Abstract
A new type of 1-aryl-5-(4-methylsulfonylphenyl)imidazoles, possessing C-2 alkylthio (SMe or SEt) substituents, were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors with in vivo anti-inflammatory activity. The compound, 1-(4-bromophenyl)-5-(4-methylsulfonylphenyl)-2-methylthioimidazole (11g), was the most potent and selective COX-2 inhibitor (COX-2 IC50=0.43 microM with no inhibition of COX-1 up to 25 microM) relative to the reference drug celecoxib (COX-2 IC50=0.21 microM with no inhibition of COX-1 up to 25 microM) and also showed very good anti-inflammatory activity compared to celecoxib in carrageenan-induced rat paw edema assay.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / chemistry*
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cyclooxygenase 2 / drug effects*
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Cyclooxygenase Inhibitors / chemical synthesis
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Cyclooxygenase Inhibitors / chemistry*
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Cyclooxygenase Inhibitors / pharmacology*
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Drug Design
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Drug Evaluation, Preclinical
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Imidazoles / chemical synthesis
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Imidazoles / chemistry*
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Imidazoles / pharmacology*
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Magnetic Resonance Spectroscopy
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Male
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Mass Spectrometry
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Models, Molecular
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Rats
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Rats, Sprague-Dawley
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Spectrophotometry, Infrared
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase Inhibitors
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Imidazoles
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Cyclooxygenase 2