Novel thienopyrrole glycogen phosphorylase inhibitors: Synthesis, in vitro SAR and crystallographic studies

Novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase are described, in particular: SAR, hepatocyte activity and binding at the dimer interface site of the rabbit muscle enzyme (X-ray crystallography). Two series of novel thienopyrrole inhibitors of recombinant human liver glycogen phosphorylase a (GPa) which are effective in reducing glucose output from rat hepatocytes are described. Representative compounds have been shown to bind at the dimer interface site of the rabbit muscle enzyme by X-ray crystallography.