Discovery of potent and selective succinyl hydroxamate inhibitors of matrix metalloprotease-3 (Stromelysin-1)

Structure–activity relationships are described for a series of succinyl hydroxamic acids 4a–o as potent and selective inhibitors of matrix metalloprotease-3 (stromelysin-1). Optimisation of P1′ and P3′ groups gave compound 4j (MMP-3 IC50=5.9 nM) which was >140-fold less potent against MMP-1 (IC50=51,000 nM), MMP-2 (IC50=1790 nM), MMP-9 (IC50=840 nM) and MMP-14 (IC50=1900 nM).