Design, Synthesis, and Biological Evaluation of Phenylamino-Substituted 6,11-Dihydro-dibenzo[b,e]oxepin-11-ones and Dibenzo[a,d]cycloheptan-5-ones:  Novel p38 MAP Kinase Inhibitors

The pathogenesis of chronic inflammatory diseases is promoted by various pro-inflammatory cytokines. p38 MAP kinase seems to be a valid target as it controls proinflammatory cytokine levels on both transcriptional and translational levels. Starting from benzophenone-type inhibitors, a rigidisation strategy lead to 3-amino-6,11-dihydro-dibenzo[b,e]thiepin-11-one, phenylamino-substituted 6,11-dihydro-dibenzo[b,e]oxepin-11-ones, and dibenzo[a,d]cyclohepten-5-ones. Synthesis, p38 inhibition, and CYP-inhibition of selected compounds are described.