Tri- and tetrapeptide analogs of kinins as potential renal vasodilators

Tri- and tetrapeptide analogues were synthesized and evaluated as renal vasodilators. These peptides were prepared by standard coupling reactions, which also provided good yields with hindered alpha-methyl amino acid derivatives. Preliminary evidence of renal vasodilator activity was determined in a...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1984-03, Vol.27 (3), p.325-341
Main Authors: Pfeiffer, Francis R, Chambers, Pamela A, Hilbert, Eileen E, Woodward, Paul W, Ackerman, Dennis M
Format: Article
Language:English
Subjects:
Animals
Bradykinin - analogs & derivatives
Bradykinin - pharmacology
Dogs
kidney
Kidney - blood supply
kinins
Peptide Fragments - pharmacology
peptide synthesis
Regional Blood Flow - drug effects
Structure-Activity Relationship
Vascular Resistance - drug effects
Vasodilator Agents - chemical synthesis
Vasodilator Agents - pharmacology
vasodilators
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Summary:Tri- and tetrapeptide analogues were synthesized and evaluated as renal vasodilators. These peptides were prepared by standard coupling reactions, which also provided good yields with hindered alpha-methyl amino acid derivatives. Preliminary evidence of renal vasodilator activity was determined in anesthetized dogs by measuring the effects on renal blood flow and calculating the accompanying changes in renal vascular resistance. The most potent compounds contained, in their basic structure, the L-prolyl-DL-alpha-methylphenylalanyl-L-arginine and L-prolyl-DL-alpha-methylphenylalanylglycyl-L-proline arrays. Substitution on the N-terminal proline with 4-phenylbutyryl and 4-(4-hydroxyphenyl)butyryl side chains produced enhanced renal vasodilator activity and, in certain cases, selectivity for the renal vasculature.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00369a017