Protease inhibitors: synthesis of Clostridium histolyticum collagenase inhibitors incorporating sulfonyl- -alanine hydroxamate moieties

A series of hydroxamates was obtained by the reaction of N-(4-nitrobenzyl)- -alanine with alkyl/arylsulfonyl halides, followed by conversion of the COOH group into CONHOH. Structurally-related compounds were prepared similarly by using arylsulfonyl isocyanates, aryl isocyanates or arylsulfenyl halides instead of the sulfonyl halides. Many of the new compounds showed nanomolar affinity for the bacterial collagenase isolated from the pathogen Clostridium histolyticum.