Synthesis and sigma binding properties of 1'- and 3'-halo- and 1',3'-dihalo-N-normetazocine analogues.
The synthesis and sigma 1 and sigma 2 binding properties of several 1'- and 3'-halo- and 1',3'-dihalo-substituted analogues of (+)-N-benzyl- and (+)- and (-)-N-dimethylallyl-N-normetazocine are presented. Structure-activity relationship analyses of the binding data showed that halogen substitution at the 1'-position of these N-substituted N-normetazocine analogues had little effect on sigma 1 binding affinity, whereas 3'-halo substitution as well as 1',3'-dihalo substitution resulted in a reduction of affinity. sigma 2 affinity was increased by the presence of a 3'-bromo substituent in this series of (+)-N-substituted N-normetazocines.
Danso-Danquah
R
R
Research Triangle Institute, Research Triangle Park, North Carolina 27709, USA.
Bai
X
X
Zhang
X
X
Mascarella
S W
SW
Williams
W
W
Sine
B
B
Bowen
W D
WD
Carroll
F I
FI
D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D006168:Guinea Pigs; D006846:Hydrocarbons, Halogenated / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D009294:Narcotics / Q000138:chemical synthesis* / Q000378:metabolism* / Q000494:pharmacology; D010423:Pentazocine / Q000031:analogs & derivatives; D051381:Rats; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006846:Hydrocarbons, Halogenated; D009294:Narcotics; D017480:Receptors, sigma; C014716:normetazocine; D003496:Cyclazocine; D010423:Pentazocine