Identification and SAR of potent and selective non-peptide obeline somatostatin sst1 receptor antagonists.
A novel class of non-peptide somatostatin receptor ligands bearing the octahydrobenzo[g]quinoline (obeline) structural element has been identified. SAR studies have been performed that led to the discovery of derivatives with high affinity (pK(d) r sst(1) > or = 9) and selectivity (> or = 150-fold for h sst(1) over h sst(2)-h sst(5)) for somatostatin receptor subtype sst(1). In a functional assay, the compounds act as antagonists at human recombinant sst(1) receptors.
Troxler
Thomas
T
Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. thomas.troxler@novartis.com
Hoyer
Daniel
D
Langenegger
Daniel
D
Neumann
Peter
P
Pfäffli
Paul
P
Schoeffter
Philippe
P
Sorg
Dieter
D
Swoboda
Robert
R
Hurth
Konstanze
K
D000818:Animals; D006801:Humans; D008164:Luminescent Proteins / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D008164:Luminescent Proteins; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; C010497:obelin