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Fancy Bioisosteres:  Metallocene-Derived G-Protein-Coupled Receptor Ligands with Subnanomolar Binding Affinity and Novel Selectivity Profiles

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posted on 02.06.2005, 00:00 authored by Karin Schlotter, Frank Boeckler, Harald Hübner, Peter Gmeiner
Metallocene-derived bioisosteres lead to exceptionally strong binding G-protein-coupled receptor ligands, indicating substantial plasticity of the receptor excluded volume. Novel binding profiles of ferrocenylcarboxamides combining subnanomolar Ki values for the dopamine D4 receptor (1a, 0.52 nM; 1b, 0.63 nM) with superpotent serotonin 5-hydroxytryptamine1A (1a, 0.50 nM) and dopamine D3 receptor binding (1b, 0.64 nM) and selective D4 agonist properties of the ruthenocene 1c may be a starting point for highly beneficial central nervous system active drugs.

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