Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10593386 | Bioorganic & Medicinal Chemistry Letters | 2013 | 7 Pages |
Abstract
This Letter describes the discovery of GSK189254 and GSK239512 that were progressed as clinical candidates to explore the potential of H3 receptor antagonists as novel therapies for the treatment of Alzheimer's disease and other dementias. By carefully controlling the physicochemical properties of the benzazepine series and through the implementation of an aggressive and innovative screening strategy that employed high throughput in vivo assays to efficiently triage compounds, the medicinal chemistry effort was able to rapidly progress the benzazepine class of H3 antagonists through to the identification of clinical candidates with robust in vivo efficacy and excellent developability properties.
Keywords
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
David M. Wilson, James Apps, Nicholas Bailey, Mark J. Bamford, Isabel J. Beresford, Kim Brackenborough, Michael A. Briggs, Stephen Brough, Andrew R. Calver, Barry Crook, Rebecca K. Davis, Robert P. Davis, Susannah Davis, David K. Dean, Leanne Harris,