Development of α5-SOP002
We re-synthesised  6,6-dimethyl-3-(2-hydroxyethyl) thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one that has demonstrated selectivity for the benzodiazepine binding site and high negative allosteric modulation for the α5 GABAAR sub-type following its published route, from the parent compound (Atack, 2010; Sternfeld et al., 2004) to develop hybrid derivatives (parent compound, shown in Figure 1 (A)), full details of the synthetic steps are detailed in supplementary scheme 1 (B) (see also Sung, Lee, 1992).  There were two main sites for modification, which we explored via replacement of the triazole moiety or the oxazole which enabled us to explore late-stage modification in order to synthesise hybrid analogues to improve potency as a negative allosteric modulator acting on α5 GABAA Rs.