Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

Esben J Bjerrum; Anders S Kristensen; Darryl S Pickering; Jeremy R Greenwood; Birgitte Nielsen; Tommy Liljefors; Arne Schousboe; Hans Bräuner-Osborne; Ulf Madsen; Darryl Pickering

doi:10.1021/jm020588f

Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)

Esben J Bjerrum, Anders S Kristensen, Darryl S Pickering, Jeremy R Greenwood, Birgitte Nielsen, Tommy Liljefors, Arne Schousboe, Hans Bräuner-Osborne, Ulf Madsen, Darryl Pickering

Research output: Contribution to journal › Journal article › Research › peer-review

42 Citations (Scopus)

Abstract

On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. The potent AMPA receptor activity was strongly desensitizing and the neurotoxicity similar to AMPA. Thus, Cl-HIBO is the most subtype selective agonist reported to date on GluR1/2, and offers a new standard for selectively studying subtypes of AMPA receptors.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	46
Issue number	11
Pages (from-to)	2246-9
Number of pages	3
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm020588f
Publication status	Published - 2003

Bibliographical note

Keywords: Animals; Cell Survival; Cells, Cultured; Cerebral Cortex; Electrophysiology; Excitatory Amino Acid Agonists; Isoxazoles; Mice; Models, Molecular; Neurons; Oocytes; Propionates; Propionic Acids; Radioligand Assay; Rats; Receptors, AMPA; Receptors, Metabotropic Glutamate; Stereoisomerism; Structure-Activity Relationship; Xenopus laevis

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10.1021/jm020588f

Cite this

Bjerrum, E. J., Kristensen, A. S., Pickering, D. S., Greenwood, J. R., Nielsen, B., Liljefors, T., Schousboe, A., Bräuner-Osborne, H., Madsen, U., & Pickering, D. (2003). Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO). Journal of Medicinal Chemistry, 46(11), 2246-9. https://doi.org/10.1021/jm020588f

Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO). / Bjerrum, Esben J; Kristensen, Anders S; Pickering, Darryl S et al.
In: Journal of Medicinal Chemistry, Vol. 46, No. 11, 2003, p. 2246-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Bjerrum, EJ, Kristensen, AS, Pickering, DS, Greenwood, JR, Nielsen, B, Liljefors, T, Schousboe, A, Bräuner-Osborne, H , Madsen, U & Pickering, D 2003, 'Design, synthesis, and pharmacology of a highly subtype-selective GluR1/2 agonist, (RS)-2-amino-3-(4-chloro-3-hydroxy-5-isoxazolyl)propionic acid (Cl-HIBO)', Journal of Medicinal Chemistry, vol. 46, no. 11, pp. 2246-9. https://doi.org/10.1021/jm020588f

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abstract = "On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. The potent AMPA receptor activity was strongly desensitizing and the neurotoxicity similar to AMPA. Thus, Cl-HIBO is the most subtype selective agonist reported to date on GluR1/2, and offers a new standard for selectively studying subtypes of AMPA receptors.",

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AU - Bjerrum, Esben J

AU - Kristensen, Anders S

AU - Pickering, Darryl S

AU - Greenwood, Jeremy R

AU - Nielsen, Birgitte

AU - Liljefors, Tommy

AU - Schousboe, Arne

AU - Bräuner-Osborne, Hans

AU - Madsen, Ulf

AU - Pickering, Darryl

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AB - On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. The potent AMPA receptor activity was strongly desensitizing and the neurotoxicity similar to AMPA. Thus, Cl-HIBO is the most subtype selective agonist reported to date on GluR1/2, and offers a new standard for selectively studying subtypes of AMPA receptors.

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