Identification and SAR around N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, a selective α2C adrenergic receptor antagonist

The discovery of the CNS-penetrant and selective α2C adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13 is described. Structure–activity studies demonstrate the structural requirements for binding affinity, functional activity, and selectivity over other α2-AR subtypes.

Graphical abstractThe discovery of CNS-penetrant and selective α2C adrenergic receptor antagonist N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, 13, is described. Structure–activity studies demonstrate the requirements for binding affinity, functional activity, and selectivity over other α2-AR subtypes.Figure optionsDownload full-size imageDownload as PowerPoint slide