Syntheses and biological activities of potent bombesin receptor antagonists

Bombesin receptor antagonists are potential therapeutic agents due to their ability to act as inhibitors of cellular proliferation. On the basis of ou r hypothesis concerning the mechanism of action of gastrin associating an a ctivating enzyme to the receptor and on the results reported in the literat ure, we have synthesized bombesin analogs which have been modified in the C -terminal part. Potent bombesin receptor antagonists were obtained by repla cement of Leu-13 with a statyl residue or with a residue bearing an hydroxy l group in place of the carbonyl function of Leu-13. Several inhibitors wer e able to recognize the bombesin receptor on rat pancreatic acini and antag onized bombesin stimulated amylase secretion in the nanomolar range. These compounds were also able to recognize the bombesin receptor and to inhibit [H-3] thymidine incorporation in 3T3 cells with the same potency.