Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13

KD Freeman-Cook, LA Reiter, MC Noe…

文献索引：Freeman-Cook, Kevin D.; Reiter, Lawrence A.; Noe, Mark C.; Antipas, Amy S.; Danley, Dennis E.; Datta, Kaushik; Downs, James T.; Eisenbeis, Shane; Eskra, James D.; Garmene, David J.; Greer, Elaine M.; Griffiths, Richard J.; Guzman, Roberto; Hardink, Joel R.; Janat, Fouad; Jones, Christopher S.; Martinelli, Gary J.; Mitchell, Peter G.; Laird, Ellen R.; Liras, Jennifer L.; Lopresti-Morrow, Lori L.; Pandit, Jayvardhan; Reilly, Usa D.; Robertson, Donald; Vaughn-Bowser, Marcie L.; Wolf-Gouviea, Lilli A.; Yocum, Sue A. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 23 p. 6529 - 6534

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被引用次数: 14

摘要

Explorations in the pyrimidinetrione series of MMP-13 inhibitors led to the discovery of a series of spiro-fused compounds that are potent and selective inhibitiors of MMP-13. While other spiro-fused motifs are hydrolytically unstable, presumably due to electronic destabilization of the pyrimidinetrione ring, the spiropyrrolidine series does not share this liability. Greater than 100-fold selectivity versus other MMP family members was achieved ...