Pyran-containing sulfonamide hydroxamic acids: potent MMP inhibitors that spare MMP-1

Graphic The SAR of a series of sterically hindered sulfonamide hydroxamic acids with relatively large P 1′ groups is described. The compounds typically spare MMP-1 while being potent inhibitors of MMP-13. The metabolically more stable compounds in the series contain either a monocyclic or bicyclic p...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2004-07, Vol.14 (13), p.3389-3395
Hauptverfasser: Reiter, Lawrence A., Robinson, Ralph P., McClure, Kim F., Jones, Christopher S., Reese, Matthew R., Mitchell, Peter G., Otterness, Ivan G., Bliven, Marcia L., Liras, Jennifer, Cortina, Santo R., Donahue, Kathleen M., Eskra, James D., Griffiths, Richard J., Lame, Mary E., Lopez-Anaya, Arturo, Martinelli, Gary J., McGahee, Shunda M., Yocum, Sue A., Lopresti-Morrow, Lori L., Tobiassen, Lisa M., Vaughn-Bowser, Marcie L.
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Sprache:eng
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Zusammenfassung:Graphic The SAR of a series of sterically hindered sulfonamide hydroxamic acids with relatively large P 1′ groups is described. The compounds typically spare MMP-1 while being potent inhibitors of MMP-13. The metabolically more stable compounds in the series contain either a monocyclic or bicyclic pyran ring adjacent to the hydroxamate group. Despite the sparing of MMP-1, pre-clinical and clinical studies revealed that fibrosis in rats and MSS in humans is still produced.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2004.04.083