Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

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

Standard

Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid. / Conti, P; De Amici, M; Bräuner-Osborne, Hans; Madsen, U; Toma, L; De Micheli, C.

In: Farmaco, Vol. 57, No. 11, 11.2002, p. 889-95.

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

Harvard

Conti, P, De Amici, M, Bräuner-Osborne, H, Madsen, U, Toma, L & De Micheli, C 2002, 'Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid', Farmaco, vol. 57, no. 11, pp. 889-95.

APA

Conti, P., De Amici, M., Bräuner-Osborne, H., Madsen, U., Toma, L., & De Micheli, C. (2002). Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid. Farmaco, 57(11), 889-95.

Vancouver

Conti P, De Amici M, Bräuner-Osborne H, Madsen U, Toma L, De Micheli C. Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid. Farmaco. 2002 Nov;57(11):889-95.

Author

Conti, P ; De Amici, M ; Bräuner-Osborne, Hans ; Madsen, U ; Toma, L ; De Micheli, C. / Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid. In: Farmaco. 2002 ; Vol. 57, No. 11. pp. 889-95.

Bibtex

@article{2499af49c6e640a79e4427faa9fc6a69,
title = "Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid",
abstract = "The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (+/-)-11 and (+/-)-12. Amino acid derivatives (+/-)-7 and (+/-)-8 were assayed at ionotropic and metabotropic glutamic acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the omega-carboxylic group of the model compounds with the 3-hydroxy-delta2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate receptors. Conversely, on passing from cis-ACPD to derivative (+/-)-8, the agonist activity at NMDA receptors is almost unaffected.",
keywords = "Amino Acids, Animals, Binding, Competitive, Cerebral Cortex, Cyclization, Cycloleucine, Electrophysiology, Excitatory Amino Acid Antagonists, Glutamates, Ligands, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Conformation, Rats, Receptors, AMPA, Receptors, Glutamate, Receptors, Kainic Acid, Receptors, Metabotropic Glutamate, Receptors, N-Methyl-D-Aspartate, Stereoisomerism, gamma-Aminobutyric Acid",
author = "P Conti and {De Amici}, M and Hans Br{\"a}uner-Osborne and U Madsen and L Toma and {De Micheli}, C",
year = "2002",
month = nov,
language = "English",
volume = "57",
pages = "889--95",
journal = "Il Farmaco",
issn = "0014-827X",
publisher = "Elsevier France * Editions Scientifiques et Medicales",
number = "11",

}

RIS

TY - JOUR

T1 - Synthesis and pharmacology of 3-hydroxy-delta2-isoxazoline-cyclopentane analogues of glutamic acid

AU - Conti, P

AU - De Amici, M

AU - Bräuner-Osborne, Hans

AU - Madsen, U

AU - Toma, L

AU - De Micheli, C

PY - 2002/11

Y1 - 2002/11

N2 - The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (+/-)-11 and (+/-)-12. Amino acid derivatives (+/-)-7 and (+/-)-8 were assayed at ionotropic and metabotropic glutamic acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the omega-carboxylic group of the model compounds with the 3-hydroxy-delta2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate receptors. Conversely, on passing from cis-ACPD to derivative (+/-)-8, the agonist activity at NMDA receptors is almost unaffected.

AB - The synthesis and pharmacology of two potential glutamic acid receptor ligands are described. Preparation of the bicyclic 3-hydroxy-delta2-isoxazoline-cyclopentane derivatives (+/-)-7 and (+/-)-8 was accomplished via 1,3-dipolar cycloaddition of bromonitrile oxide to suitably protected 1-amino-cyclopent-3-enecarboxylic acids. Their structure was established using a combination of 1H NMR spectroscopy and molecular mechanics calculations carried out on the intermediate cycloadducts (+/-)-11 and (+/-)-12. Amino acid derivatives (+/-)-7 and (+/-)-8 were assayed at ionotropic and metabotropic glutamic acid receptor subtypes and their activity compared with that of trans-ACPD and cis-ACPD. The results show that the replacement of the omega-carboxylic group of the model compounds with the 3-hydroxy-delta2-isoxazoline moiety abolishes or reduces drastically the activity at the metabotropic glutamate receptors. Conversely, on passing from cis-ACPD to derivative (+/-)-8, the agonist activity at NMDA receptors is almost unaffected.

KW - Amino Acids

KW - Animals

KW - Binding, Competitive

KW - Cerebral Cortex

KW - Cyclization

KW - Cycloleucine

KW - Electrophysiology

KW - Excitatory Amino Acid Antagonists

KW - Glutamates

KW - Ligands

KW - Magnetic Resonance Spectroscopy

KW - Models, Molecular

KW - Molecular Conformation

KW - Rats

KW - Receptors, AMPA

KW - Receptors, Glutamate

KW - Receptors, Kainic Acid

KW - Receptors, Metabotropic Glutamate

KW - Receptors, N-Methyl-D-Aspartate

KW - Stereoisomerism

KW - gamma-Aminobutyric Acid

M3 - Journal article

C2 - 12484537

VL - 57

SP - 889

EP - 895

JO - Il Farmaco

JF - Il Farmaco

SN - 0014-827X

IS - 11

ER -

ID: 45613736