Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1367320 | Bioorganic & Medicinal Chemistry Letters | 2006 | 5 Pages |
Abstract
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, c log Ps, 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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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Lawrence A. Reiter, Kevin D. Freeman-Cook, Christopher S. Jones, Gary J. Martinelli, Amy S. Antipas, Martin A. Berliner, Kaushik Datta, James T. Downs, James D. Eskra, Michael D. Forman, Elaine M. Greer, Roberto Guzman, Joel R. Hardink, Fouad Janat,