New celecoxib derivatives as anti-inflammatory agents.
A series of 1,5-diarylpyrazoles with a substituted benzenesulfonamide moiety was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Some compounds, for example, (+/-)-2-[4-(5- p-tolyl-3-trifluoromethyl-pyrazole-1-yl)-benzenesulfonylaminooxy]-propionic acid 16 and its disodium salt 21, had a higher in vivo anti-inflammatory activity compared to celecoxib, despite having no in vitro COX-1 or COX-2 inhibitory activity. Their gastrointestinal side effect profile is essentially more favorable than that of celecoxib.
Szabó
György
G
Medicinal Chemistry Research Laboratory and Department of Pharmacology, Gedeon Richter Plc, Budapest, Hungary. gy.szabo@richter.hu
Fischer
János
J
Kis-Varga
Agnes
A
Gyires
Klára
K
D019342:Acetic Acid; D000818:Animals; D002351:Carrageenan; D000068579:Celecoxib; D002908:Chronic Disease; D003460:Crystallization; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000737:chemistry; D013237:Stereoisomerism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D011994:Recombinant Proteins; D013449:Sulfonamides; D000431:Ethanol; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D000068579:Celecoxib; D019342:Acetic Acid