Mercaptoacyl amino acid inhibitors of atriopeptidase. 1. Structure-activity relationship studies of methionine and S-alkylcysteine derivatives

  • J Med Chem. 1994 Jul 22;37(15):2461-76. doi: 10.1021/jm00041a026.
B R Neustadt  1 ,  E M Smith ,  T L Nechuta ,  A A Bronnenkant ,  M F Haslanger ,  R W Watkins ,  C J Foster ,  E J Sybertz
Affiliations
  • 1. Schering-Plough Research Institute, Kenilworth, New Jersey 07033-0539.
PMID: 8057292 DOI: 10.1021/jm00041a026
Abstract

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.

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