The design, synthesis and structure–activity relationship (SAR) of a series of nonpeptidic 2- arylsulfonyl-1, 2, 3, 4-tetrahydro-isoquinoline-3-carboxylates and-hydroxamates as inhibitors of the matrix metalloproteinase human neutrophil collagenase (MMP-8) is described here. Based on available X-ray structures of MMP-8/inhibitor complexes, our structure-based design strategy was directed to complement major protein-ligand interaction regions ...