Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1376313 | Bioorganic & Medicinal Chemistry Letters | 2007 | 5 Pages |
Abstract
A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P3 which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Shaun R. Stauffer, Matthew G. Stanton, Alison R. Gregro, Melissa A. Steinbeiser, Jennifer R. Shaffer, Philippe G. Nantermet, James C. Barrow, Kenneth E. Rittle, Dennis Collusi, Amy S. Espeseth, Ming-Tain Lai, Beth L. Pietrak, M. Katharine Holloway,