Hydantoin based inhibitors of MMP13--discovery of AZD6605.
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De Savi C, Waterson D, Pape A, Lamont S, Hadley E, Mills M, Page KM, Bowyer J, Maciewicz RA
Hydantoin based inhibitors of MMP13--discovery of AZD6605.
Bioorg Med Chem Lett. 2013 Aug 15;23(16):4705-12. doi: 10.1016/j.bmcl.2013.05.089. Epub 2013 Jun 10.
- PubMed ID
- 23810497 [ View in PubMed]
- 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.