Peptidic and non-peptidic neurotensin analogs

The structure-activity relationship studies of neurotensin and its analogs have revealed that i) the C-terminal hexapeptide NT (8-13) (H-Arg⁸-Arg⁹-Pro¹⁰-Tyr¹¹- Ile¹²-Leu¹³-OH) is equipotent to or more potent than the native NT(1-13) and retains all the intrinsic biological properties of neurotensin, ii) the N-terminal peptide fragment up to NT(1-7) does not significantly contribute to the binding potency, iii) Pro¹⁰ that can form a reverse-turn conformation is required, iv) an aromatic amino acid is important at Tyr¹¹ position, v) the lipophilic side chain of Leu¹³ is also crucial to the biological activities, and, vi) L-form amino acids are essential at critical positions for the binding potency. In addition to many peptidic neurotensin analogs, highly potent, orally active, and selective non-peptidic analogs as antagonists of NT receptors, which have long lasting effects and the ability to cross the bloodbrain barrier (e. g. SR 142948 A and SR 48692), have been discovered.