Decahydroisoquinoline derivatives as novel non-peptidic,potent and subtype-selective somatostatin sst3 receptor antagonists

Starting from non-peptidic sst₁-selective somatostatin receptor antagonists, first compounds with mixed sst₁/sst₃ affinity were identified by directed structural modifications. Systematic optimization of these initial leads afforded novel, enantiomerically pure, highly potent and sst₃-subtype selective somatostatin antagonists based on a (4S,4aS,8aR)-decahydroisoquinoline-4-carboxylic acid core moiety. These compounds can efficiently be synthesized and show promising PK properties in rodents.