Premium
Rapid synthesis of [ 18 F]SR46349B, a potent and selective 5‐HT 2 receptor antagonist
Author(s) -
Tan Pingzhong,
Fowler Joanna S.,
Ding YuShin,
Schlyer David J.
Publication year - 1995
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580360803
Subject(s) - chemistry , radiosynthesis , radioligand , potassium carbonate , yield (engineering) , nucleophilic substitution , chemical synthesis , hydrolysis , ketone , antagonist , silica gel , stereochemistry , receptor , medicinal chemistry , chromatography , organic chemistry , in vitro , biochemistry , materials science , microbiology and biotechnology , in vivo , metallurgy , biology
F‐18 labeled SR46349B, a highly potent and selective 5‐HT 2 receptor antagonist, was synthesized as a potential radioligand for PET studies of brain 5‐HT 2 receptors. Nucleophilic aromatic substitution of trans ‐1‐(2‐nitrophenyl)‐3‐(4‐methoxymethoxyphenyl)‐2‐propenone ( 10 ) with NCA [ 18 F]fluoride in the presence of potassium carbonate and kryptofix‐222, followed by HCl hydrolysis, gave F‐18 labeled 12 , which was purified by a novel combination of C‐18 Sep‐Pak and silica column chromatography. Subsequent condensation of [ 18 F]ketone 12 with Me 2 NCH 2 CH 2 ONH 2 gave a mixture of [ 18 F]SR46349B and its geometric isomer, which was separated by high performance liquid chromatography. The three step hot synthesis of [ 18 F]SR46349B required 170 min. and gave a specific activity of 1140 Ci/mmol, 5% radiochemical yield (EOB) and 96% radiochemical purity.