Biaryl substituted hydantoin compounds as TACE inhibitors

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 Ki, good rat PK, and good selectivity versus MMP-1, -2, -3, -7, -9, and -13.

Graphical abstractA series of biaryl substituted hydantoin TACE inhibitors is disclosed. Many compounds in this series exhibit sub-nanomolar TACE activities and good rat PK.Figure optionsDownload full-size imageDownload as PowerPoint slide