Analogues of 3-Hydroxyisoxazole-Containing Glutamate Receptor Ligands Based on the 3-Hydroxypyrazole-Moiety: Design, Synthesis and Pharmacological Characterization

Lars Jørgensen; Birgitte Nielsen; Darryl S Pickering; Anders Skov Kristensen; Karla Andrea Frydenvang; Ulf Madsen; Rasmus Prætorius Clausen

doi:10.1007/s11064-014-1332-0

Analogues of 3-Hydroxyisoxazole-Containing Glutamate Receptor Ligands Based on the 3-Hydroxypyrazole-Moiety: Design, Synthesis and Pharmacological Characterization

Lars Jørgensen, Birgitte Nielsen, Darryl S Pickering, Anders Skov Kristensen, Karla Andrea Frydenvang, Ulf Madsen, Rasmus Prætorius Clausen

Department of Drug Design and Pharmacology

3 Citations (Scopus)

Abstract

A series of analogues of the glutamate receptor ligands (S)-2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propionic acid (AMPA) and AMOA were synthesized in which the 3-hydroxyisoxazole moiety was exchanged for a 3-hydroxypyrazole moiety. This exchange enables further substitution at the additional nitrogen atom in the heterocyclic core. Several of the analogues have activity at AMPA receptors equipotent to the antagonist ATPO, demonstrating that additional substitution can be accommodated in the antagonist binding site. Modelling studies offer an explanation for the pharmacological pattern observed for the compounds and suggest that this scaffold may be developed further to obtain subtype selective antagonists.

Original language	English
Journal	Neurochemical Research
Volume	39
Issue number	10
Pages (from-to)	1895-1905
Number of pages	11
ISSN	0364-3190
DOIs	https://doi.org/10.1007/s11064-014-1332-0
Publication status	Published - 24 Sept 2014

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Jørgensen, L., Nielsen, B., Pickering, D. S., Kristensen, A. S., Frydenvang, K. A., Madsen, U., & Clausen, R. P. (2014). Analogues of 3-Hydroxyisoxazole-Containing Glutamate Receptor Ligands Based on the 3-Hydroxypyrazole-Moiety: Design, Synthesis and Pharmacological Characterization. Neurochemical Research, 39(10), 1895-1905. https://doi.org/10.1007/s11064-014-1332-0

Analogues of 3-Hydroxyisoxazole-Containing Glutamate Receptor Ligands Based on the 3-Hydroxypyrazole-Moiety: Design, Synthesis and Pharmacological Characterization. / Jørgensen, Lars; Nielsen, Birgitte ; Pickering, Darryl S et al.
In: Neurochemical Research, Vol. 39, No. 10, 24.09.2014, p. 1895-1905.

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

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AU - Pickering, Darryl S

AU - Kristensen, Anders Skov

AU - Frydenvang, Karla Andrea

AU - Madsen, Ulf

AU - Clausen, Rasmus Prætorius

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Analogues of 3-Hydroxyisoxazole-Containing Glutamate Receptor Ligands Based on the 3-Hydroxypyrazole-Moiety: Design, Synthesis and Pharmacological Characterization

Abstract

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