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Jounial of Labelled Cornpoutidsatid Radiopharmaceulicals-Vol.
XXXVlll, No. 12
Synthesis of Iodine-123 Labelled Analogues of
Imidazenil and Ethyl-Imidazenil for Studying
Benzodiazepine Receptors Using SPECT
Andrew Katsifis*,Filomena Mattner, Branko Dikic
Ljubco Najdovski and Michael Kassiou,
Australian Nuclear Science & Technology Organisation
Private Mail Bag 1, Menai NSW 2234, Sydney AUSTRALIA
The [ 1Z31]iodinated
analogues of the benzodiazepine receptor partial agonist imidazenil
and N-ethyl imidazenil have been synthesised for the study of the central
benzodiazepine receptor using SPECT. Iodoimidazenil and [ 1231]Nethyliodoimidazenil were prepared by nucleophilic bromine-iodine exchange in acetic
acid at 150". The products were purified by semi-preparative reverse-phase HPLC with
average radiochemical yields of 80% in a total synthesis time of 80 minutes. The
specific activity was determined to be greater than 2500 Ci/mmol. The radiochemical
and chemical purity assessed by radio-TLC and HPLC were found to be 98%.
Alternatively, iododestannylation reactions via the trimethyltin precursors with Na
in the presence of Chloramine-T or peracetic acid resulted in yields of only 20-25%
with the bulk of activity being lost as volatile methyl iodide.
Key Words: Imidazenil, iodine- 123,benzodiazepine receptor, partial agonist, SPECT.
Imidazenil, 6-(2'-bromophenyl)-8-fluoro-4H-imidazo[ 1,4]benzodiazepine-3-carboxamide1 is a
novel, low efficacy, [ I ,4]imidazobenzodiazepine which exhibits positive allosteric modulation of
GABAA with specific high affinity binding to the benzodiazepine sites of the GABAn receptor
complex (Ki = 0.5 nM).' It has been described as a new benzodiazepine recognition site ligand that
induces selective pharmacological effects and behavioural characteristics qualitatively different from
classical bcnzodiazepines such as diazepam, and alprazolain2
I n addition, the
pharmacological efficacy of this compound is associated with lower liabilities for sedation, muscle
* Author for correspondence
01996 by John Wiley &Sons, Ltd.
Received I 1 J u n c 1996
Revised 6 September 1996
A. Katsifis ef al.
relaxation, tolerance and dependence and is comparable to the characteristics of the partial agonists
Chronic administration of this compound in pharmacologically active doses in mice
failed to induce tolerance to the effects of this drug on GABAA receptor function.? Although the
detailed molecular interactions of partial allosteric modulators such as Imidazenil and Bretazenil have
not been established, it has been suggested that the selective pharmacological efficacy may be
attributed to preferential affinity or specific activation of subpopulations of GABAA receptors in
distinct brain regions.'.'
5 R = H,
6 R= Ethyl,
18 R = H ,
X = lz3I
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