Tri- and tetrapeptide analogues 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 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.
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004285:Dogs; D007668:Kidney / Q000098:blood supply*; D010446:Peptide Fragments / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis* / Q000494:pharmacology
D010446:Peptide Fragments; D014665:Vasodilator Agents; D001920:Bradykinin