2. Academic Validation
  3. Structure activity relationship of selective GABA uptake inhibitors

Structure activity relationship of selective GABA uptake inhibitors

  • Bioorg Med Chem. 2015 May 15;23(10):2480-8. doi: 10.1016/j.bmc.2015.03.060.
Stine B Vogensen 1,  Lars Jørgensen 1,  Karsten K Madsen 1,  Andreas Jurik 2,  Nrupa Borkar 1,  Emiliano Rosatelli 3,  Birgitte Nielsen 1,  Gerhard F Ecker 2,  Arne Schousboe 1,  Rasmus P Clausen 4
Affiliations

Affiliations

  • 1 University of Copenhagen, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, 2100 Copenhagen, Denmark.
  • 2 University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, A-1090 Vienna, Austria.
  • 3 University of Perugia, Department of Pharmaceutical Sciences, Via del Liceo 1, Perugia I-06123, Italy.
  • 4 University of Copenhagen, Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, 2100 Copenhagen, Denmark. Electronic address: rac@sund.ku.dk.
PMID: 25882526 DOI: 10.1016/j.bmc.2015.03.060
Abstract

A series of β-amino acids with lipophilic diaromatic side chain was synthesized and characterized pharmacologically on mouse γ-amino butyric acid (GABA) transporter subtypes mGAT1-4 in order to investigate structure activity relationships (SAR) for MGAT2 (corresponding to hBGT-1). Variation in the lipophilic diaromatic side chain was probed to understand the role of the side chain for activity. This yielded several selective compounds of which the best (1R,2S)-5a was more than 10 fold selective towards Other subtypes, although potency was moderate. A docking study was performed to investigate possible binding modes of the compounds in MGAT2 suggesting a binding mode similar to that proposed for Tiagabine in hGAT1. Specific interactions between the transporter and the amino acid part of the ligands may account for a reverted preference towards MGAT2 over mGAT1.

Keywords

BGT-1; GABA uptake; Inhibitors; Tiagabine; mGAT2.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z