A novel series of highly selective inhibitors of MMP-3

  • Bioorg Med Chem Lett. 2007 Dec 15;17(24):6750-3. doi: 10.1016/j.bmcl.2007.10.042.
Gavin A Whitlock  1 ,  Kevin N Dack ,  Roger P Dickinson ,  Mark L Lewis
Affiliations
  • 1. Sandwich Chemistry Department, Pfizer Global Research and Development, Sandwich Labs, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. [email protected]
PMID: 18029177 DOI: 10.1016/j.bmcl.2007.10.042
Abstract

The design and synthesis of a series of highly selective hydroxamate inhibitors of stromelysin-1 (MMP-3) is described. Substitution of a 4-biaryl piperidine sulfonamide core, which binds at the S1' subsite of MMP-3, was optimised to give potent inhibitors of MMP-3, with greater than 300-fold selectivity over MMP-1, MMP-2, MMP-9 and MMP-14. Compounds 26 and 27 were identified as having the best balance of pharmacology and properties required for topical drug delivery.

Products