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Synthesis of a potential M 1 muscarinic agent [ 76 Br]bromocaramiphen
Author(s) -
Strijckmans V.,
Hunter D. H.,
Dolle F.,
Coulon C.,
Loc'h C.,
Mazière B.
Publication year - 1996
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(199605)38:5<471::aid-jlcr854>3.0.co;2-q
Subject(s) - chemistry , muscarinic acetylcholine receptor , metabolite , lipophilicity , ligand (biochemistry) , striatum , in vivo , yield (engineering) , stereochemistry , radiochemistry , medicinal chemistry , receptor , biochemistry , medicine , dopamine , microbiology and biotechnology , materials science , metallurgy , biology
[ 76 Br]bromocaramiphen was prepared from the iodo‐analogue by a Cu + nucleophilic bromodeiodination exchange. The radiolabelling yield was 40–45%. The radiochemical and chemical purities assessed by radio‐TLC and HPLC were 98%. The precursor, iodocaramiphen, was synthesized from commercially available 1‐phenylcyclopentanecarboxylic acid with a 10% overall yield in a 5 step procedure. This synthesis includes the formation of 1‐(p‐nitrophenyl)‐, 1‐(p‐aminophenyl)‐ and 1‐(p‐iodophenyl) cyclopentane carboxylic acid. In vivo studies in rats showed high uptake in brain. A 10% decrease was observed by coinjecting with the radiotracer a cold load of QNB, a non subtype selective muscarinic ligand. The metabolite study performed in the pons tissues indicated that there was still 92% of unchanged radiotracer 30 min p.i. After coinjection of dextrometorphan, a sigma ligand, a reduction of the radioactivity uptake by 20 to 27% was observed in the pons, the cortex, the striatum and the cerebellum. These data suggest that [ 76 Br]bromocaramiphen is not a potential probe for investigating the status of central M 1 muscarinic receptors because of its high lipophilicity (log P 7.4 = 2.4) and its affinity for sigma sites.