title: 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).
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Department of Applied Organic Chemistry, National Research Center, Dokki, Cairo 12622, Egypt. Electronic address: hatem_741@yahoo.com.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Abdel-Aziz
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: Al-Rashood
authors.affiliation: Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
authors.forename: Kamal Eldin H
authors.initials: KE
authors.lastname: ElTahir
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt.
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Suddek
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000068579:Celecoxib; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013449:Sulfonamides / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011720:Pyrazoles; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib
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