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Bioorg Med Chem Lett. 2011 Mar 1;21(5):1376-81. doi: 10.1016/j.bmcl.2011.01.036. Epub 2011 Jan 18.

The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.

Author information

1
Respiratory and Inflammation Research Area, AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK. chris.desavi2@astrazeneca.com

Abstract

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described.

PMID:
21300546
DOI:
10.1016/j.bmcl.2011.01.036
[Indexed for MEDLINE]

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