SYNTHESIS AND BINDING AFFINITY OF CIS-(-)- AND CIS-(+)-N-ETHYLENEAMINO-N-NORDEOXYMETAZOCINE AND CIS(-)-N-NORMETAZOCINE ANALOGUES AT SIGMA-1, SIGMA-2 AND KAPPA OPIOID RECEPTORS

The synthesis of cis-(+)- and cis-(-)-N-ethyleneamino-N-nordeoxymetazocine and cis-(-)-N-normetazocine analogues is described and their affinities to sigma (1), sigma (2), and kappa opioid receptors are evaluated. The cis-(+)-deoxy compounds displayed high sigma/kappa selectivity with nanomolar K-i values for sigma (1) receptors, whereas in the cis-(-)-N-normetazocine series the compound (-)-7b was found to bind with nanomolar affinity to the kappa opioid receptor (K-i = 21.5 nM). Compound (-)-7b showed good selectivity for the kappa opioid receptor in comparison to the sigma (1), and sigma (2), sites and to the mu and delta opioid receptors. A correlation of the binding affinities between cis-(-)- and cis-(+)-N-deoxynormetazocine derivatives show that both isomers of the deoxy analogs have similar sigma (1) and sigma (2) binding profiles as the cis-(+)-N-normetazocine derivatives.