The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis

…, S Lamont, D Milne, C Cook, P Moore, Y Sawyer…

Index: De Savi, Chris; Pape, Andrew; Cumming, John G.; Ting, Attilla; Smith, Peter D.; Burrows, Jeremy N.; Mills, Mark; Davies, Chris; Lamont, Scott; Milne, David; Cook, Calum; Moore, Peter; Sawyer, Yvonne; Gerhardt, Stefan Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 5 p. 1376 - 1381

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Citation Number: 14

Abstract

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM- TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure–activity relationships, and ...