Synthesis and biological evaluation of bombesin constrained analogues.

Basic Information

ID: ALA1133744

Journal: J Med Chem

Title: Synthesis and biological evaluation of bombesin constrained analogues.

Authors: Cristau M, Devin C, Oiry C, Chaloin O, Amblard M, Bernad N, Heitz A, Fehrentz JA, Martinez J.

Abstract: Analogues of bombesin which incorporate dipeptide or turn mimetics have been synthesized. One of them (compound 11) containing a seven-membered lactam ring revealed a good affinity for GRP/BN receptors on rat pancreatic acini (K(i) value of 1.7 +/- 0.4 nM) and on Swiss 3T3 cells (K(i) value of 1.0 +/- 0.2 nM). On the basis of this observation, antagonists containing the same dipeptide mimic were obtained by modification of the C-terminal part of the bombesin analogues. The most potent constrained compounds (15 and 17) were able to antagonize 1 nM bombesin-stimulated amylase secretion from rat pancreatic acini with high potency (K(i) = 21 +/- 3 and 3.3 +/- 1.0 nM, respectively) and 10(-7) M bombesin-stimulated ¿(3)Hthymidine incorporation into Swiss 3T3 cells (K(i) = 7.8 +/- 2. 0 and 0.5 +/- 0.1 nM, respectively).

CiteXplore: 10882361

DOI: 10.1021/jm990942i

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