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Analogues of WAY 100635 as radiotracers for in vivo imaging of 5‐HT 1A receptors
Author(s) -
Wilson Alan A.,
Garcia Armando,
Li Jin,
Dasilva Jean N.,
Houle Sylvain
Publication year - 1999
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/(sici)1099-1344(199907)42:7<611::aid-jlcr221>3.0.co;2-l
Subject(s) - chemistry , in vivo , biodistribution , receptor , radioligand , diastereomer , stereochemistry , 5 ht receptor , antagonist , pharmacology , serotonin , in vitro , biochemistry , medicine , microbiology and biotechnology , biology
Two diastereoisomeric analogues of the potent 5‐HT 1A antagonist W A Y 100635 have been synthesized and radiolabelled with 11 C; namely trans‐ and cis‐N‐[2‐[4‐(2−methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridinyl)‐cyclohexanecarboxamide ( 3 and 4 ). Both [ 11 C]‐ 3 and [ 11 C]‐ 4 were obtained in modest yields at high specific activities by O‐[ 11 C]‐alkylation of their respective alkoxide precursors with [ 11 C]‐iodomethane. The labelled diastereoisomers were isolated by reverse‐phase HPLC and isolated as radiochemically pure formulations for in vivo experiments. Biodistribution studies in rats showed moderate brain uptake for [ 11 C]‐ 4 with little differentiation of uptake between regions rich in 5‐HT 1A receptors (e.g. hippocampus) and receptor poor regions (e.g. cerebellum). However the diastereoisomeric [ 11 C]‐ 3 possessed better brain uptake with moderate differentiation between 5‐HT 1A receptor rich and poor regions at early time points (5–30 min post‐injection). The results suggest that [ 11 C]‐ 3 may have potential as an in vivo imaging agent for 5‐HT 1A receptors. Copyright © 1999 John Wiley & Sons, Ltd.