Novel 5,5-disubstitutedpyrimidine-2,4,6-trione as selective MMP inhibitors

The 5.5-disubstitutedpyrimidine-2,4.6-trione represent a new class of MIL IP 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. (C) 2001 Elsevier Science Ltd. All rights reserved.