Design of inhibitors for trypsin and trypsin-like enzymes carrying Schiff base copper chelate moiety.

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Studies on trypsin-specific compounds can aid the design of clinically useful compounds, since a variety of physiologically important enzymes have trypsin-like specificity. We are also interested in the formation of very stable chelates from alpha-amino acid, salicylaldehyde and copper ion. In this regards we studied an application of the chelate formation process to the preparation of a variety of trypsin inhibitors.It was shown that salicylaldehyde derivatives carrying an amidinium group react spontaneously with alpha-amino acids to afford stable chelates. A wide variety of chelates compounds were successfully prepared. Inhibitory activity of these amidinium chelates toward trypsin was shown to be very strong. Some compounds synthesized in this work have been shown to be the strongest synthetic inhibitor ever known. It can be concluded that the series of compounds is informative for the elucidation of structure-activity relationship of trypsin inhibitors and for the design of clinically useful compounds. The results of the present work have been and will be published in three papers.