Abstract
We disclose further optimization of hydantoin TNF-α convertase enzyme (TACE) inhibitors. SAR with respect to the non-prime region of TACE active site was explored. A series of biaryl substituted hydantoin compounds was shown to have sub-nanomolar K i, good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.
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