Synthesis, Cyclooxygenase Inhibition, Anti-Inflammatory Evaluation, and Ulcerogenic Liability of New 1,3,5-Triarylpyrazoline Derivatives Possessing a Methanesulfonyl Pharmacophore.
A new series of 1,3,5-triarylpyrazolines 13a-l was synthesized and all prepared compounds were evaluated for their in vitro COX-1/COX-2 inhibitory activity and in vivo anti-inflammatory activity. All test compounds were more selective for the COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compound 13h was the most COX-2 selective compound (COX-2 selectivity index (SI) = 10.23) and the most potent anti-inflammatory derivative (ED50= 60.1 µmol/kg) in comparison with celecoxib (COX-2 SI = 9.29 and ED50= 81.4 µmol/kg). All screened compounds were less ulcerogenic (ulcer indexes (UI) = 0.33-1.33) than aspirin (UI = 2.33) and comparable to celecoxib (UI = 0.33).
Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef, Egypt. khaled.ahmed@pharm.bsu.edu.eg.
Khaled R A
KR
Abdellatif
Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef, Egypt.
Wael A A
WA
Fadaly
Faculty of Pharmacy, Department of Pharmacology and Toxicology, Beni-Suef University, Beni-Suef, Egypt.
Amany A
AA
Azouz
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000138:chemical synthesis* / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects; D000068579:Celecoxib / Q000009:adverse effects / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012756:Sheep; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014456:Ulcer / Q000139:chemically induced*
C000617414:5-(4-chlorophenyl)-1-(4-methanesulfonylphenyl)-3-thiophen-2-yl-4,5-dihydro-1H-pyrazole; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011720:Pyrazoles; D013876:Thiophenes; D000068579:Celecoxib; D001241:Aspirin
1,3,5-Triarylpyrazoline; Anti-inflammatory; Cyclooxygenase-2 inhibitors; Pyrazoline