SYNTHESIS AND IN-SILICO ANTI-INFLAMMATORY INVESTIGATION OF 2, 3-DIHYDROCHROMEN-4-ONE AND 3, 4-DIHYDROBENZO[B]OXEPIN-5(2H)-ONE BASED PYRAZOLE DERIVATIVES

This study synthesized six pyrazole derivatives from the key intermediates 2,3-dihydrochromen-4-one and 3,4-dihydrobenzo[b]oxepin-5(2H)-one. We have characterized all pyrazole derivatives as well as conducted in silico anti-inflammatory studies. The DFT calculations were performed using Gaussian 09 software. The compound 9 has the lowest energy gap (∆E, 1.0698 eV), lowest hardness (0.5349 eV), highest softness (1.8695 eV), and highest electrophilicity (7.0809eV) among all pyrazole derivatives and standard Aspirin. Swiss ADME software was used to carry out the ADME analysis. The chloro-substituted pyrazole derivatives (5, 6, and 9) were non-toxic, however, the nitrogen-substituted pyrazole derivatives (10, 13 and 14) and Aspirin were toxic. The docking patterns of the pyrazole derivatives with COX-2 selective inhibitors proteins (5F19) have been studied. Compound 9 has the lower binding energy (-10.2Kcal/mol) as compared with that of other pyrazole derivatives and standard Aspirin drugs. As a result, the pyrazole derivatives compound 9 is a promising anti-inflammatory drug with selective COX-2 inhibition as compared to the Aspirin drugs physicochemical properties.