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

A series of novel MMP-13 and TNF-α 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 nitrogen and the P-1′ benzyloxy tailpiece is discussed. Moderate in vivo activity is observed with several members of this group. A series of novel piperazine-based hydroxamic acids with potent TACE activity is described.