Potent and Selective Carboxylic Acid-Based Inhibitors of Matrix Metalloproteinases

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• 作者：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
• 刊名：Journal of Medicinal Chemistry
• 出版年：2001
• 出版时间：August 2, 2001
• 年：2001
• 卷：44
• 期：16
• 页码：2499 - 2502
• 全文大小：54K
• 年卷期：v.44,no.16(August 2, 2001)
• ISSN：1520-4804

文摘

A novel series of carboxylic acids containing asubstituted piperidine were synthesized and tested for inhibition of selected matrix metalloproteinases. Multiple analoguesprepared based on this novel design were found to inhibit thetarget MMPs (MMP-2, -3, -8, -9, and -13) with unprecedented,low nanomolar potency while, at the same time, sparingMMP-1 and MMP-7. Solubility and plasma protein binding ofseveral members of this new series of carboxylic acids werealso investigated.