title: Synthesis of new 1-(4-methane(amino)sulfonylphenyl)-5-(4-substituted-aminomethylphenyl)-3-trifluoromethyl-1H-pyrazoles: a search for novel nitric oxide donor anti-inflammatory agents.
abstract: A group of 1-(4-methane(amino)sulfonylphenyl)-5-(4-substituted-aminomethylphenyl)-3-trifluoromethyl-1H-pyrazoles (12a-f) was synthesized and evaluated as anti-inflammatory agents. While all the compounds (20mg/kg) showed significant anti-inflammatory activity after 3h of inflammation induction (69-89%) as compared to celecoxib (80%), 1-(4-methanesulfonylphenyl)-5-(4-methylaminomethylphenyl)-3-trifluoromethyl-1H-pyrazole (12 a) was found to be the most effective one (89%). The synthesis of model hybrid nitric oxide donor N-diazen-1-ium-1,2-diolate derivatives of 1-(4-methanesulfonylphenyl)-5-(4-substituted-aminomethylphenyl)-3-trifluoromethyl-1H-pyrazoles (10a-f) requires further investigation since the reaction of N-(4-(1-(4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzyl)ethanamine (12 b) or 1-(4-(1-(4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)benzyl)piperazine (12c) with nitric oxide furnished N-nitroso derivatives (13 and 14), respectively, rather than the desired N-diazen-1-ium-1,2-diolate derivatives (10b and 10 c).
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt. Electronic address: khaled.ahmed@pharm.bsu.edu.eg.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: Pharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.
authors.forename: Abeer
authors.initials: A
authors.lastname: Moawad
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Knaus
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan / Q000008:administration & dosage / Q000633:toxicity; D000068579:Celecoxib; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D020030:Nitric Oxide Donors; D011720:Pyrazoles; D013449:Sulfonamides; D009569:Nitric Oxide; D002351:Carrageenan; D000068579:Celecoxib
keywords: Anti-inflammatory activity; Cyclooxygenase; Diazen-1-ium-1,2-diolate nitric oxide donors; Pyrazoles