Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1372318 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
Abstract
Piperidine ether and aryl piperazine hydantoins are reported as potent inhibitors of MMP13. A medicinal chemistry campaign focused on replacing the reverse hydroxamate zinc binding group associated with historical inhibitors with a hydantoin zinc binding group then optimising MMP13 potency, solubility and DMPK properties whilst maintaining good selectivity over MMP14. A number of high quality candidates were progressed and following rat and dog safety evaluation, AZD6605 (3m) was identified as a candidate drug.
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Related Topics
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Chemistry
Organic Chemistry
Authors
Chris De Savi, David Waterson, Andrew Pape, Scott Lamont, Elma Hadley, Mark Mills, Ken M. Page, Jonathan Bowyer, Rose A. Maciewicz,