Mercaptoacyl aminoacid inhibitors of atriopeptidase. 1. Structure-activity relationship studies of methionine and S-alkylcysteine derivatives
| Autor: | Edmund J. Sybertz, Robert W. Watkins, Bernard R. Neustadt, Caroline Foster, Alan Bronnenkant, Elizabeth M. Smith, Martin F. Haslanger, T. Nechuta |
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| Rok vydání: | 1994 |
| Předmět: |
Male
Stereochemistry Molecular Sequence Data Substituent Rats Sprague-Dawley Structure-Activity Relationship chemistry.chemical_compound Methionine Rats Inbred SHR Drug Discovery Animals Structure–activity relationship Moiety Amino Acid Sequence Cysteine Amino Acids Antihypertensive Agents chemistry.chemical_classification biology Chemistry Absolute configuration Rats Amino acid Enzyme Enzyme inhibitor biology.protein Molecular Medicine Neprilysin Cholinesterase Inhibitors Atrial Natriuretic Factor |
| Zdroj: | Journal of Medicinal Chemistry. 37:2461-2476 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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