Straightforward and effective synthesis of γ-aminobutyric acid transporter subtype 2-selective acyl-substituted azaspiro[4.5]decanes

Xiaofeng Ma, Hodney Lubin, Eniko Ioja, Orsolya Kékesi, Ágnes Simon, Ágota Apáti, Tamás I. Orbán, László Héja, Julianna Kardos, István E. Markó

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Supply of major metabolites such as γ-aminobutyric acid (GABA), β-alanine and taurine is an essential instrument that shapes signalling, proper cell functioning and survival in the brain and peripheral organs. This background motivates the synthesis of novel classes of compounds regulating their selective transport through various fluid-organ barriers via the low-affinity γ-aminobutyric acid (GABA) transporter subtype 2 (GAT2). Natural and synthetic spirocyclic compounds or therapeutics with a range of structures and biological activity are increasingly recognised in this regard. Based on pre-validated GABA transport activity, straightforward and efficient synthesis method was developed to provide an azaspiro[4.5]decane scaffold, holding a variety of charge, substituent and 3D constrain of spirocyclic amine. Investigation of the azaspiro[4.5]decane scaffold in cell lines expressing the four GABA transporter subtypes led to the discovery of a subclass of a GAT2-selective compounds with acyl-substituted azaspiro[4.5]decane core.

Original languageEnglish
Pages (from-to)417-423
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number2
DOIs
Publication statusPublished - Jan 15 2016

Keywords

  • Azaspiro[4.5]decane scaffold
  • GABA transporter subtype GAT2 (slc6a13)
  • γ-Aminobutyric acid (GABA)
  • ω-Amino acid selectivity

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Straightforward and effective synthesis of γ-aminobutyric acid transporter subtype 2-selective acyl-substituted azaspiro[4.5]decanes'. Together they form a unique fingerprint.

  • Cite this