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Title
  • en Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports
Creator
    • en Nakada, Kazuaki
    • en Yoshikawa, Mamie
    • en Suemasa, Akihiro
    • en Kawamura, Shuhei
    • en Kobayashi, Takaaki
    • en Masuda, Eiji
    • en Ito, Yoshihiko
    • en Hayakawa, Wataru
    • en Yamada, Shizuo
Accessrights open access
Subject
  • Other en GABA transporter
  • Other en GAT3
  • Other en BGT1
  • Other en Cyclopropane
  • Other en Conformational restriction
  • NDC 499
Description
  • Abstract en A series of cyclopropane-based conformationally restricted gamma-aminobutyric acid (GABA) analogs with stereochemical diversity, that is, the trans- and cis-2,3-methano analogs Ia and Ib and their enantiomers ent-Ia and ent-Ib, and also the trans- and cis-3,4-methano analogs IIa and IIb and their enantiomers ent-IIa and ent-Iib, were synthesized from the chiral cyclopropane units Type-a and Type-b that we developed. These analogs were systematically evaluated with four GABA transporter (GAT) subtypes. The trans-3,4-methano analog IIa had inhibitory effects on GAT3 (IC50 = 23.9 mu M) and betaine-GABA transporter1 (5.48 mu M), indicating its potential as an effective lead compound for the development of potent GAT inhibitors due to its hydrophilic and low molecular weight properties and excellent ligand efficiency. (C) 2013 Elsevier Ltd. All rights reserved.
Publisher en Pergamon-elsevier science ltd
Date
    Issued2013-09-01
Language
  • eng
Resource Type journal article
Version Type AM
Identifier HDL http://hdl.handle.net/2115/54095
Relation
  • isVersionOf DOI https://doi.org/10.1016/j.bmc.2013.06.063
  • PMID 23886812
Journal
    • PISSN 0968-0896
    • NCID AA10938083
      • en Bioorganic & medicinal chemistry
      • Volume Number21 Issue Number17 Page Start4938 Page End4950
File
Oaidate 2023-07-26