Novel 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran derivatives as selective α2C-adrenergic receptor antagonists

The synthesis of a series of 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methyl-2-arylbenzofuran and 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran-2-carboxamide derivatives as novel α2C-adrenergic receptor antagonists are described. Their affinity at three different human α2-adrenergic receptors is reported, and some of these compounds exhibited high affinity for the α2C-adrenergic receptor with high subtype selectivity. Among them, compound 10e has been found to show the anti-l-dopa-induced dyskinetic activity in marmosets. The structure–activity relationship of these compounds is also discussed.

Graphical abstractThe synthesis and SAR studies of a series of novel 4-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)methylbenzofuran derivatives as highly selective α2C-adrenergic receptor antagonists are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide