Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor

Alan P. Kozikowski, Werner Tückmantel, Ian J. Reynolds, Jarda T. Wroblewski

Research output: Contribution to journalArticle

Abstract

A variety of derivatives of azetidine-2,4-dicarboxylic acid were synthesized and examined for their ability to stimulate 45Ca2+ uptake in cultures of cerebellar granule cells. Of the compounds tested, the cis-azetidine-2,4-dicarboxylic acid (10f) was found to be the most potent agent in potentiating glutamate, aspartate, or N-methyl-D-aspartate (NMDA) stimulated 45Ca2+ uptake at the NMDA receptor. The mechanism of action of 10f was further investigated in [3H]MK-801 binding assays and [3H]GABA release from cultured embryonic rat forebrain neurons. All of the results from the functional studies of azetidine 10f are consistent with a selectivity of action at the NMDA receptor. Moreover, azetidine 10f appears to exhibit a dual type of action, behaving as a glutamate-like agonist at higher concentrations and as a positive modulator at concentrations below 50 μM.

Original languageEnglish (US)
Pages (from-to)1561-1571
Number of pages11
JournalJournal of Medicinal Chemistry
Volume33
Issue number6
StatePublished - 1990
Externally publishedYes

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Bioactivity
N-Methyl-D-Aspartate Receptors
Modulators
Glutamic Acid
Excitatory Amino Acid Agonists
Dizocilpine Maleate
N-Methylaspartate
Prosencephalon
Aspartic Acid
gamma-Aminobutyric Acid
Neurons
Rats
Assays
Derivatives
azetidine
azetidine-2,4-dicarboxylic acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Kozikowski, A. P., Tückmantel, W., Reynolds, I. J., & Wroblewski, J. T. (1990). Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor. Journal of Medicinal Chemistry, 33(6), 1561-1571.

Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor. / Kozikowski, Alan P.; Tückmantel, Werner; Reynolds, Ian J.; Wroblewski, Jarda T.

In: Journal of Medicinal Chemistry, Vol. 33, No. 6, 1990, p. 1561-1571.

Research output: Contribution to journalArticle

Kozikowski, AP, Tückmantel, W, Reynolds, IJ & Wroblewski, JT 1990, 'Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor', Journal of Medicinal Chemistry, vol. 33, no. 6, pp. 1561-1571.
Kozikowski, Alan P. ; Tückmantel, Werner ; Reynolds, Ian J. ; Wroblewski, Jarda T. / Synthesis and bioactivity of a new class of rigid glutamate analogues. Modulators of the N-methyl-D-aspartate receptor. In: Journal of Medicinal Chemistry. 1990 ; Vol. 33, No. 6. pp. 1561-1571.
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