-benzenesulfonamide (DRF-4367): An orally active COX-2 inhibitor identified through pharmacophoric modulation

Analogs of 1,5-diarylpyrazoles with a novel pharmacophore at N1 were designed, synthesized and evaluated for the in-vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The variations at/around position-4 of the C-5 phenyl ring in conjunction with a CF3 and CHF2 groups at C-3 exhibited a high degree of potency and selectivity index (SI) for COX-2 inhibition. The in-vivo evaluation of these potent compounds with a few earlier ones indicated the 4-OMe-phenyl analog 6 and the 4-NHMe-phenyl analog 9 with a CF3, and the 4-OEt-phenyl analog 19 with a CHF2 group at C-3 to possess superior potency than celecoxib. In addition to its impressive anti-inflammatory, antipyretic, analgesic and anti-arthritic properties, compound 6 (DRF-4367) was found to possess an excellent pharmacokinetic profile, gastrointestinal (GI) safety in the long-term arthritis study and COX-2 potency in human whole blood assay. Thus, compound 6 was selected as an orally active anti-inflammatory candidate for pre-clinical evaluation.

Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors

Several chemical modifications in the N1-benzenesulfonamide ring of celecoxib are presented. The series with a hydroxymethyl group adjacent to the sulfonamide was found to be the most potent modification that yielded many compounds selectively active against COX-2 enzyme in vitro.