Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors

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

Standard

Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors. / Kayser, Silke; Hansen, Jacob C; Staudt, Markus; Moroz, Aleksandra; Larsen, Younes; Temperini, Piero; Yi, Feng; Syrenne, Jed T; Krogsgaard-Larsen, Niels; Iliadis, Stylianos; Nielsen, Birgitte; Hansen, Kasper B; Pickering, Darryl S; Bunch, Lennart.

In: ACS Chemical Neuroscience, Vol. 11, 2020, p. 674-701.

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

Harvard

Kayser, S, Hansen, JC, Staudt, M, Moroz, A, Larsen, Y, Temperini, P, Yi, F, Syrenne, JT, Krogsgaard-Larsen, N, Iliadis, S, Nielsen, B, Hansen, KB, Pickering, DS & Bunch, L 2020, 'Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors', ACS Chemical Neuroscience, vol. 11, pp. 674-701. https://doi.org/10.1021/acschemneuro.0c00003

APA

Kayser, S., Hansen, J. C., Staudt, M., Moroz, A., Larsen, Y., Temperini, P., Yi, F., Syrenne, J. T., Krogsgaard-Larsen, N., Iliadis, S., Nielsen, B., Hansen, K. B., Pickering, D. S., & Bunch, L. (2020). Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors. ACS Chemical Neuroscience, 11, 674-701. https://doi.org/10.1021/acschemneuro.0c00003

Vancouver

Kayser S, Hansen JC, Staudt M, Moroz A, Larsen Y, Temperini P et al. Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors. ACS Chemical Neuroscience. 2020;11:674-701. https://doi.org/10.1021/acschemneuro.0c00003

Author

Kayser, Silke ; Hansen, Jacob C ; Staudt, Markus ; Moroz, Aleksandra ; Larsen, Younes ; Temperini, Piero ; Yi, Feng ; Syrenne, Jed T ; Krogsgaard-Larsen, Niels ; Iliadis, Stylianos ; Nielsen, Birgitte ; Hansen, Kasper B ; Pickering, Darryl S ; Bunch, Lennart. / Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors. In: ACS Chemical Neuroscience. 2020 ; Vol. 11. pp. 674-701.

Bibtex

@article{8b6ef5178c794fc3a63ade2b0ea0e184,
title = "Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors",
abstract = "Competitive antagonists for ionotropic glutamate receptors (iGluRs) are highly valuable tool compounds for studying health and disease states in the central nervous system. However, only few subtype selective tool compounds are available and the discovery of antagonists with novel iGluR subtype selectivity profiles remains a profound challenge. In this paper, we report an elaborate structure-activity relationship (SAR) study of the parental scaffold 2,3-trans-3-carboxy-3-phenyl-proline by the synthesis of 40 new analogues. Three synthetic strategies were employed with two new strategies of which one being a highly efficient and fully enantioselective strategy based on C(sp3)-H activation methodology. The SAR study led to the conclusion that selectivity for the NMDA receptors was a general trend when adding substituents in the 5'-position. Selective NMDA receptor antagonists were obtained with high potency (IC50 values as low as 200 nM) and 3-34-fold preference for GluN1/GluN2A over GluN1/GluN2B-D NMDA receptors.",
author = "Silke Kayser and Hansen, {Jacob C} and Markus Staudt and Aleksandra Moroz and Younes Larsen and Piero Temperini and Feng Yi and Syrenne, {Jed T} and Niels Krogsgaard-Larsen and Stylianos Iliadis and Birgitte Nielsen and Hansen, {Kasper B} and Pickering, {Darryl S} and Lennart Bunch",
year = "2020",
doi = "10.1021/acschemneuro.0c00003",
language = "English",
volume = "11",
pages = "674--701",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",

}

RIS

TY - JOUR

T1 - Stereoselective Synthesis of New (2S,3R)-3-Carboxyphenyl)pyrrolidine-2-carboxylic Acid Analogues Utilizing a C(sp3)-H Activation Strategy and Structure-Activity Relationship Studies at the Ionotropic Glutamate Receptors

AU - Kayser, Silke

AU - Hansen, Jacob C

AU - Staudt, Markus

AU - Moroz, Aleksandra

AU - Larsen, Younes

AU - Temperini, Piero

AU - Yi, Feng

AU - Syrenne, Jed T

AU - Krogsgaard-Larsen, Niels

AU - Iliadis, Stylianos

AU - Nielsen, Birgitte

AU - Hansen, Kasper B

AU - Pickering, Darryl S

AU - Bunch, Lennart

PY - 2020

Y1 - 2020

N2 - Competitive antagonists for ionotropic glutamate receptors (iGluRs) are highly valuable tool compounds for studying health and disease states in the central nervous system. However, only few subtype selective tool compounds are available and the discovery of antagonists with novel iGluR subtype selectivity profiles remains a profound challenge. In this paper, we report an elaborate structure-activity relationship (SAR) study of the parental scaffold 2,3-trans-3-carboxy-3-phenyl-proline by the synthesis of 40 new analogues. Three synthetic strategies were employed with two new strategies of which one being a highly efficient and fully enantioselective strategy based on C(sp3)-H activation methodology. The SAR study led to the conclusion that selectivity for the NMDA receptors was a general trend when adding substituents in the 5'-position. Selective NMDA receptor antagonists were obtained with high potency (IC50 values as low as 200 nM) and 3-34-fold preference for GluN1/GluN2A over GluN1/GluN2B-D NMDA receptors.

AB - Competitive antagonists for ionotropic glutamate receptors (iGluRs) are highly valuable tool compounds for studying health and disease states in the central nervous system. However, only few subtype selective tool compounds are available and the discovery of antagonists with novel iGluR subtype selectivity profiles remains a profound challenge. In this paper, we report an elaborate structure-activity relationship (SAR) study of the parental scaffold 2,3-trans-3-carboxy-3-phenyl-proline by the synthesis of 40 new analogues. Three synthetic strategies were employed with two new strategies of which one being a highly efficient and fully enantioselective strategy based on C(sp3)-H activation methodology. The SAR study led to the conclusion that selectivity for the NMDA receptors was a general trend when adding substituents in the 5'-position. Selective NMDA receptor antagonists were obtained with high potency (IC50 values as low as 200 nM) and 3-34-fold preference for GluN1/GluN2A over GluN1/GluN2B-D NMDA receptors.

U2 - 10.1021/acschemneuro.0c00003

DO - 10.1021/acschemneuro.0c00003

M3 - Journal article

C2 - 32065744

VL - 11

SP - 674

EP - 701

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

ER -

ID: 237104971