Synthesis of new carbon-11-labeled carboxamide derivatives as potential PET dopamine D 3 receptor radioligands

Abstract

Carbon-11-labeled carboxamide derivatives, ( E)-4-fluoro- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide, ([ 11C] 3a), ( E)-4-chloro- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide ([ 11C] 3b), ( E)-4-bromo- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide, ([ 11C] 3c), ( E)-4-methoxy- N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)cinnamoylamide ([ 11C] 3d), N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)naphthyl-2-carboxamide ([ 11C]BP897, [ 11C] 3e), and N-(4-(4-(2-[ 11C]methoxyphenyl)piperazin-1-yl)butyl)biphenyl-4-carboxamide ([ 11C] 3f), have been synthesized as new potential PET radioligands for imaging of dopamine D 3 receptors. The target tracers were prepared by O-[ 11C]methylation of their corresponding precursors using [ 11C]CH 3OTf and isolated by a simplified solid-phase extraction (SPE) purification procedure in 50–65% radiochemical yields decay corrected to end of bombardment (EOB), 20 min overall synthesis time, and 111–148 GBq/μmol specific activity at end of synthesis (EOS).