title: Ergoline derivatives as highly potent and selective antagonists at the somatostatin sst 1 receptor.
abstract: 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 sst(1)>9) and selectivity (>1000-fold for h sst(1) over h sst(2)-h sst(5)) for the somatostatin sst(1) receptor. In functional assays, these ergolines act as antagonists at human recombinant sst(1) receptors. Pharmacokinetic studies in rodents reveal good oral bioavailability and brain penetration for some of these compounds.
authors.affiliation: Neuroscience Chemistry, Novartis Institutes for BioMedical Research, WSJ-088.3.06, CH-4002 Basel, Switzerland. thomas.troxler@novartis.com
authors.forename: Thomas
authors.initials: T
authors.lastname: Troxler
authors.forename: Albert
authors.initials: A
authors.lastname: Enz
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoyer
authors.forename: Daniel
authors.initials: D
authors.lastname: Langenegger
authors.forename: Peter
authors.initials: P
authors.lastname: Neumann
authors.forename: Paul
authors.initials: P
authors.lastname: Pfäffli
authors.forename: Philippe
authors.initials: P
authors.lastname: Schoeffter
authors.forename: Konstanze
authors.initials: K
authors.lastname: Hurth
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004873:Ergolines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013004:Somatostatin / Q000502:physiology
chemical_list: D004873:Ergolines; D017481:Receptors, Somatostatin; D013004:Somatostatin