Straightforward and effective synthesis of γ-aminobutyric acid transporter subtype 2-selective acyl-substituted azaspiro[4.5]decanes. Issue 2 (15th January 2016)

• Record Type: Journal Article
• Authors: Ma, Xiaofeng; Lubin, Hodney; Ioja, Enikő; Kékesi, Orsolya; Simon, Ágnes; Apáti, Ágota; Orbán, Tamás I.; Héja, László; Kardos, Julianna; Markó, István E.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 2(2016)
• Page Start: 417
• Page End: 423
• Publication Date: 2016-01-15
• Subjects: Azaspiro[4.5]decane scaffold -- γ-Aminobutyric acid (GABA) -- GABA transporter subtype GAT2 (slc6a13) -- ω-Amino acid selectivity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.11.100
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.