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

Abstract

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 μM/kg, respectively, higher than that of celecoxib (ED50 = 86 ± 1.1 μM/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 μM/kg showed a significant analgesic activity when compared with celecoxib (ED50 = 70 ± 3.9 μM/kg) after 2 h whereas 15b (ED50 = 50 ± 1.2 μM/kg) and 15d (ED50 = 69 ± 2.7 μM/kg) seemed to be more potent than celecoxib (ED50 = 156 ± 4.8 μM/kg) but with a shorter duration (0.5 h).

Keywords: Anti-inflammatory activity; Cyclooxygenase inhibitors; DITVWQPTRBYVRP-UHFFFAOYSA-N; DREVPGKOIZVPQV-UHFFFAOYSA-N; HBZUALMGOGLJFP-UHFFFAOYSA-N; IOWCJCHJZDLKMN-NXVVXOECSA-N; JGMRIHQYBXLTGM-UHFFFAOYSA-N; JJZAFNLTCGWRGB-UHFFFAOYSA-N; JWHMVCXCZLETGB-UHFFFAOYSA-N; KISJEJKQXLRPPO-UHFFFAOYSA-N; KLKFNBIIVIGNCB-UHFFFAOYSA-N; N-benzenesulfonamide-1H-pyrazoles; Sulfones; Ulcerogenic activity; WVUQXZSJMSIFGV-PFONDFGASA-N; YUBACKPNNQKHMP-LNVKXUELSA-N; YYLNVVCNNQZCEK-XDOYNYLZSA-N.