Synthesis and biological evaluation of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides: A class of potent aggrecanase-1 inhibitors

The prevention of aggrecan (a key component of cartilage) cleavage via the inhibition of aggrecanase-1 may provide a unique opportunity to stop the progression of cartilage degradation in osteoarthritis. The evaluation of a series of biphenylsulfonamides resulted in the identification of the ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides analogs (19–21 and 24) with improved Agg-1 inhibition and MMP-2, MMP-13 activity.

Graphical abstractA subset of ((4-keto)-phenoxy)methyl biphenyl-4-sulfonamides were identified as potent Agg-1, MMP-2 and MMP-13 inhibitors through the synthesis of a series of (Phenoxy)methyl biphenylsulfonamide carboxylates.Figure optionsDownload full-size imageDownload as PowerPoint slide