Selective mGAT2 (BGT-1) GABA Uptake Inhibitor: Design, synthesis and pharmacological characterization

Stine Byskov Vogensen; Lars Jørgensen; Karsten Kirkegaard Madsen; Nrupa Nitin Borkar; Petrine Wellendorph; Jonas Skovgaard-Petersen; Arne Schousboe; H. Steve White; Povl Krogsgaard-Larsen; Rasmus Prætorius Clausen

doi:10.1021/jm301872x

Selective mGAT2 (BGT-1) GABA Uptake Inhibitor: Design, synthesis and pharmacological characterization

Stine Byskov Vogensen, Lars Jørgensen, Karsten Kirkegaard Madsen, Nrupa Nitin Borkar, Petrine Wellendorph, Jonas Skovgaard-Petersen, Arne Schousboe, H. Steve White, Povl Krogsgaard-Larsen, Rasmus Prætorius Clausen

33 Citations (Scopus)

Abstract

β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	56
Issue number	5
Pages (from-to)	2160-2164
Number of pages	5
DOIs	https://doi.org/10.1021/jm301872x
Publication status	Published - 14 Mar 2013

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title = "Selective mGAT2 (BGT-1) GABA Uptake Inhibitor: Design, synthesis and pharmacological characterization",

abstract = "β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.",

author = "Vogensen, {Stine Byskov} and Lars J{\o}rgensen and Madsen, {Karsten Kirkegaard} and Borkar, {Nrupa Nitin} and Petrine Wellendorph and Jonas Skovgaard-Petersen and Arne Schousboe and White, {H. Steve} and Povl Krogsgaard-Larsen and Clausen, {Rasmus Pr{\ae}torius}",

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doi = "10.1021/jm301872x",

language = "English",

volume = "56",

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T1 - Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

T2 - Design, synthesis and pharmacological characterization

AU - Vogensen, Stine Byskov

AU - Jørgensen, Lars

AU - Madsen, Karsten Kirkegaard

AU - Borkar, Nrupa Nitin

AU - Wellendorph, Petrine

AU - Skovgaard-Petersen, Jonas

AU - Schousboe, Arne

AU - White, H. Steve

AU - Krogsgaard-Larsen, Povl

AU - Clausen, Rasmus Prætorius

PY - 2013/3/14

Y1 - 2013/3/14

N2 - β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.

AB - β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.

U2 - 10.1021/jm301872x

DO - 10.1021/jm301872x

M3 - Journal article

SN - 1520-4804

VL - 56

SP - 2160

EP - 2164

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 5

ER -

Selective mGAT2 (BGT-1) GABA Uptake Inhibitor: Design, synthesis and pharmacological characterization

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