Synthesis of analogues of the Des‐Phe‐NH2C‐terminal hexapeptide of cholecystokinin showing gastrin antagonist activity

Four analogues of Z-CCK-27–32-NH2, Z-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH2, a cholecystokinin receptor antagonist have been synthesized by solution methodology. In these analogues, Z-Tyr(SO3-)-Nle-Gly-Trp-Met-Asp-NH216, Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-NH217, BOC-Tyr(SO3-)-Met-Gly-Trp-Met-Asp-NH224 and Boc-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp-NH225 methionyl residues were replaced by norleucyl residues. Preliminary biological activity on gastrin-induced acid secretion, in rat, are reported. These derivatives proved to antagonize the action of gastrin, with ED 50 of between 0.5 and 3 mg/kg.