Abstract
Aim:
To design and synthesize a series of benzenesulfonamide derivatives, 4-[2-alkylthio-5(4)-(4-substitutedphenyl)imidazole-4(5)-yl]benzenesulfonamides(4a-4j), which are intended to act as cyclooxygenase-2 (COX-2) inhibitors with good COX-2 inhibitor activity, and which will exert anti-inflammatory activities in vivo.
Methods:
Benzenesulfonamide derivatives were designed and synthesized through multi-step chemical reactions. All the synthesized compounds were evaluated in an in vitro assay. The active compound 4a-4f was selected for further evaluation in a carrageenan-induced rat paw edema model.
Results:
Docking studies showed that compound 4 bind into the primary binding site of COX-2 with the sulfonamide SO2NH2 moiety interacting with the secondary pocket amino acid residues. In the in vitro assay, compound 4 inhibited COX-2 with an inhibition concentration IC50 value of 1.23-8 nmol/L, compared to celecoxib with IC50 value of 1.5 nmol/L. Compound 4b and 4c had good potency and selectivity in comparison to the celecoxib. In the in vivo model, compound 4a-4f exhibited a moderate potency to inhibit 50% carrageenan-induced paw edema with value of 1.58-4.3 mg/kg. In the latter experiment, compound 4c was the most active compound.
Conclusion:
The anti-inflammatory effects obtained for compound 4a–4j could be due to the presence of fluorine or hydrogen substituents in the para position of the phenyl ring of these compounds.
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This project was supported by grants from the research council of Tehran University of Medical Sciences and Iran Chapter of TWAS (The Developing World of Academy of Sciences), and INSF (Iran National Science Foundation).
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Salimi, M., Ghahremani, M., Naderi, N. et al. Design, synthesis and pharmacological evaluation of 4-[2-alkylthio-5(4)-(4-substitutedphenyl)imidazole-4(5)yl]benzenesulfonamides as selective COX-2 inhibitors. Acta Pharmacol Sin 28, 1254–1260 (2007). https://doi.org/10.1111/j.1745-7254.2007.00619.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00619.x
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