Substituted 3-phenyltropane analogs of cocaine: synthesis, inhibition of binding at cocaine recognition sites, and positron emission tomography imaging.
It is now accepted that (-)-cocaine binds to specific recognition sites associated with monoamine transporters in the mammalian brain. In this study, several analogs of 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester were prepared and their potency for inhibiting the binding of [3H]-3 beta-(4-fluorophenyl)tropane-2 beta-carboxylic acid methyl ester to primate caudate-putamen was evaluated. The synthesis and binding affinity of 3 beta-(3,4- dichlorophenyl)tropane-2 beta-carboxylic acid methyl ester, one of the most potent cocaine congeners yet reported, is presented. The feasibility of synthesizing high-affinity ligands for cocaine recognition sites and their suitability as PET imaging ligands for cocaine receptors in vivo is demonstrated.
Meltzer
P C
PC
Organix Inc., Woburn, Massachusetts 01801.
Liang
A Y
AY
Brownell
A L
AL
Elmaleh
D R
DR
Madras
B K
BK
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D013329:Structure-Activity Relationship; D014055:Tomography, Emission-Computed; D014326:Tropanes / Q000138:chemical synthesis* / Q000378:metabolism
D014326:Tropanes; D003042:Cocaine