Synthesis and in vitro evaluation of iodine labelled pyrazolo[1,5-a]pyridines as highly selective dopamine D4 receptor ligands

Two I-131-labelled radioligands, namely 3-(4-[I-131]iodophenylpiperazin-1-y l-methyl)-pyrazolo[1,5-a]pyridine and 3-(4-chlorophenylpiperazin-1-ylmethyl )7-[I-131]iodopyrazolo[1,5-a]pyridine, which are required for studies or bi nding of these ligands to the D4 receptor, have been synthesized in 80% and 32% radiochemical yields, respectively; the radiochemical purity in each c ase was > 97%. For the second radioligand a kit preparation, based on iodod estannylation followed by solid-phase extraction, was possible. In vitro ch aracterization using CHO-cells expressing different dopamine receptor subty pes gave K-i values of 3.1 and 2.6 nM. Both radioligands are highly selecti ve for the D4 subtype as compared to other dopamine subtypes. Copyright (C) 2001 John Wiley & Sons, Ltd.