Simple Synthesis of Modafinil Derivatives and Their Anti-inflammatory Activity

• Main Authors: Mankil Jung, Seikwan Oh, Eunyoung Lim, Jee-Young Son, Yeonju Lee, Jae-Chul Jung
• Format: Article
• Language: English
• Published: MDPI AG 2012-09-01
• Series: Molecules
• Subjects: modafinil; anti-inflammation; nitric oxide; <em>S</em>-alkylation; coupling reaction
• Online Access: http://www.mdpi.com/1420-3049/17/9/10446

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 <strong>11a</strong>–<strong>d</strong>) resulted in lower anti-inflammatory activity compared with cyclic or aromatic moieties (compounds <strong>1</strong><strong>1e</strong>–<strong>k</strong>). However, for the sulfoxide analogues, introduction of aliphatic moieties (compounds <strong>1</strong><strong>2a</strong>–<strong>d</strong>) showed higher anti-inflammatory activity than cyclic or aromatic fragments (compounds <strong>1</strong><strong>2e</strong>–<strong>k</strong>) in BV-2 microglia cells.