A new synthesis of flumazenil suitable for fluorine-18 labeling

摘要

In recent years,fluorinated organic compounds have assumed an increasing importance in the biomedical area owing to the concomitance of various factors such as (i)the great stability of the carbon-fluorine bond,particularly in terms of thermal and oxidative degradation (ii)the similar steric requirements of the fluorine and hydrogen atoms which allows similar metabolic pathways and (iii)teh enhanced lipophilicity which leads to improved diffusion into animal tissues of fluorinated compounds in comparison to teh corresponding hydrogenated analogues.Furthermore,~(18)_F-labeled substrates behave as tracers in the positron emission tomography (PET),which constitutes a useful tool for both pharmacokinetic in vivo studies and non-invasive clinical diagnoses.However,due to the half-life (110 min)of the fluorine-18 nuclide,one can achieve and manipulate ~(18)F-labeled substrates,provided that the fluorine atom is incorporated in the last step of the synthetic sequence.Unfortunately,this is not the case in most of the syntheses of organic fluoro derivatives.