304648-23-5Relevant academic research and scientific papers
Synthesis and SAR/3D-QSAR studies on the COX-2 inhibitory activity of 1,5-diarylpyrazoles to validate the modified pharmacophore
Singh, Sunil K.,Saibaba,Rao, K. Srinivasa,Reddy, P. Ganapati,Daga, Pankaj R.,Rajjak, S. Abdul,Misra, Parimal,Rao, Y. Koteswar
, p. 977 - 990 (2007/10/03)
Diverse analogs of 1,5-diarylpyrazoles having 3-hydroxymethyl-4-sulfamoyl (SO2NH2)/methyl sulfonyl (SO2Me)-pheny group at N1 were synthesized and evaluated for their in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The SAR study mainly involved the variations at positions C-3, C-5 and N1 of the pyrazole ring. Several small hydrophobic groups at/around position-4 of C-5 phenyl, viz. 3,4-dimethylphenyl analog 9, 3-methyl-4-methylsulfanylphenyl analog 14 and 2,3-dihydrobenzo[b] thiophenyl analog 17, exhibited impressive COX-2 inhibitory potency. In general, the sulfonamide analogues with a CHF2 at C-3 were found to be more potent than those having a CF3 group. The three dimensional quantitative structure activity relationship comprising comparative molecular field analysis (3D-QSAR-CoMFA) afforded the models with high predictivity which further validated the acceptance of hydroxymethyl (CH2OH) group in the hydrophilic pocket of the COX-2 enzyme.
Polar substitutions in the benzenesulfonamide ring of celecoxib afford a potent 1,5-diarylpyrazole class of COX-2 inhibitors
Singh, Sunil K.,Reddy, P. Ganapati,Rao, K. Srinivasa,Lohray, Braj B.,Misra,Rajjak, Shaikh A.,Rao, Yeleswarapu K.,Venkateswarlu
, p. 499 - 504 (2007/10/03)
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.
