Design, synthesis, and biological evaluation of substituted 3-alkylthio-4,5-diaryl-4H-1,2,4-triazoles as selective COX-2 inhibitors.
A new type of 4,5-diaryl-4H-1,2,4-triazole, possessing C-3 thio and alkylthio (SH, SMe or SEt) substituents, was designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti-inflammatory activity. The compound, 3-ethylthio-5-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)-4H-1,2,4-triazole (10d), exhibited a high in vitro selectivity (COX-1 IC50=20.5 nM; COX-2 IC50=1.8 nM; SI=11.39) relative to the reference drug celecoxib (COX-1 IC50=3.7 nM; COX-2 IC50=2.2 nM; SI=1.68) and also showed good anti-inflammatory activity compared to celecoxib in a carrageenan-induced rat paw edema assay.
Navidpour
Latifeh
L
Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran 14174, Iran.
Shafaroodi
Hamed
H
Abdi
Khosrou
K
Amini
Mohsen
M
Ghahremani
Mohammad H
MH
Dehpour
Ahmad Reza
AR
Shafiee
Abbas
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D051381:Rats; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D014230:Triazoles