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
  • 1. Pfizer Global Research & Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. [email protected]
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.

Products