Ergoline derivatives as highly potent and selective antagonists at the somatostatin sst1 receptor

Article abstract of DOI:10.1016/j.bmcl.2007.12.030

Non-peptidic compounds containing the octahydro-indolo[4,3-fg]quinoline (ergoline) structural element have been optimized into derivatives with high affinity (pK_d r sst₁ > 9) and selectivity (>1000-fold for h sst₁ over h sst₂-h sst₅) for the somatostatin sst₁ receptor. In functional assays, these ergolines act as antagonists at human recombinant sst₁ receptors. Pharmacokinetic studies in rodents reveal good oral bioavailability and brain penetration for some of these compounds.