Identification and SAR of potent and selective non-peptide obeline somatostatin sst1 receptor antagonists

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3983-7. doi: 10.1016/j.bmcl.2007.04.086. Epub 2007 Apr 29.

Abstract

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.

MeSH terms

  • Animals
  • Humans
  • Luminescent Proteins / chemistry
  • Luminescent Proteins / pharmacology*
  • Rats
  • Receptors, Somatostatin / antagonists & inhibitors*
  • Recombinant Proteins / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Luminescent Proteins
  • Receptors, Somatostatin
  • Recombinant Proteins
  • obelin