A novel structural class of potent inhibitors of NF-κB activation:: Structure-activity relationships and biological effects of 6-aminoquinazoline derivatives

In this study, we have investigated the roles of substituents on the terminal phenyl ring at the C(4)-position of the quinazoline core to complete the structure-activity relationships (SARs) of our NF-kappaB activation inhibitors. Among them, compound 12j afforded highly potent inhibitory activity toward NF-kappaB transcriptional activation with IC50 value of 2nM, along with an excellent in vivo efficacy by reducing the edema formation seen in carrageenin-induced inflammation of the rat hind paw. (C) 2003 Elsevier Ltd. All rights reserved.