Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14.

@article{Blagg2005PotentPI,
  title={Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14.},
  author={Julian A Blagg and Mark C. Noe and Lilli A Wolf-Gouveia and Lawrence Reiter and Ellen R. Laird and Shang-Poa P Chang and Dennis E. Danley and James T Downs and Nancy C Elliott and James D. Eskra and Richard J. Griffiths and Joel R. Hardink and Amber I Haugeto and Christopher S Jones and Jennifer L. Liras and Lori L Lopresti-Morrow and Peter G. Mitchell and Jayvardhan Pandit and Ralph P Robinson and Chakrapani Subramanyam and Marcie L Vaughn-Bowser and Sue A. Yocum},
  journal={Bioorganic & medicinal chemistry letters},
  year={2005},
  volume={15 7},
  pages={1807-10}
}
Through the use of computational modeling, a series of pyrimidinetrione-based inhibitors of MMP-13 was designed based on a lead inhibitor identified through file screening. Incorporation of a biaryl ether moiety at the C-5 position of the pyrimidinetrione ring resulted in a dramatic enhancement of MMP-13 potency. Protein crystallography revealed that this… CONTINUE READING