Synthesis and biological evaluation of novel N-substituted nipecotic acid derivatives with an alkyne spacer as GABA uptake inhibitors

Publication date: Available online 1 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Krisztián Tóth, Georg Höfner, Klaus T. Wanner
In this study, we present the synthesis and structure-activity relationships (SAR) of novel N–substituted nipecotic acid derivatives closely related to SNAP-5114 (2) in the pursuit of finding new and potent mGAT4 selective inhibitors. By the use of iminium ion chemistry, a series of new N-substituted nipecotic acid derivatives containing a variety of heterocycles, and an alkyne spacer were synthesized. Biological evaluation of the prepared compounds showed, how the inhibitory potency and subtype selectivity for the murine GABA transporters (mGATs) were influenced by the performed modifications.

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