A series of compounds synthesized from a key intermediate in the total synthesis of Scleritodermin A containing a novel conjugated thiazole moiety, 2-(1-amino-2-p-hydroxyphenylethane)-4-(4-carboxy-2,4-dimethyl-2Z,4E-propadiene)-thiazole (ACT), were discovered to be potent inhibitors of protein tyrosine phosphatase 1B, with IC50 values in the low micromolar range. Structure–activity relationships around the scaffold were investigated and some compounds exhibited more potent PTP1B inhibitory activity and improved specificities compared with the original hit.
