Development of Novel 1,2,3,4‐Tetrahydroisoquinoline Derivatives and Closely Related Compounds as Potent and Selective Dopamine D3 Receptor Ligands
- 2 April 2004
- journal article
- Published by Wiley in ChemBioChem
- Vol. 5 (4) , 508-518
- https://doi.org/10.1002/cbic.200300784
Abstract
Based on N‐alkylated 1,2,3,4‐tetrahydroisoquinoline derivatives, which are structurally related to the partial agonist BP 897, a series of novel, selective dopamine D3receptor antagonists has been synthesised. Derivatisation included changes in the arylamide moiety and the tetrahydroisoquinoline substructure leading to compounds with markedly improved selectivities and affinities in the low nanomolar concentration range. From the 55 structures presented here, (E)‐3‐(4‐iodophenyl)‐N‐(4‐(1,2,3,4‐tetrahydroisoquinolin‐2‐yl)butyl)acrylamide (51) has high affinity (Ki(hD3)=12 nM) and a 123‐fold preference for the D3receptor relative to the D2receptor subtype. Its pharmacological profile offers the prospect of a novel radioligand as a tool for various dopamine D3‐receptor‐related in vitro and in vivo investigations.Keywords
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