Author/Authors :
Stanislaw Pikul، نويسنده , , Kelly McDow Dunham، نويسنده , , Neil G. Almstead، نويسنده , , Biswanath De، نويسنده , , Michael G. Natchus، نويسنده , , Yetunde O. Taiwo، نويسنده , , Lisa E. Williams، نويسنده , , Barbara A. Hynd، نويسنده , , Lily C. Hsieh، نويسنده , , Michael J. Janusz، نويسنده , , Fei Gu، نويسنده , , Glen E. Mieling، نويسنده ,
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.
