| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1370969 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
Abstract
A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure–activity and structure–property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Chris De Savi, Andrew Pape, Yvonne Sawyer, David Milne, Chris Davies, John G. Cumming, Attilla Ting, Scott Lamont, Peter D. Smith, Jonathon Tart, Ken Page, Peter Moore,