Synthesis and evaluation of novel tricyclic benzo[4.5]cyclohepta[1.2]pyridine derivatives as NMDA/NR2B antagonists

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• 作者：Charles J. McIntyre ; John A. McCauley ; Bohumil Bednar ; Rodney A. Bednar ; John W. Butcher ; David A. Claremon ; Michael E. Cunningham ; Roger M. Freidinger ; Stanley L. Gaul ; Carl F. Homnick ; Ken S. Koblan
• 关键词：2B heterocycle
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2009
• 出版时间：1 September 2009
• 年：2009
• 卷：19
• 期：17
• 页码：5132-5135
• 全文大小：579 K

文摘

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 α₁-adrenergic receptor binding counter-screen and a cell-based assay of NR2B activity.