Synthesis, SAR, and Biological Evaluation of α‐Sulfonylphosphonic Acids as Selective Matrix Metalloproteinase Inhibitors

Selective MMP inhibitors: Eleven α‐sulfonylphosphonates were synthesized and tested as MMP inhibitors. The IC50 values for most of them are in the nanomolar range against MMP‐2, ‐8, ‐13, and ‐14, with an interesting selectivity profile versus MMP‐9. magnified image Eleven simple α‐sulfonylphosphonates, new analogues of previously reported α‐sulfonylaminophosphonates, were prepared and tested as MMP inhibitors. The IC50 values of most of these compounds are in the nanomolar range against MMP‐2, ‐8, ‐13, and ‐14. Compound 11 proved to be the most effective inhibitor of MMP‐2 (IC50=60 nM), with interesting selectivity versus the antitarget enzymes MMP‐3 and MMP‐9. The mode of binding of the new phosphonates in the active site of MMP‐2 was studied, and variations in inhibition was explained by means of molecular modeling.