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A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Compound
(−)23b was identified as one which showed good separation of NR2B and hERG activities.
A novel series of annulated tricyclic compounds was synthesized and evaluated as NMDA/NR2B antagonists. Structure–activity development was directed towards in vitro optimization of NR2B activity and selectivity over the hERG K
+ channel. Preferred compounds were subsequently evaluated for selectivity in an α
1-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.