Potent, selective pyrimidinetrione-based inhibitors of MMP-13.

@article{Reiter2006PotentSP,
  title={Potent, selective pyrimidinetrione-based inhibitors of MMP-13.},
  author={Lawrence A. Reiter and Kevin Daniel Freeman-Cook and Christopher Stephen Jones and Gary J. Martinelli and Amy S Antipas and Martin A. Berliner and Kaushik Datta and James T. Downs and James D. Eskra and Michael D. Forman and Elaine M Greer and Roberto Guzm{\'a}n and Joel R. Hardink and Fouad Janat and Nandell F. Keene and Ellen R. Laird and Jennifer L. Liras and Lori L. Lopresti-Morrow and Peter G. Mitchell and Jayvardhan Pandit and Donald A. Robertson and Diana M. Sperger and Marcie L Vaughn-Bowser and Darra M Waller and Sue A. Yocum},
  journal={Bioorganic & medicinal chemistry letters},
  year={2006},
  volume={16 22},
  pages={
          5822-6
        }
}
Using SAR from two related series of pyrimidinetrione-based inhibitors, compounds with potent MMP-13 inhibition and >100-fold selectivity against other MMPs have been identified. Despite high molecular weights, clogPs, and polar surface areas, the compounds are generally well absorbed and have excellent pharmacokinetic (PK) properties when dosed as sodium salts. In a rat fibrosis model, a compound from the series displayed no fibrosis at exposures many fold greater than its MMP-13 IC50. 

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