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Potent and Selective Carboxylic Acid-Based Inhibitors of Matrix Metalloproteinases

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journal contribution
posted on 28.06.2001, 00:00 by Stanislaw Pikul, Norman E. Ohler, Greg Ciszewski, Michael C. Laufersweiler, Neil G. Almstead, Biswanath De, Michael G. Natchus, Lily C. Hsieh, Michael J. Janusz, Sean X. Peng, Todd M. Branch, Selane L. King, Yetunde O. Taiwo, Glen E. Mieling
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.