Patent · US Expired

Novel C-terminal gastrin antagonists

US4997950A · kind A · utility

30Cited by
0References
1Claims
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Inventors

Key dates

Filing dateApr 20, 1989
Grant dateMar 5, 1991
Priority date
Expiry dateApr 20, 2009

Classification

  • Technology area (CPC A)Human Necessities
  • CPC primaryA61K38/00
  • WIPO fieldPharmaceuticals
  • WIPO sectorChemistry

Abstract

A series of derivatives of the biologically active C-terminus of gastrin was synthesized to study the structural activity of the molecule and also to determine the smallest and highest affinity inhibitor of gastrin. Earlier work speculated that a peptide resistant to dipeptidase contained in a receptor would be an effective gastrin antagonist. Methods: Five dogs with both chronic gastric fistulae and Heidenhein pouches were used. After an 18 hour fast, gastric juice was collected both from the gastric fistula and pouch over 200 minutes at 10 minute intervals. MMC (Migrating Motor Complex) was monitored by a small balloon in the gastric antrum. Collections were initiated at the beginning of phase I of the MMC and were obtained under 3 conditions: Control, pentagastrin infusion (0.5 .mu.g/Kg/h, i.v.) and pentagastrin+peptide infusion (Indole propionic acid [IPA]- Leu-Asp-Phenethyl amine [PEA], Boc-Trp-Leu-.beta.Ala, IPA-Leu-.beta.Ala, or Boc-Trp-Leu-Asp-methyl meta Aminobenzoic acid {mABAOMe] at 20 pmol/kg/h for 70 min.). Pentagastrin infusion was started immediately before the next peak of the MMC. Peptides were infused 60 minutes after starting pentagastrin infusion. Results: All f…

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