Structure-Activity Relationships of 6-Nitroquinazolines: Dual-Acting Compounds with Inhibitory Activities toward both TNF-α Production and T Cell Proliferation

摘要

We synthesized various 6-nitroquinazolines by modifying the structure of compound 1 and evaluated their inhibitory activities toward both TNF-α production and T cell proliferation responses. The presence of the unsubstituted piperazine ring at the C(7)-position was required for both inhibitory activities. In this series of compounds, 5d and 5f, containing the 4-fluorophenyl and 3,4-difluorophenyl moiety, respectively, at the C(4)-position, showed the suppressing effects toward both responses with low cell growth inhibition. Furthermore, the oral administration of these compounds mentioned above at doses of 30 and 100 mg/kg also resulted in significant inhibition of TNF-α production induced by LPS in vivo.