2. Academic Validation
  3. Pyran-containing sulfonamide hydroxamic acids: potent MMP inhibitors that spare MMP-1

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

  • Bioorg Med Chem Lett. 2004 Jul 5;14(13):3389-95. doi: 10.1016/j.bmcl.2004.04.083.
Lawrence A Reiter 1,  Ralph P Robinson,  Kim F McClure,  Christopher S Jones,  Matthew R Reese,  Peter G Mitchell,  Ivan G Otterness,  Marcia L Bliven,  Jennifer Liras,  Santo R Cortina,  Kathleen M Donahue,  James D Eskra,  Richard J Griffiths,  Mary E Lame,  Arturo Lopez-Anaya,  Gary J Martinelli,  Shunda M McGahee,  Sue A Yocum,  Lori L Lopresti-Morrow,  Lisa M Tobiassen,  Marcie L Vaughn-Bowser
Affiliations

Affiliation

  • 1 Pfizer Global Research & Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. reiterla@groton.pfizer.com
PMID: 15177439 DOI: 10.1016/j.bmcl.2004.04.083
Abstract

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.

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