Selective κ-opioid antagonists related to naltrindole. effect of side-chain spacer in the 5′-amidinoalkyl series

The study of κ-opioid receptor function in vivo has been hampered by the limited choice of selective κ-antagonists. Recently discovered κ-antagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It showed substantially greater κ-selectivity in binding assays than known analogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective κ-antagonists, the second basic centre may not be ideally located.