2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors

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

Standard

2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid : resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors. / Johansen, Tommy N; Janin, Yves L; Nielsen, Birgitte; Frydenvang, Karla Andrea; Bräuner-Osborne, Hans; Stensbøl, Tine B; Vogensen, Stine B; Madsen, Ulf; Krogsgaard-Larsen, Povl.

In: Bioorganic & Medicinal Chemistry, Vol. 10, No. 7, 2002, p. 2259-66.

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

Harvard

Johansen, TN, Janin, YL, Nielsen, B, Frydenvang, KA, Bräuner-Osborne, H, Stensbøl, TB, Vogensen, SB, Madsen, U & Krogsgaard-Larsen, P 2002, '2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors', Bioorganic & Medicinal Chemistry, vol. 10, no. 7, pp. 2259-66.

APA

Johansen, T. N., Janin, Y. L., Nielsen, B., Frydenvang, K. A., Bräuner-Osborne, H., Stensbøl, T. B., Vogensen, S. B., Madsen, U., & Krogsgaard-Larsen, P. (2002). 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors. Bioorganic & Medicinal Chemistry, 10(7), 2259-66.

Vancouver

Johansen TN, Janin YL, Nielsen B, Frydenvang KA, Bräuner-Osborne H, Stensbøl TB et al. 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors. Bioorganic & Medicinal Chemistry. 2002;10(7):2259-66.

Author

Johansen, Tommy N ; Janin, Yves L ; Nielsen, Birgitte ; Frydenvang, Karla Andrea ; Bräuner-Osborne, Hans ; Stensbøl, Tine B ; Vogensen, Stine B ; Madsen, Ulf ; Krogsgaard-Larsen, Povl. / 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid : resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors. In: Bioorganic & Medicinal Chemistry. 2002 ; Vol. 10, No. 7. pp. 2259-66.

Bibtex

@article{5e20f1091f9149b5b291a0ef782aab7e,
title = "2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors",
abstract = "In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, determined using a [(3)H]AMPA binding assay and an electrophysiological model, respectively. The affinities and agonist activities obtained for (R)-TDPA (IC(50)=0.265 microM and EC(50)=6.6 microM, respectively) and (S)-TDPA (IC(50)=0.065 microM and EC(50)=20 microM, respectively) revealed a remarkably low AMPA receptor stereoselectivity, (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [(3)H](R)-aspartic acid (IC(50 ) approximately 390 microM). An enantiospecific and subtype-selective agonist activity was observed for (S)-TDPA at group I metabotropic Glu (mGlu) receptors (EC(50)=13 microM at mGlu(5) and EC(50)=95 microM at mGlu(1)).",
keywords = "Animals, CHO Cells, Cricetinae, Crystallography, X-Ray, Excitatory Amino Acid Agonists, Male, Propionic Acids, Radioligand Assay, Rats, Rats, Sprague-Dawley, Receptors, Glutamate, Stereoisomerism, Synaptosomes",
author = "Johansen, {Tommy N} and Janin, {Yves L} and Birgitte Nielsen and Frydenvang, {Karla Andrea} and Hans Br{\"a}uner-Osborne and Stensb{\o}l, {Tine B} and Vogensen, {Stine B} and Ulf Madsen and Povl Krogsgaard-Larsen",
year = "2002",
language = "English",
volume = "10",
pages = "2259--66",
journal = "Bioorganic & Medicinal Chemistry",
issn = "0968-0896",
publisher = "Pergamon Press",
number = "7",

}

RIS

TY - JOUR

T1 - 2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid

T2 - resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors

AU - Johansen, Tommy N

AU - Janin, Yves L

AU - Nielsen, Birgitte

AU - Frydenvang, Karla Andrea

AU - Bräuner-Osborne, Hans

AU - Stensbøl, Tine B

AU - Vogensen, Stine B

AU - Madsen, Ulf

AU - Krogsgaard-Larsen, Povl

PY - 2002

Y1 - 2002

N2 - In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, determined using a [(3)H]AMPA binding assay and an electrophysiological model, respectively. The affinities and agonist activities obtained for (R)-TDPA (IC(50)=0.265 microM and EC(50)=6.6 microM, respectively) and (S)-TDPA (IC(50)=0.065 microM and EC(50)=20 microM, respectively) revealed a remarkably low AMPA receptor stereoselectivity, (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [(3)H](R)-aspartic acid (IC(50 ) approximately 390 microM). An enantiospecific and subtype-selective agonist activity was observed for (S)-TDPA at group I metabotropic Glu (mGlu) receptors (EC(50)=13 microM at mGlu(5) and EC(50)=95 microM at mGlu(1)).

AB - In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, determined using a [(3)H]AMPA binding assay and an electrophysiological model, respectively. The affinities and agonist activities obtained for (R)-TDPA (IC(50)=0.265 microM and EC(50)=6.6 microM, respectively) and (S)-TDPA (IC(50)=0.065 microM and EC(50)=20 microM, respectively) revealed a remarkably low AMPA receptor stereoselectivity, (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [(3)H](R)-aspartic acid (IC(50 ) approximately 390 microM). An enantiospecific and subtype-selective agonist activity was observed for (S)-TDPA at group I metabotropic Glu (mGlu) receptors (EC(50)=13 microM at mGlu(5) and EC(50)=95 microM at mGlu(1)).

KW - Animals

KW - CHO Cells

KW - Cricetinae

KW - Crystallography, X-Ray

KW - Excitatory Amino Acid Agonists

KW - Male

KW - Propionic Acids

KW - Radioligand Assay

KW - Rats

KW - Rats, Sprague-Dawley

KW - Receptors, Glutamate

KW - Stereoisomerism

KW - Synaptosomes

M3 - Journal article

C2 - 11983523

VL - 10

SP - 2259

EP - 2266

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

SN - 0968-0896

IS - 7

ER -

ID: 40371677