Synthesis and biological studies of novel neurotensin(8-13) mimetics

Novel neurotensin (NT) (8–13) (Arg⁸-Arg⁹-Pro¹⁰-Tyr¹¹-Ile¹²-Leu¹³) mimetics 3, 4 were designed by adopting all intrinsic functional groups of the native neurotensin(8–13) and using a substituted indole as a template to mimic the pharmacophore of NT(8–13). Biological studies at subtype 1 of the NT receptor showed that 3 has a 55 and 580 nM binding affinity at rat and human neurotensin receptors, respectively. As a comparison, compounds 5 and 6 were also synthesized. The binding difference between 3, 4 and 5, 6 argues the importance of the carboxylic group in achieving higher potency NT(8–13) mimetics.