A novel series of carboxylic acids containing a substituted piperidine were
synthesized and tested for inhibition of selected matrix metalloproteinase
s. Multiple analogues prepared based on this novel design were found to inh
ibit the target MMPs (MMP-2, -3, -8, -9, and -13) with unprecedented, low n
anomolar potency while, at the same time, sparing MMP-1 and MMP-7. Solubili
ty and plasma protein binding of several members of this new series of carb
oxylic acids were also investigated.