Tricyclic thienopyridine–pyrimidones/thienopyrimidine–pyrimidones as orally efficacious mGluR1 antagonists for neuropathic pain

Introduction of small unsaturated alkylamino groups at the 4-position of the A-ring of the tricyclic framework (triazafluorenone) afforded extremely potent and selective mGluR1 antagonists with desirable properties. Compounds 11q and 11s are active in the SNL pain model with ED50s 3.3 and 6.4 mg/kg respectively. Metabolic outcome of propargyl amino moiety was studied.

Graphical abstractA series of highly potent and selective mGluR1 antagonists have been discovered and demonstrated efficacy in animal model for pain.Figure optionsDownload full-size imageDownload as PowerPoint slide