title: Simple synthesis of modafinil derivatives and their anti-inflammatory activity.
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.
authors.affiliation: Department of Neuroscience and Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul 158-710, Korea.
authors.forename: Jae-Chul
authors.initials: JC
authors.lastname: Jung
authors.forename: Yeonju
authors.initials: Y
authors.lastname: Lee
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Son
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Lim
authors.forename: Mankil
authors.initials: M
authors.lastname: Jung
authors.forename: Seikwan
authors.initials: S
authors.lastname: Oh
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D000077408:Modafinil; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D009573:Nitrites / Q000037:antagonists & inhibitors*; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001559:Benzhydryl Compounds; D008070:Lipopolysaccharides; D009573:Nitrites; D013440:Sulfides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000077408:Modafinil; D012451:Safrole; C005746:sulfoxide