Human neutrophil elastase (HNE), a 30 kDa serine protease located within the azurophil granules of neutrophils, shows high activity at inflammation sites associated with various inflammatory diseases and causes tissue destruction. As such, HNE is a potential target for the treatment of neutrophilic inflammatory diseases, including chronic obstructive pulmonary disease and anti-neutrophil cytoplasmic antibody associated vasculitis. In our search for a novel orally available non-peptide HNE inhibitor, we found 1-phenyl uracil derivatives as a lead compound. To improve these derivatives HNE inhibitory activity and ADME profiles, we modified the substituents at the R1-R4 positions and found DSP-1363 as a promising drug candidate. DSP-1363 showed good chemical stability, beneficial effects in a number of rat inflammation models, and good safety profiles in monkeys. In this presentation, we would like to report the details of our identification of DSP-1363 and highlight the pharmacological profiles of this drug candidate.

DSP-1363, a novel orally available human neutrophil elastase inhibitor for the treatment of inflammation

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.