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 <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.

Keywords

• modafinil
• anti-inflammation
• nitric oxide
• &lt;em&gt;S&lt;/em&gt;-alkylation
• coupling reaction