Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position

Sandeep Gawaskar; Dirk Schepmann; Alessandro Bonifazi; Dina Robaa; Wolfgang Sippl; Bernhard Wünsch

doi:10.1016/j.bmcl.2015.10.076

Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position

Sandeep Gawaskar, Dirk Schepmann, Alessandro Bonifazi, Dina Robaa, Wolfgang Sippl, Bernhard Wünsch

Research output: Contribution to journal › Article › peer-review

17 Scopus citations

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.

Original language	English (US)
Pages (from-to)	5748-5751
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2015.10.076
State	Published - Dec 15 2015
Externally published	Yes

Keywords

2-Nitrobenzo[7]annulen-7-amines
Conformational restriction
Docking studies
GluN2B antagonists
NMDA receptor
Selectivity
Structure affinity relationships

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2015.10.076

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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.",

keywords = "2-Nitrobenzo[7]annulen-7-amines, Conformational restriction, Docking studies, GluN2B antagonists, NMDA receptor, Selectivity, Structure affinity relationships",

author = "Sandeep Gawaskar and Dirk Schepmann and Alessandro Bonifazi and Dina Robaa and Wolfgang Sippl and Bernhard W{\"u}nsch",

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doi = "10.1016/j.bmcl.2015.10.076",

language = "English (US)",

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AU - Gawaskar, Sandeep

AU - Schepmann, Dirk

AU - Bonifazi, Alessandro

AU - Robaa, Dina

AU - Sippl, Wolfgang

AU - Wünsch, Bernhard

PY - 2015/12/15

Y1 - 2015/12/15

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KW - 2-Nitrobenzo[7]annulen-7-amines

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KW - Docking studies

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KW - NMDA receptor

KW - Selectivity

KW - Structure affinity relationships

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Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position

Abstract

Keywords

ASJC Scopus subject areas

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