New synthetic approaches to estrogen receptor modulators: imidazo[1,2-a]pyridines

Constrained triarenes have been important templates for selective modulation of the estrogen receptor (ER). For our ER program, we sought an unexplored, synthetically accessible heterocyclic template capable of bearing a broad range of pharmacophores. Traditional approaches to these therapeutics such as raloxifene have relied on an alkoxy moiety to link the arene-based scaffold to the modulating amine group. Alternatively, aryl halide-mediated introduction of alkylene or aryl side chains has not been studied extensively. The synthetic incorporation of pharmacophoric side chains that are carbon-linked to a novel imidazopyridine-based ER recognition motif is disclosed.