Myeloperoxidase (MPO) activity and subsequent generation of hypochlorous acid has been associated with the killing of host-invading microorganisms (e.g., bacteria, viruses, and fungi). However, during oxidative stress high plasma activity of secreted MPO can cause host tissue damage. As such, MPO levels and activity have been linked to several chronic inflammatory diseases. Herein we describe the discovery of a novel indole pharmacophore series, originating from an HTS hit. The indoles are mechanism-based irreversible inhibitors, and have been optimized for potency, <i>in vitro</i> safety selectivity, and oral exposure.

Novel indole pharmacophore series of irreversible MPO inhibitors

254th National Meeting (2017)

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