The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists

Mohd Abdul Fatah Abdul Manan; David Cordes; Alexandra Slawin; Michael Buehl; Vivian Liao; Han Chua; Mary Chebib; David O'Hagan

doi:10.1002/chem.201701443

The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists

Mohd Abdul Fatah Abdul Manan, David Cordes, Alexandra Slawin, Michael Buehl, Vivian Liao, Han Chua, Mary Chebib, David O'Hagan

Research output: Contribution to journal › Article › peer-review

Abstract

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 (α₁β₂γ₂) and extrasynaptic (α₄β₂γ) GABA_A receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α₄β₂γ) receptor.

Original language	English
Pages (from-to)	10848-10852
Number of pages	5
Journal	Chemistry - A European Journal
Volume	23
Issue number	45
Early online date	24 Jul 2017
DOIs	https://doi.org/10.1002/chem.201701443
Publication status	Published - 10 Aug 2017

Keywords

Muscimol
GABA agonists
GABA receptors
Fluorination
Trifluoromethyl
Iodination

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10.1002/chem.201701443

O'Hagan_2017_CEJ_GABAagonists_AAM
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1002/chem.201701443
Accepted author manuscript, 1.44 MB
SuppInfo_CEJ_GABAagonists
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This work has been made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at: https://doi.org/10.1002/chem.201701443
Accepted author manuscript, 3.96 MB

The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists (dataset)
Abdul Manan, M. A. F. (Creator), Cordes, D. B. (Creator), Slawin, A. M. Z. (Creator), Buehl, M. (Creator), Liao, V. (Creator), Chua, H. (Creator), Chebib, M. (Creator) & O'Hagan, D. (Creator), Cambridge Crystallographic Data Centre, 2017
https://dx.doi.org/10.5517/ccdc.csd.cc1nnx6f and 4 more links, https://dx.doi.org/10.5517/ccdc.csd.cc1nnx7g, https://dx.doi.org/10.5517/ccdc.csd.cc1nnx8h, https://dx.doi.org/10.5517/ccdc.csd.cc1nnx9j, https://dx.doi.org/10.5517/ccdc.csd.cc1nnxbk (show fewer)
Dataset

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title = "The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists",

abstract = "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 GABAA 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 (α1β2γ2) and extrasynaptic (α4β2γ) GABAA receptors, having a similar potency to the neurotransmitter GABA for the extrasynaptic (α4β2γ) receptor.",

keywords = "Muscimol, GABA agonists, GABA receptors, Fluorination, Trifluoromethyl, Iodination",

author = "{Abdul Manan}, {Mohd Abdul Fatah} and David Cordes and Alexandra Slawin and Michael Buehl and Vivian Liao and Han Chua and Mary Chebib and David O'Hagan",

note = "MAFAM acknowledges the Ministry of Education of Malaysia and Universiti Teknologi MARA for a scholarship. MC acknowledges the funding support of the Australian National Health and Medical Research Council (APP1081733).",

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AU - Abdul Manan, Mohd Abdul Fatah

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AU - Slawin, Alexandra

AU - Buehl, Michael

AU - Liao, Vivian

AU - Chua, Han

AU - Chebib, Mary

AU - O'Hagan, David

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The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists

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The synthesis and evaluation of fluoro-, trifluoromethyl, and iodomuscimols as GABA agonists (dataset)

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