title: Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position.
abstract: Benzo[7]annulen-7-amines 7 without further polar substituents have been reported as conformationally restricted Ro 25-6981 analogs and show unexpectedly high GluN2B affinity. Herein the corresponding 2-NO2 derivatives 8 were synthesized and pharmacologically evaluated. NO2 derivatives 8 show 5- to 10-fold higher GluN2B affinity than the unsubstituted ligands 7. Docking studies of ligands 7c and 8c reveal an important contribution of the 2-NO2-substituent in determining the binding pose and modulating the GluN2B affinity.
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany; NRW Graduate School of Chemistry, Wilhelm-Klemm-Straße 10, 48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, Germany.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Gawaskar
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schepmann
authors.affiliation: Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Via S. Agostino, 1, 62032 Camerino, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bonifazi
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie der Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany.
authors.forename: Dina
authors.initials: D
authors.lastname: Robaa
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie der Martin-Luther-Universität Halle-Wittenberg, Wolfgang-Langenbeck-Straße 4, 06120 Halle (Saale), Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sippl
authors.affiliation: Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, 48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, Germany. Electronic address: wuensch@uni-muenster.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wünsch
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D062105:Molecular Docking Simulation; D010636:Phenols / Q000737:chemistry / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981
keywords: 2-Nitrobenzo[7]annulen-7-amines; Conformational restriction; Docking studies; GluN2B antagonists; NMDA receptor; Selectivity; Structure affinity relationships