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Decahydroisoquinoline derivatives as novel non-peptidic, potent and subtype-selective somatostatin sst(3) receptor
Thomas Troxler1, Konstanze Hurth, Karl-Heinrich Schuh
1Novartis Institutes for BioMedical Research, Global Discovery Chemistry-Neuroscience, CH-4002 Basel, Switzerland. thomas.troxler@novartis.com
Abstract:
Starting from non-peptidic sst(1)-selective somatostatin receptor antagonists, first compounds with mixed sst(1)/sst(3) affinity were identified by directed structural modifications. Systematic optimization of these initial leads afforded novel, enantiomerically pure, highly potent and sst(3)-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.
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