Selective kappa-opioid antagonists related to naltrindole. Effect of side-chain spacer in the 5 '-amidinoalkyl series

The study of kappa -opioid receptor function in vivo has been hampered by t he limited choice of selective kappa -antagonists. Recently discovered cc-a ntagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It sho wed substantially greater kappa -selectivity in binding assays than known a nalogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective kappa -antagonists, the second basic cent re may not be ideally located. (C) 2000 Elsevier Science Ltd. All rights re served.