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

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