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

  title={Pyran-containing sulfonamide hydroxamic acids: potent MMP inhibitors that spare MMP-1.},
  author={Lawrence Reiter and Ralph P Robinson and Kim F McClure and Christopher S Jones and Matthew R Reese and Peter G. Mitchell and Ivan G. Otterness and Marcia L. Bliven and Jennifer L. Liras and Santo R Cortina and Kathleen M. Donahue and James D. Eskra and Richard J. Griffiths and Mary E. Lame and Arturo Lopez-Anaya and Gary J Martinelli and Shunda M McGahee and Sue A. Yocum and Lori L Lopresti-Morrow and Lisa M Tobiassen and Marcie L Vaughn-Bowser},
  journal={Bioorganic & medicinal chemistry letters},
  volume={14 13},
The SAR of a series of sterically hindered sulfonamide hydroxamic acids with relatively large P1' 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.