Application of spontaneous Schiff base copper chelates formation process to the design of a trypsin inhibitor

Salicylaldehyde derivatives carrying an amidinium group react spontaneously with alpha-amino acids in copper-containing aqueous media to afford very stable Schiff base copper chelates. A variety of Schiff base chelates were prepared from various alpha-amino acids. Each alpha-amino acid provides enantiomeric isomers due to the asymmetric alpha-carbon, except for glycine. Inhibitory activity of these amidinium chelates toward trypsin was generally very strong. Thus these compounds represent a novel series of potent trypsin inhibitors. The structure-activity relationship of the inhibitors is discussed based on their inhibition constants, though the variations are not large.