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Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors
L H Foley1, R Palermo, P Dunten
1Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. louise.foley@roche.com
Bioorganic & Medicinal Chemistry Letters
|May 1, 2001
Abstract:
The 5,5-disubstitutedpyrimidine-2,4,6-triones represent a new class of MMP inhibitors showing selectivity for the gelatinases A and B, collagenase-3, and human neutrophil collagenase. The SAR presented here is in good agreement with an X-ray structure of compound 5 bound to the catalytic domain of stromelysin-1. While of the barbiturate structural class, compound 5 did not show any toxic or sedative effects.