Structure−Activity Relationship of Triazafluorenone Derivatives as Potent and Selective mGluR1 Antagonists

SAR (structure-activity relationship) studies of triazafluorenone derivatives as potent mGluR1 antagonists are described. The triazafluorenone derivatives are non-amino acid derivatives and noncompetitive mGluR1 antagonists that bind at a putative allosteric recognition site located within the seven-transmembrane domain of the receptor. These triazafluorenone derivatives are potent, selective, and systemically active mGluR1 antagonists. Compound In, for example, was a very potent mGluR1 antagonist (IC 50 = 3 nM) and demonstrated full efficacy in various in vivo animal pain models.