Arylsulphonamide hydroxamic acids as potent inhibitors of MMP-13

Abstract

Pfizer has disclosed a series of phenoxyphenyl sulphonamide hydroxamic acids, containing Cα gem-disubstitution and a novel N-ethylcarboxylate moiety, which are potent inhibitors of matrix metalloproteinase-13 (MMP-13), an enzyme which has been implicated in such disease states as cancer and arthritis. The compounds are significantly selective (300-1000 fold) for MMP-13 versus MMP-1, the inhibition of which is believed to be associated with clinical side effects with previous broad spectrum MMP inhibitors. The Pfizer compounds are equally or more selective than several current clinical candidates and may have favourable pharmacodynamic profiles.

• arthritis
• cancer
• matrix metalloproteinase-13 (MMP-13)
• matrix metalloproteinase inhibitors