Discovery of novel spirocyclopropyl hydroxamate and carboxylate compounds as TACE inhibitors.


We have discovered nanomolar inhibitors of TNF-alpha convertase (TACE) comprised of a novel spirocyclic scaffold and either a carboxylate or hydroxamate zinc binding moiety. X-ray crystal structures and computer models of selected compounds binding to TACE explain the observed SAR. We report the first TACE X-ray crystal structure for an inhibitor with a… (More)
DOI: 10.1016/j.bmcl.2008.11.034


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