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Synthesis of 3 H‐ and 14 C‐labelled astemizole (R 43 512)
Author(s) -
Thijssen J. B. A.,
Knaeps A. G.,
Heykants J. J. P.
Publication year - 1983
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.2580200711
Subject(s) - astemizole , chemistry , moiety , tritium , high performance liquid chromatography , halogenation , cyanamide , urea , yield (engineering) , radiochemistry , stereochemistry , chromatography , organic chemistry , physics , materials science , nuclear physics , metallurgy , neuroscience , biology
Abstract Astemizole, a new antihistamine drug, was specifically labelled with tritium and 14 C at three distinct positions. Tritium was introduced either in the 4‐methoxyphenyl (II) or in the 4‐fluorophenylmethyl (IV) moiety by catalytic dehalogenation of the corresponding halogenated analogues with tritium gas, yielding 3 H‐astemizole with specific activities of 28.7 and 5.0 Ci/mmol respectively. Starting from [ 14 C]urea, [ 14 C]astemizole was synthesized with the label being placed in the 2‐position of the benzimidazole moiety. The radioactive yield of the three‐step synthesis was 22.4 %, spread over three fractions with specific activities of 4.5 mCi/mmol, 1.7 mCi/mmol and 0.4 mCi/mmol. The labelled compounds were radiochemically pure according to thin‐layer (TLC) and high‐performance liquid chromatography (HPLC).