A Series of 18F‐Labelled Pyridinylphenyl Amides as Subtype‐Selective Radioligands for the Dopamine D3 Receptor
Citations Over TimeTop 23% of 2010 papers
Abstract
Synthesis, biological activity, and structure-selectivity relationship (SSR) studies of a novel series of potential dopamine D3 receptor radioligands as imaging agents for positron emission tomography (PET) are reported. Considering a structurally diverse library of D3 ligands, SSR studies were performed for a new series of fluorinated pyridinylphenyl amides using CoMFA and CoMSIA methods. The in vitro D3 affinities of the predicted series of biphenyl amide ligands 9 a-d revealed single-digit to sub-nanomolar potencies (K(i)=0.52-1.6 nM), displaying excellent D3 selectivity over the D2 subtype of 110- to 210-fold for the test compounds 9 a-c. Radiofluorination by nucleophilic substitution of Br or NO(2) by (18)F led to radiochemical yields of 66-92 % for [(18)F]9 a-d. However, the specific activities of [(18)F]9 b and [(18)F]9 d were insufficient, rendering their use for in vivo studies impossible. Biodistribution studies of [(18)F]9 a and [(18)F]9 c using rat brain autoradiography revealed accumulation in the ventricles, thus indicating insufficient biokinetic properties of [(18)F]9 a and [(18)F]9 c for D3 receptor imaging in vivo.
Related Papers
- → Differential visualization of dopamine D2 and D3 receptors in rat brain(1993)23 cited
- → The dopamine D3 receptor and schizophrenia: pharmacological, anatomical and genetic approaches(1995)44 cited
- → Dopamine D2/D3 receptor agonists produce antidepressant‐like effects in the rat forced swim test through co‐activation of both receptor subtypes(2008)1 cited
- → Binding affinities for the cloned dopamine D4 and D2 receptors: Comparison of atypical and typical antipsychotic agents(1993)
- → DOPAMINE D1, D2, D3, D4 RECEPTOR GENE POLYMORPHISMS AND SCHIZOPHRENIA(1992)