A novel series of carboxylic acids containing a substituted piperidine were synthesized and tested for inhibition of selected matrix metalloproteinases. Multiple analogues prepared based on this novel design were found to inhibit the target MMPs (MMP-2, -3, -8, -9, and -13) with unprecedented, low nanomolar potency while, at the same time, sparing MMP-1 and MMP-7. Solubility and plasma protein binding of several members of this new series of carboxylic acids were also investigated.
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Pikul et al. (2001) studied this question.
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