Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

@article{Savi2011OrallyAA,
  title={Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.},
  author={Chris De Savi and Andrew R Pape and Yvonne Sawyer and David Milne and Chris Davies and John G. Cumming and Attilla Ting and Scott G Lamont and Peter D Smith and Jonathon Tart and Ken R Page and Peter Lindsay Moore},
  journal={Bioorganic & medicinal chemistry letters},
  year={2011},
  volume={21 11},
  pages={3301-6}
}
A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This… CONTINUE READING

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