Syntheses of two potential dopamine D4 receptor radioligands: 18F labelled chromeno[3,4-c]pyridin-5-ones

Abstract

Summary The dopamine D4 receptor is hypothesized to relate with the pathophysiology and pharmacotherapy of schizophrenia while its level in brain regions is much lower and to date no suitable tracer is available for the study of D4 receptor in vivo . Therefore, selective imaging agents for the D4 subtype are badly needed. Based on the structure-activity analysis of chromeno[3,4-c]pyridin-5-ones as dopamine D4 receptor ligands, two fluorine-18 labelled chromeno[3,4-c] pyridin-5-one derivatives, 3-(4-[18F]fluorobenzyl)-8-hydroxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one and 3-(4-[18F]fluorobenzyl)-8,9-dimethoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one were synthesized through a two-step one-pot method. Their radiochemical yields were around 19.7% (decay-corrected) and radiochemical purities were higher than 95% with specific activities of about 120 GBq/μmol.