The design and synthesis of novel orally active inhibitors of AP-1 and NF-κB mediated transcriptional activation. SAR of In vitro and In vivo studies

Abstract We have developed novel orally active quinazoline analogues as inhibitors of AP-1 and NF-κB mediated transcriptional activation. Among the derivatives prepared, 1-[2-(2-thienyl)quinazolin-4-ylamino]-3-methyl-3-pyrroline-2,5-dione ( 10 ) showed significant activity in an adjuvant-induced arthritis rat model by reducing the swelling by 65% in the non-injected foot. The synthesis, structure–activity relationship, and in vivo activity are described.