Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1365368 | Bioorganic & Medicinal Chemistry Letters | 2008 | 5 Pages |
Abstract
A series of β-sulfonamide piperidine hydroxamates were prepared and shown to be potent inhibitors of the human epidermal growth factor receptor-2 (HER-2) sheddase with excellent selectivity against MMP-1, −2, −3, and −9. This was achieved by exploiting subtle differences within the otherwise highly conserved S1′ binding pocket of the active sites within the metalloprotease family. In addition, it was discovered that the introduction of polarity to the P1 and P1′ groups reduced the projected human clearance.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
David M. Burns, Chunhong He, Yanlong Li, Peggy Scherle, Xiangdong Liu, Cindy A. Marando, Mayanne B. Covington, Gengjie Yang, Max Pan, Sharon Turner, Jordan S. Fridman, Gregory Hollis, Kris Vaddi, Swamy Yeleswaram, Robert Newton, Steve Friedman,