Design and synthesis of procollagen C-proteinase inhibitors

Non-peptidic inhibitors of procollagen C-proteinase (PCP) were designed from substrate leads. Compounds were optimized for potency and selectivity, with N-substituted aryl sulfonamide hydroxamates having the best combination of these properties. Compounds 89 and 60 have IC50 values of 10 and 80 nM, respectively, against PCP; excellent selectivity over MMP's 1, 2, and 9; and activity in cell-based collagen deposition assays. (C) 2012 Elsevier Ltd. All rights reserved.