Synthesis and sar studies for the inhibition of tnf-α production. part 2. 2-[3-(cyclopentyloxy)-4-methoxyphenyl]-substituted-1 -isoindolinone derivatives.

This study describes the synthesis andin vitro evaluation of 2-[3-(cyclopentyloxy)-4-methox-yphenyl]-1-isoindolinone derivatives substituted on benzene moiety of isoindoline ring for the inhibition of TNF-α production. From this study, we have found the 6-C position on isoindolinone ring is an optimal derivatization site. Among the compounds synthesized, 6-amino-2-[3-(cyclopentyloxy)-4-methoxyphenyl]-1 -isoindolinone (6) was the most potent in inhibitory activity of TNF-α production in LPS-stimulated RAW264.7 cells.