Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 20, Issue 17, Pages 5286-5289Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2010.06.134
Keywords
TACE; TNF-alpha convertase; TACE inhibitor; Hydantoin; Hydantoin zinc ligand; Anti-TNF; Rheumatoid arthritis
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We disclose further optimization of hydantoin TNF-alpha 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. (C) 2010 Published by Elsevier Ltd.
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