simple synthesis of modafinil derivatives and their anti-inflammatory activity简单莫达非尼衍生物的合成及其抗炎活性.pdf

Molecules 2012, 17, 10446-10458; doi:10.3390/molecules170910446 OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Simple Synthesis of Modafinil Derivatives and Their Anti-inflammatory Activity 1 1 2 2 2 Jae-Chul Jung , Yeonju Lee , Jee-Young Son , Eunyoung Lim , Mankil Jung and Seikwan Oh 1,* 1 Department of Neuroscience and Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Seoul 158-710, Korea 2 Department of Chemistry, Yonsei University, Seoul 120-749, Korea * Author to whom correspondence should be addressed; E-Mail: skoh@ewha.ac.kr. Received: 2 July 2012; in revised form: 10 August 2012 / Accepted: 14 August 2012 / Published: 3 September 2012 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 (compou