Heterocycle-based MMP inhibitors with P2' substituents

Bioorganic & Medicinal Chemistry Letters
S PikulG E Mieling

Abstract

Potent and selective inhibition of matrix metalloproteinases was demonstrated for a series of sulfonamide-based hydroxamic acids. The design of the heterocyclic sulfonamides incorporates a six- or seven-member central ring with a P2' substituent that can be modified. Binding interactions of this substituent at the S2' site are believed to contribute to high inhibitory potency against stromelysin, collagenase-3 and gelatinases A and B, and to provide selectivity against collagenase-1 and matrilysin. An X-ray structure of a stromelysin inhibitor complex was obtained to provide insights into the SAR and selectivity trends observed for the series.

Citations

Dec 20, 2003·Bioorganic & Medicinal Chemistry Letters·Dawei MaQizhuang Ye
Apr 21, 2004·Journal of Molecular Biology·I BertiniB Terni
Dec 12, 2001·Bioorganic & Medicinal Chemistry Letters·Wenqing YaoCarl P Decicco
Oct 25, 2011·Journal of Medicinal Chemistry·Sérgio M MarquesM Amélia Santos
Aug 22, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Luis A AlcarazLeonardo Gonnelli
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Jul 27, 2001·Journal of Medicinal Chemistry·S PikulG E Mieling
Feb 6, 2007·Bioorganic & Medicinal Chemistry·Rajeshwar P Verma, Corwin Hansch

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