A concise and efficient synthesis of flumazenil and its precursor for radiolabeling with fluorine-18

摘要

Presently there is a strong interest in developing radioligands for in vivo imaging the GABA_A-Bz site with positron emission tomography (PET). Flumazenil (1), a high-affinity GABA_A-Bz site inverse agonist, is amenable for ~(11)C and ~(18)F-labeling. The current methods for synthesis of 1 and its precursor for ~(18)-labeling are not ideal and restrict structure-activity relationship (SAR) development. Herein we present a novel and less troublesome synthesis of 1 and its cognates to aid in the development of improved radioligands for PET imaging of GABA_A-Bz site.