Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations

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

Standard

Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations. / Huynh, Tri H. V.; Shim, Irene; Bohr, Henrik; Abrahamsen, Bjarke; Nielsen, Birgitte; Jensen, Anders A.; Bunch, Lennart.

In: Journal of Medicinal Chemistry, Vol. 55, No. 11, 2012, p. 5403-12.

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

Harvard

Huynh, THV, Shim, I, Bohr, H, Abrahamsen, B, Nielsen, B, Jensen, AA & Bunch, L 2012, 'Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations', Journal of Medicinal Chemistry, vol. 55, no. 11, pp. 5403-12. https://doi.org/10.1021/jm300345z

APA

Huynh, T. H. V., Shim, I., Bohr, H., Abrahamsen, B., Nielsen, B., Jensen, A. A., & Bunch, L. (2012). Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations. Journal of Medicinal Chemistry, 55(11), 5403-12. https://doi.org/10.1021/jm300345z

Vancouver

Huynh THV, Shim I, Bohr H, Abrahamsen B, Nielsen B, Jensen AA et al. Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations. Journal of Medicinal Chemistry. 2012;55(11):5403-12. https://doi.org/10.1021/jm300345z

Author

Huynh, Tri H. V. ; Shim, Irene ; Bohr, Henrik ; Abrahamsen, Bjarke ; Nielsen, Birgitte ; Jensen, Anders A. ; Bunch, Lennart. / Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 11. pp. 5403-12.

Bibtex

@article{b47a53579a374dfeac69d6b809150592,
title = "Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations",
abstract = "The excitatory amino acid transporters (EAATs) play essential roles in regulating the synaptic concentration of the neurotransmitter glutamate in the mammalian central nervous system. To date, five subtypes have been identified, named EAAT1-5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5 in rodents, respectively. In this paper, we present the design, synthesis, and pharmacological evaluation of seven 7-N-substituted analogues of UCPH-101/102. Analogue 9 inhibited EAAT1 in the micromolar range (IC(50) value 20 µM), whereas analogues 8 and 10 were inactive (IC(50) values >100 µM). The diastereomeric pairs 11a/11b and 12a/12b were separated by HPLC and the absolute configuration assigned by VCD technique in combination with ab initio Hartree-Fock calculations. Analogues 11a (RS-isomer) and 12b (RR-isomer) inhibited EAAT1 (IC(50) values 5.5 and 3.8 µM, respectively), whereas analogues 11b (SS-isomer) and 12a (SR-isomer) failed to inhibit EAAT1 uptake (IC(50) values >300 µM).",
author = "Huynh, {Tri H. V.} and Irene Shim and Henrik Bohr and Bjarke Abrahamsen and Birgitte Nielsen and Jensen, {Anders A.} and Lennart Bunch",
year = "2012",
doi = "10.1021/jm300345z",
language = "English",
volume = "55",
pages = "5403--12",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "11",

}

RIS

TY - JOUR

T1 - Structure-activity relationship study of selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile (UCPH-101) and absolute configurational assignment using infrared and vibrational circular dichroism spectroscopy in combination with ab initio hartree-fock calculations

AU - Huynh, Tri H. V.

AU - Shim, Irene

AU - Bohr, Henrik

AU - Abrahamsen, Bjarke

AU - Nielsen, Birgitte

AU - Jensen, Anders A.

AU - Bunch, Lennart

PY - 2012

Y1 - 2012

N2 - The excitatory amino acid transporters (EAATs) play essential roles in regulating the synaptic concentration of the neurotransmitter glutamate in the mammalian central nervous system. To date, five subtypes have been identified, named EAAT1-5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5 in rodents, respectively. In this paper, we present the design, synthesis, and pharmacological evaluation of seven 7-N-substituted analogues of UCPH-101/102. Analogue 9 inhibited EAAT1 in the micromolar range (IC(50) value 20 µM), whereas analogues 8 and 10 were inactive (IC(50) values >100 µM). The diastereomeric pairs 11a/11b and 12a/12b were separated by HPLC and the absolute configuration assigned by VCD technique in combination with ab initio Hartree-Fock calculations. Analogues 11a (RS-isomer) and 12b (RR-isomer) inhibited EAAT1 (IC(50) values 5.5 and 3.8 µM, respectively), whereas analogues 11b (SS-isomer) and 12a (SR-isomer) failed to inhibit EAAT1 uptake (IC(50) values >300 µM).

AB - The excitatory amino acid transporters (EAATs) play essential roles in regulating the synaptic concentration of the neurotransmitter glutamate in the mammalian central nervous system. To date, five subtypes have been identified, named EAAT1-5 in humans, and GLAST, GLT-1, EAAC1, EAAT4, and EAAT5 in rodents, respectively. In this paper, we present the design, synthesis, and pharmacological evaluation of seven 7-N-substituted analogues of UCPH-101/102. Analogue 9 inhibited EAAT1 in the micromolar range (IC(50) value 20 µM), whereas analogues 8 and 10 were inactive (IC(50) values >100 µM). The diastereomeric pairs 11a/11b and 12a/12b were separated by HPLC and the absolute configuration assigned by VCD technique in combination with ab initio Hartree-Fock calculations. Analogues 11a (RS-isomer) and 12b (RR-isomer) inhibited EAAT1 (IC(50) values 5.5 and 3.8 µM, respectively), whereas analogues 11b (SS-isomer) and 12a (SR-isomer) failed to inhibit EAAT1 uptake (IC(50) values >300 µM).

U2 - 10.1021/jm300345z

DO - 10.1021/jm300345z

M3 - Journal article

C2 - 22594609

VL - 55

SP - 5403

EP - 5412

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 11

ER -

ID: 38485251