Synthesis of novel 1,3,4-trisubstituted pyrazoles as anti-inflammatory and analgesic agents

• Published in: European journal of medicinal chemistry 2013-05, Vol.63, p.645-654
• Main Authors: Ragab, Fatma A., Abdel Gawad, Nagwa M., Georgey, Hanan H., Said, Mona F.
• Format: Article
• Language: English
• Subjects: Analgesic; Analgesics - chemical synthesis; Analgesics - chemistry; Analgesics - pharmacology; Animals; Anti-inflammatory; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Benzoquinones; Carrageenan; COX inhibition; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - chemical synthesis; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - pharmacology; Edema - chemically induced; Edema - prevention & control; Male; Mice; Models, Chemical; Molecular Structure; Pain - chemically induced; Pain - prevention & control; Pyrazole; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Pyrazoles - pharmacology; Pyrrole; Rats; Rats, Wistar; Schiff's base; Structure-Activity Relationship
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2013.03.005

Some novel 1,3,4-trisubstituted pyrazoles were synthesized and screened for their anti-inflammatory and analgesic activities as well as their ulcerogenic liability. They showed anti-inflammatory and analgesic activities with better GIT tolerance than the standard drug phenylbutazone. In addition, IC50 values for 5e and 8e were recorded. Compound 5e was found to be the most active one as anti-inflammatory and analgesic agent. On the other hand, COX-1/COX-2 isozyme selectivity was also done which showed equal inhibition to both isoforms. [Display omitted] The manuscript deals with synthesis of 1,3,4-trisubstituted pyrazoles derivatives. Anti-inflammatory, analgesic activities and ulcerogenic effect were evaluated. COX-1/COX-2 isozyme selectivity was also evaluated for selected better active compounds. ► Series novel 1,3,4-trisubstituted pyrazoles derivatives were prepared. ► Anti-inflammatory activity, analgesic activities were performed. ► Ulcerogenic effect showed better GIT tolerance than phenylbutazone. ► COX-1/COX-2 isozyme selectivity was done and showed equal inhibition to both isoforms. ► Compounds 5e, 5f and 8e showed appreciable activity.