SYNTHESIS AND SIGMA-BINDING PROPERTIES OF 1'-HALO-N-NORMETAZOCINE AND3'-HALO-N-NORMETAZOCINE AND 1',3'-DIHALO-N-NORMETAZOCINE ANALOGS

The synthesis and sigma 1 and sigma 2 binding properties of several 1' - and 3'-halo- and 1',3'-dihalosubstituted analogues of (+)-N-benzyl- and (+)- and (-)-N-dimethylallyl-N-normetazocine are presented. Struct ure-activity relationship analyses of the binding data showed that hal ogen substitution at the 1'-position of these N-substituted N-normetaz ocine analogues had little effect an ol binding affinity, whereas 3'-h alo substitution as well as 1',3'-dihalo substitution resulted in a re duction of affinity. sigma 2 affinity was increased by the presence of a 3'-bromo substituent in this series of (+)-N-substituted N-normetaz ocines.