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The Synthesis and Evaluation of Fluoro‐, Trifluoromethyl‐, and Iodomuscimols as GABA Agonists
Author(s) -
Abdul Manan Mohd Abdul Fatah,
Cordes David B.,
Slawin Alexandra M. Z.,
Bühl Michael,
Liao Vivian W. Y.,
Chua Han. C.,
Chebib Mary,
O'Hagan David
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201701443
Subject(s) - muscimol , gabaa receptor , isoxazole , chemistry , trifluoromethyl , agonist , receptor , stereochemistry , potency , pharmacology , biochemistry , biology , organic chemistry , in vitro , alkyl
Halogenated analogues of the neurotoxic alkaloid muscimol were prepared with fluorine, iodine or trifluoromethyl at the 4 position of the isoxazole ring system. These compounds were investigated as agonists for GABA A receptors. Only the C‐4 fluorine‐containing analogue proved to be an active compound in these assays. The fluoro analogue was less active than muscimol, however it showed differential activity between synaptic (α 1 β 2 γ 2 ) and extrasynaptic (α 4 β 2 γ) GABA A receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α 4 β 2 γ) receptor.