RESUMEN

A broad series of N-(3-mercaptoacyl) amino acid derivatives was evaluated for their ability to inhibit atriopeptidase (neutral endopeptidase, EC 3.4.24.11) in vitro and in vivo. Structural parameters studied were (i) the substituent on the 2-position of the 3-mercaptopropionyl moiety, (ii) the amino acid component, (iii) the S-terminal derivative, and (iv) the C-terminal derivative. Optimum activity was observed for derivatives of methionine and S-alkylcysteines. N-[3-Mercapto-2(S)-[(2-methylphenyl)methyl]-1-oxopropyl]-L-methionine was identified as a highly effective inhibitor of atriopeptidase meriting evaluation as a potential cardiovascular therapeutic agent.

Asunto(s)

Aminoácidos/farmacología , Antihipertensivos/farmacología , Cisteína/análogos & derivados , Metionina/química , Neprilisina/antagonistas & inhibidores , Secuencia de Aminoácidos , Aminoácidos/química , Animales , Factor Natriurético Atrial/farmacología , Inhibidores de la Colinesterasa/farmacología , Masculino , Datos de Secuencia Molecular , Ratas , Ratas Endogámicas SHR , Ratas Sprague-Dawley , Relación Estructura-Actividad