GABA_A receptor modulators are structurally almost as diverse as their target protein. A plethora of heterocyclic scaffolds has been described as modulating this extremely important receptor family. Some made it into clinical trials and, even on the market, some were dismissed. This review focuses on the synthetic accessibility and potential for library synthesis of GABA_A receptor modulators containing at least one heterocyclic scaffold, which were disclosed within the last 10 years.

The synthesis of novel pyrazolothienopyridinone derivatives as potential GABA_A receptor modulators was performed and is herein described. A crucial step of the synthesis involving handling unstable aminothiophenes was managed via two different synthetic strategies delivering a set of 8 target compounds. Graphical abstract