Selective mGAT2 (BGT-1) GABA uptake inhibitors: design, synthesis, and pharmacological characterization

  • J Med Chem. 2013 Mar 14;56(5):2160-4. doi: 10.1021/jm301872x.
Stine B Vogensen  1 ,  Lars Jørgensen ,  Karsten K Madsen ,  Nrupa Borkar ,  Petrine Wellendorph ,  Jonas Skovgaard-Petersen ,  Arne Schousboe ,  H Steve White ,  Povl Krogsgaard-Larsen ,  Rasmus P Clausen
Affiliations
  • 1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark.
PMID: 23398473 DOI: 10.1021/jm301872x
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.

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