Synthesis and biological activity of piperazine-based dual MMP-13 and TNF-α converting enzyme inhibitors

A series of novel MMP-13 and TNF-alpha converting enzyme inhibitors based on piperazine 2-hydroxamic acid scaffolds are described. The TACE, MMP-1 and MMP-13 activity of these inhibitors as well as the effect of substitution of the piperazine nitro-en and the P-1' benzyloxy tailpiece is discussed. Moderate in vivo activity is observed with several members of this group. (C) 2003 Elsevier Ltd. All rights reserved.