Synthesis of N-benzenesulfonamide-1H-pyrazoles bearing arylsulfonyl moiety: Novel celecoxib analogs as potent anti-inflammatory agents

The reaction of arylsulfones 11a-d with hydrazonoyl chloride derivative 13 furnished celecoxib analogs 4-(3-acetyl-5-aryl-4-(arylsulfonyl)-1H-pyrazol-1-yl)benzenesulfonamides 15a-d, respectively. Oximes 16a, b and hydrazones 17a, b were prepared by reacting sulfones 11a, b with hydroxyl amine and phenyl hydrazine, respectively. The anti-inflammatory activity of the synthesized compounds showed that, 5-(4-bromophenyl)-4-(phenylsulfonyl)pyrazole 15c and 5-(4-bromophenyl)-4-(4-tolylsulfonyl)pyrazole 15d exhibited excellent anti-inflammatory activity with ED50 = 68 +/- 2.2 and 51 +/- 0.7 mu M/kg, respectively, higher than that of celecoxib (ED50 = 86 +/- 1.1 mu M/kg) after 3 h with acceptable ulcer index. In addition, the LD50 of 15c and 15d is 7.1 mM/kg for each, and 9.8 mM/kg for celecoxib. Compound 15d appeared selectivity index (COX-2/COX-1) almost the half of celecoxib while 15c is non-selective for COX-2. Compound 15c with ED50 = 80 +/- 2.8 mu M/kg showed a significant analgesic activity when compared with celecoxib (ED50 = 70 +/- 3.9 mu M/kg) after 2 h whereas 15b (ED50 = 50 +/- 1.2 mu M/kg) and 15d (ED50 = 69 +/- 2.7 mu M/kg) seemed to be more potent than celecoxib (ED50 = 156 +/- 4.8 mu M/kg) but with a shorter duration (0.5 h). (C) 2014 Elsevier Masson SAS. All rights reserved.