Design, synthesis and in vivo anti-inflammatory activities of 2,4-diaryl-5-4H-imidazolone derivatives.
A series of 2,4-diaryl-5(4H)-imidazolones were prepared and evaluated for their anti-inflammatory activities. Some selected 2,4-diaryl-5(4H)-imidazolones exhibited excellent anti-inflammatory activity in the carrageenan-induced rat paw edema model. Structure Activity Relationships within the series were studied. The substitution at the N-sulfonamide moiety by a small hydrophilic acetyl group resulted in compounds with superior in vivo anti-inflammatory properties. As expected from their COX-2 selectivity, most of the active compounds lacked gastrointestinal toxicity in vivo in rats after a 3-day treatment of 25 mg/kg/day.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Helwan University, Cairo 11790, Egypt.
Moustafa
M
El-Araby
Abdelsattar
A
Omar
Hassanein H
HH
Hassanein
Abdel-Ghany H
AG
El-Helby
Asharf A
AA
Abdel-Rahman
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D051546:Cyclooxygenase 2 / Q000737:chemistry; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D062105:Molecular Docking Simulation; D011485:Protein Binding; D051381:Rats; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D007093:Imidazoles; C117197:imidazolone; D051546:Cyclooxygenase 2