Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid

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Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid. / Madsen, U; Dumpis, M A; Bräuner-Osborne, Hans; Piotrovsky, L B.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 8, No. 12, 16.06.1998, p. 1563-8.

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

Harvard

Madsen, U, Dumpis, MA, Bräuner-Osborne, H & Piotrovsky, LB 1998, 'Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid', Bioorganic & Medicinal Chemistry Letters, vol. 8, no. 12, pp. 1563-8.

APA

Madsen, U., Dumpis, M. A., Bräuner-Osborne, H., & Piotrovsky, L. B. (1998). Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid. Bioorganic & Medicinal Chemistry Letters, 8(12), 1563-8.

Vancouver

Madsen U, Dumpis MA, Bräuner-Osborne H, Piotrovsky LB. Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid. Bioorganic & Medicinal Chemistry Letters. 1998 Jun 16;8(12):1563-8.

Author

Madsen, U ; Dumpis, M A ; Bräuner-Osborne, Hans ; Piotrovsky, L B. / Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid. In: Bioorganic & Medicinal Chemistry Letters. 1998 ; Vol. 8, No. 12. pp. 1563-8.

Bibtex

@article{a71d0c896c4d482484f84146919faf99,
title = "Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid",
abstract = "Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 microM, respectively), though with activities considerably lower than Ibo (EC50 = 9.6 microM). N-Benzyl-Ibo (1c) was inactive at ionotropic EAA receptors and all three compounds were, in contrast to Ibo, inactive at metabotropic EAA receptors. Molecular mechanics calculations have been performed on Ibo, 1a-c and the potent NMDA agonist 2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA) in order to elucidate the observed structure-activity data.",
keywords = "Animals, CHO Cells, Cerebral Cortex, Cricetinae, Excitatory Amino Acid Agonists, Ibotenic Acid, Molecular Structure, Rats, Receptors, N-Methyl-D-Aspartate, Structure-Activity Relationship",
author = "U Madsen and Dumpis, {M A} and Hans Br{\"a}uner-Osborne and Piotrovsky, {L B}",
year = "1998",
month = jun,
day = "16",
language = "English",
volume = "8",
pages = "1563--8",
journal = "Bioorganic & Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Pergamon Press",
number = "12",

}

RIS

TY - JOUR

T1 - Synthesis and pharmacology of N-alkylated derivatives of the excitotoxin ibotenic acid

AU - Madsen, U

AU - Dumpis, M A

AU - Bräuner-Osborne, Hans

AU - Piotrovsky, L B

PY - 1998/6/16

Y1 - 1998/6/16

N2 - Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 microM, respectively), though with activities considerably lower than Ibo (EC50 = 9.6 microM). N-Benzyl-Ibo (1c) was inactive at ionotropic EAA receptors and all three compounds were, in contrast to Ibo, inactive at metabotropic EAA receptors. Molecular mechanics calculations have been performed on Ibo, 1a-c and the potent NMDA agonist 2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA) in order to elucidate the observed structure-activity data.

AB - Three amino-alkylated derivatives of the naturally occurring excitatory amino acid (EAA) receptor agonist ibotenic acid (Ibo) have been synthesized and tested pharmacologically. N-Methyl-Ibo (1a) and N-ethyl-Ibo (1b) were shown to be agonists at NMDA receptors (EC50 = 140 and 320 microM, respectively), though with activities considerably lower than Ibo (EC50 = 9.6 microM). N-Benzyl-Ibo (1c) was inactive at ionotropic EAA receptors and all three compounds were, in contrast to Ibo, inactive at metabotropic EAA receptors. Molecular mechanics calculations have been performed on Ibo, 1a-c and the potent NMDA agonist 2-amino-2-(3-hydroxy-5-methyl-4-isoxazolyl)acetic acid (AMAA) in order to elucidate the observed structure-activity data.

KW - Animals

KW - CHO Cells

KW - Cerebral Cortex

KW - Cricetinae

KW - Excitatory Amino Acid Agonists

KW - Ibotenic Acid

KW - Molecular Structure

KW - Rats

KW - Receptors, N-Methyl-D-Aspartate

KW - Structure-Activity Relationship

M3 - Journal article

C2 - 9873391

VL - 8

SP - 1563

EP - 1568

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

SN - 0960-894X

IS - 12

ER -

ID: 45596264