2. Academic Validation
  3. The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis

The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis

  • Bioorg Med Chem Lett. 2011 Mar 1;21(5):1376-81. doi: 10.1016/j.bmcl.2011.01.036.
Chris De Savi 1,  Andrew Pape,  John G Cumming,  Attilla Ting,  Peter D Smith,  Jeremy N Burrows,  Mark Mills,  Chris Davies,  Scott Lamont,  David Milne,  Calum Cook,  Peter Moore,  Yvonne Sawyer,  Stefan Gerhardt
Affiliations

Affiliation

  • 1 Respiratory and Inflammation Research Area, AstraZeneca, Alderley Park, Macclesfield, Cheshire, UK. chris.desavi2@astrazeneca.com
PMID: 21300546 DOI: 10.1016/j.bmcl.2011.01.036
Abstract

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described.

Figures
Products