Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1361300 | Bioorganic & Medicinal Chemistry Letters | 2012 | 6 Pages |
Abstract
We report the discovery and optimization of a novel series of dihydrobenzofuran amides as γ-secretase modulators (GSMs). Strategies for aligning in vitro potency with drug-like physicochemical properties and good microsomal stability while avoiding P-gp mediated efflux are discussed. Lead compounds such as 35 and 43 have moderate to good in vitro potency and excellent selectivity against Notch. Good oral bioavailability was achieved as well as robust brain Aβ42 lowering activity at 100 mg/kg po dose.
Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Martin Pettersson, Douglas S. Johnson, Chakrapani Subramanyam, Kelly R. Bales, Christopher W. am Ende, Benjamin A. Fish, Michael E. Green, Gregory W. Kauffman, Ricardo Lira, Patrick B. Mullins, Thayalan Navaratnam, Subas M. Sakya, Cory M. Stiff,