N-(3-iodophenyl)trozamicol (IPHT) and related inhibitors of vesicular acetylcholine transport: Synthesis and preliminary biological characterization

Four isomeric N-(halophenyl)trozamicol analogues (6a-d) were synthesized an d evaluated as potential vesicular acetylcholine transporter (VAChT) ligand s. Of the four compounds, N-(3-bromophenyl) trozamicol (6b) and N-(3-iodoph enyl)trozamicol (6d) displayed the highest affinity for the VAChT in vitro, whereas the para-substituted compound 6c showed the lowest affinity for th is transporter. Tissue distribution studies of N-(3-[I-125]iodophenyl)troza micol ([I-125]6d, [I-125]IPHT) suggest that the central distribution of the latter is consistent with cholinergic innervation. However, only moderate target-to-background ratios were obtained, suggesting little improvement ov er the N-(halobenzyl)trozamicols described previously. NUCL MED BIOL 26;6:6 09-617, 1999. (C) 1999 Elsevier Science Inc. All rights reserved.