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In Vitro and In Vivo Models to Study Corneal Endothelial-mesenchymal Transition
Published on: August 20, 2016
Hydantoin based inhibitors of MMP13--discovery of AZD6605
Chris De Savi1, David Waterson, Andrew Pape
1Oncology Innovative Medicines, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, MA 02451, USA. chris.desavi2@astrazeneca.com
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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