Phenylethylamide derivatives of the C-terminal tetrapeptide of gastrin. Potent inhibitors of gastrin-stimulated acid secretion.
Peptide analogues of the C-terminal tetrapeptide of gastrin in which the phenylalanine had been replaced were synthesized and their biological activity on acid secretion evaluated. Compounds Boc-Trp-Leu-Asp phenylethylamide 6, Boc-beta-Ala-Trp-Leu-Asp phenylethylamide 9, Boc-Trp-Leu-Asp p-fluorophenylethylamide 19, Boc-Trp-psi(CH2NH)-Leu-Asp phenylethylamide 23, Boc-Trp-Leu-Asp 2,2-diphenylethylamide 15, and Boc-D Trp-Leu-Asp 2,2-diphenylethylamide 21, in which the phenylalanine had been replaced by phenylethylamine, p-fluorophenylethylamine or 2,2-diphenylethylamine were synthesized. None of these derivatives showed activity on acid secretion in the anaesthetized rat at doses as high as 5 mg/kg. However, they were potent inhibitors of gastrin-induced acid secretion, with ED50 varying from 0.1 to 0.6 mg/kg.
D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D005750:Gastric Juice / Q000187:drug effects; D005755:Gastrins / Q000138:chemical synthesis / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009904:Optical Rotation; D051381:Rats; D013329:Structure-Activity Relationship; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
D005755:Gastrins; D007202:Indicators and Reagents; D013758:Tetragastrin; C008530:minigastrin