Abstract
Simple synthesis of modafinil derivatives and their biological activity are described. The key synthetic strategies involve substitution and coupling reactions. We determined the anti-inflammatory effects of modafinil derivatives in cultured BV2 cells by measuring the inhibition of nitrite production and expression of iNOS and COX-2 after LPS stimulation. It was found that for sulfide analogues introduction of aliphatic groups on the amide part (compounds 11a–d) resulted in lower anti-inflammatory activity compared with cyclic or aromatic moieties (compounds 11e–k). However, for the sulfoxide analogues, introduction of aliphatic moieties (compounds 12a–d) showed higher anti-inflammatory activity than cyclic or aromatic fragments (compounds 12e–k) in BV-2 microglia cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Antioxidants / chemical synthesis
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Antioxidants / chemistry
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Antioxidants / pharmacology
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Benzhydryl Compounds* / chemistry
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Benzhydryl Compounds* / pharmacology
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Cell Line, Tumor
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Cell Survival / drug effects
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Cyclooxygenase 2 / metabolism*
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Humans
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Lipopolysaccharides / immunology
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Modafinil
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Nitric Oxide / metabolism
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Nitric Oxide Synthase Type II / metabolism*
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Nitrites / antagonists & inhibitors*
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Safrole / analogs & derivatives
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Safrole / chemistry
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Sulfides / chemistry
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antioxidants
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Benzhydryl Compounds
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Lipopolysaccharides
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Nitrites
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Sulfides
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Nitric Oxide
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Nitric Oxide Synthase Type II
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Cyclooxygenase 2
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Modafinil
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Safrole
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sulfoxide