| Literature DB >> 16942871 |
Lawrence A Reiter1, 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, Nandell F Keene, Ellen R Laird, Jennifer L Liras, Lori L Lopresti-Morrow, Peter G Mitchell, Jayvardhan Pandit, Donald Robertson, Diana Sperger, Marcie L Vaughn-Bowser, Darra M Waller, Sue A Yocum.
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, 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.Entities:
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Year: 2006 PMID： 16942871 DOI： 10.1016/j.bmcl.2006.08.066
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823