| Abstract
| - A series of cysteine (Cys) derivatives having an alkyl or arylalkyl moiety on the α-amino groupof the amino acid have been synthesized as a novel type of inhibitor for carboxypeptidase A.These compounds are readily prepared starting with Cys in an optically active form. Thestructure−activity relationship study revealed that the inhibitors prepared from d-Cys aremuch more potent than the corresponding inhibitors obtained from l-Cys, and the most potentinhibitor in the series, (S)-1j with a Ki value of 55 ± 4 nM, is obtained by introducing a phenethylmoiety on the amino group of d-Cys. In comparison, the most active inhibitor in the series of2-substituted 3-mercaptopropanoic acid is found to be 20, in which the phenyl ring is linked tothe mercaptocarboxylic acid at the α-position with a methylene unit. A proposal that accountsfor the different structural requirement for the maximum activity between the two series ofinhibitors is provided.
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