Discovery and biological profile of 4-(1-aryltriazol-4-yl)-tetrahydropyridines as an orally active new class of metabotropic glutamate receptor 1 antagonist

We describe here the discovery and the structure–activity relationship (SAR) of a series of 4-(1-Aryltriazol-4-yl)-tetrahydropyridines as novel mGluR1 antagonists. Our extensive chemical modification of lead compound 2 successfully led to fluoropyridine analogs 7j and 1 with improved in vivo antagonistic activities. Among the evaluated compounds, chemically stable urea analog 1 showed oral antagonistic activity at dose ranges of 10–30 mg/kg in an animal model.

4-(1-Aryltriazol-4-yl)-tetrahydropyridines were designed and synthesized as novel mGluR1 antagonists.Figure optionsDownload as PowerPoint slide