Design, synthesis and SAR of phenylamino-substituted 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones and 11H-dibenzo[b,f]oxepin-10-ones as p38 MAP kinase inhibitors

The p38 MAP kinase is a key enzyme in inflammatory diseases as it is involved in the biosynthesis of proinflammatory cytokines such as TNF-α and IL-1β. Small molecule p38 inhibitors suppress the production of these cytokines and therefore p38 is a promising drug target for novel anti-inflammatory therapeutics. In this study, we report the design, synthesis, and SAR of novel N-substituted 11H-dibenzo[b,f]oxepin-10-ones and 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones as p38 inhibitors.

Graphical abstractp38 MAP Kinase is an attractive and promising drug target for novel anti-inflammatory therapeutics. In this paper we present a novel, efficient synthesis route to obtain chloro-substituted 5,11-dihydro-dibenzo[a,d]cyclohepten-10-ones. Investigations of the inhibitory activities and structure–activity relationship of tricyclic inhibitors for p38 MAP kinase were accomplished.Figure optionsDownload full-size imageDownload as PowerPoint slide