New sst_4/5-Selective Somatostatin Peptidomimetics Based on a Constrained Tryptophan Scaffold

The synthesis and biological evaluation of four peptidomimetic analogs of somatostatin based on a constrained Trp residue, 3-amino-indolo[2,3-c]azepin-2-one (Aia), are reported. It is shown that dipeptidomimetics with a d-Aia-Lys sequence, functionalized with N- and C-terminal aromatic substituents, display a good selectivity for both sst₄ and sst_5. This study allowed us to identify a new highly potent sst₅ agonist with good selectivity over the other receptors, except versus sst₄.