Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences

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

Standard

Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences. / Hansen, Jacob Christian; Bjørn-Yoshimoto, Walden Emil; Bisballe, Niels; Nielsen, Birgitte; Jensen, Anders A.; Bunch, Lennart.

In: Journal of Medicinal Chemistry, Vol. 59, 2016, p. 8771-8786.

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

Harvard

Hansen, JC, Bjørn-Yoshimoto, WE, Bisballe, N, Nielsen, B, Jensen, AA & Bunch, L 2016, 'Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences', Journal of Medicinal Chemistry, vol. 59, pp. 8771-8786. https://doi.org/10.1021/acs.jmedchem.6b01066

APA

Hansen, J. C., Bjørn-Yoshimoto, W. E., Bisballe, N., Nielsen, B., Jensen, A. A., & Bunch, L. (2016). Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences. Journal of Medicinal Chemistry, 59, 8771-8786. https://doi.org/10.1021/acs.jmedchem.6b01066

Vancouver

Hansen JC, Bjørn-Yoshimoto WE, Bisballe N, Nielsen B, Jensen AA, Bunch L. Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences. Journal of Medicinal Chemistry. 2016;59:8771-8786. https://doi.org/10.1021/acs.jmedchem.6b01066

Author

Hansen, Jacob Christian ; Bjørn-Yoshimoto, Walden Emil ; Bisballe, Niels ; Nielsen, Birgitte ; Jensen, Anders A. ; Bunch, Lennart. / Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences. In: Journal of Medicinal Chemistry. 2016 ; Vol. 59. pp. 8771-8786.

Bibtex

@article{9b9a49ba05884b9b911d3aaece36bd4e,
title = "Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences",
abstract = "In this study inspired by previous work on 3-substituted Asp analogues, we designed and synthesized a total of 32 β-sulfonamide Asp analogues and characterized their pharmacological properties at the excitatory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3. In addition to several potent EAAT inhibitors displaying IC50 values ∼1 μM at all three subtypes, this elaborate structure-activity relationship also identified analogues exhibiting distinct preferences or selectivities for specific transporter subtypes. Introduction of two fluorine atoms on the phenyl ring yielded analogue 4y that displayed an IC50 of 0.8 μM at EAAT1 with a 14- and 9-fold preference over EAAT2 and EAAT3, respectively. Conversely, the m-CF3-phenyl analogue 4r was a potent selective EAAT2-inhibitor (IC50 = 2.8 μM) exhibiting 30- and 50-fold selectivity over EAAT1 and EAAT3, respectively. In conclusion, even small structural differences in these β-sulfonamide Asp analogues provide analogues with diverse EAAT subtype selectivity profiles",
author = "Hansen, {Jacob Christian} and Bj{\o}rn-Yoshimoto, {Walden Emil} and Niels Bisballe and Birgitte Nielsen and Jensen, {Anders A.} and Lennart Bunch",
year = "2016",
doi = "10.1021/acs.jmedchem.6b01066",
language = "English",
volume = "59",
pages = "8771--8786",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Beta-Sulfonamido Functionalized Aspartate Analogs as Excitatory Amino Acid Transporter Inhibitors: Distinct Subtype-Selectivity Profiles Arising from Subtle Structural Differences

AU - Hansen, Jacob Christian

AU - Bjørn-Yoshimoto, Walden Emil

AU - Bisballe, Niels

AU - Nielsen, Birgitte

AU - Jensen, Anders A.

AU - Bunch, Lennart

PY - 2016

Y1 - 2016

N2 - In this study inspired by previous work on 3-substituted Asp analogues, we designed and synthesized a total of 32 β-sulfonamide Asp analogues and characterized their pharmacological properties at the excitatory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3. In addition to several potent EAAT inhibitors displaying IC50 values ∼1 μM at all three subtypes, this elaborate structure-activity relationship also identified analogues exhibiting distinct preferences or selectivities for specific transporter subtypes. Introduction of two fluorine atoms on the phenyl ring yielded analogue 4y that displayed an IC50 of 0.8 μM at EAAT1 with a 14- and 9-fold preference over EAAT2 and EAAT3, respectively. Conversely, the m-CF3-phenyl analogue 4r was a potent selective EAAT2-inhibitor (IC50 = 2.8 μM) exhibiting 30- and 50-fold selectivity over EAAT1 and EAAT3, respectively. In conclusion, even small structural differences in these β-sulfonamide Asp analogues provide analogues with diverse EAAT subtype selectivity profiles

AB - In this study inspired by previous work on 3-substituted Asp analogues, we designed and synthesized a total of 32 β-sulfonamide Asp analogues and characterized their pharmacological properties at the excitatory amino acid transporter subtypes EAAT1, EAAT2, and EAAT3. In addition to several potent EAAT inhibitors displaying IC50 values ∼1 μM at all three subtypes, this elaborate structure-activity relationship also identified analogues exhibiting distinct preferences or selectivities for specific transporter subtypes. Introduction of two fluorine atoms on the phenyl ring yielded analogue 4y that displayed an IC50 of 0.8 μM at EAAT1 with a 14- and 9-fold preference over EAAT2 and EAAT3, respectively. Conversely, the m-CF3-phenyl analogue 4r was a potent selective EAAT2-inhibitor (IC50 = 2.8 μM) exhibiting 30- and 50-fold selectivity over EAAT1 and EAAT3, respectively. In conclusion, even small structural differences in these β-sulfonamide Asp analogues provide analogues with diverse EAAT subtype selectivity profiles

U2 - 10.1021/acs.jmedchem.6b01066

DO - 10.1021/acs.jmedchem.6b01066

M3 - Journal article

C2 - 27636002

VL - 59

SP - 8771

EP - 8786

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

ER -

ID: 165167796