Captopril analogues as metallo-β-lactamase inhibitors

A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure–activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid.

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