Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and ulcerogenic liability of novel triarylpyrazoline derivatives as selective COX-2 inhibitors

• Published in: Bioorganic & medicinal chemistry letters 2015-12, Vol.25 (24), p.5787-5791
• Main Authors: Abdellatif, Khaled R.A., Abdelgawad, Mohamed A., Labib, Madlen B., Zidan, Taha H.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - therapeutic use; Celecoxib - pharmacology; Cyclooxygenase 1 - chemistry; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - chemistry; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemical synthesis; Cyclooxygenase 2 Inhibitors - metabolism; Cyclooxygenase 2 Inhibitors - therapeutic use; Cyclooxygenase-2 inhibitors; Edema - chemically induced; Edema - drug therapy; Edema - pathology; Inhibitory Concentration 50; Protein Binding; Pyrazoles - chemistry; Pyrazoles - metabolism; Pyrazoles - therapeutic use; Pyrazoline; Rats; Structure-Activity Relationship; Ulcer - pathology; Ulcer - prevention & control
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2015.10.047

[Display omitted] A new series of triarylpyrazoline derivatives 8a–p containing the most important COX-2 pharmacophore (SO2CH3 or/and SO2NH2) were synthesized by reaction of propen-1-one derivatives 6a–h with different phenyl hydrazine hydrochloride derivatives 7a–b in aqueous ethanol. All prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. All compounds were more selective for COX-2 isozyme than COX-1 isozyme and showed good in vivo anti-inflammatory activity. Compounds 8g, 8j and 8o showed the highest anti-inflammatory activity and were less ulcerogenic (Ulcer Index=6.85, 7.7, 5.92, respectively) than indomethacin (Ulcer Index=12.3) and comparable to celecoxib (Ulcer Index=4.85).