Prof. Dr. Bernhard Wünsch
"No positions via CiM-IMPRS in 2024"
Design, synthesis and pharmacological evaluation of novel receptor ligands and fluorinated PET-tracers
Chemistry
Development
Molecular Modeling
The group of Bernhard Wünsch is working on the development and synthesis of novel ligands for various receptors in the central nervous system. Among these, the ionotropic glutamate receptor (NMDA receptor) is one of the primary targets of research. Due to the key role of the NMDA receptor in the pathophysiology of neurodegenerative diseases and neuroinflammatory processes, receptor ligands modulating the activity of the NMDA receptor represent a promising class of potential therapeutics. Since many details regarding the subunit arrangement, tissue distribution and genetic upregulation of receptor expression are still not fully understood, selective PET tracers can both serve as diagnostic or valuable pharmacological tools to explore the mechanism of neurodegenerative diseases.
Starting from lead compounds developed in the working group, different synthetic strategies to introduce fluorine atoms into the scaffold of the ligands are being explored while optimizing or retaining the receptor affinity and selectivity. Of particular interest are ligands selectively targeting the GluN2B subunit of the NMDA receptor. While molecular modelling techniques (docking studies) are used to design novel ligands, the receptor affinity and selectivity of synthesized compounds will also be evaluated in binding experiments. The enantioselective synthesis of GluN2B selective antagonists and in-vitro studies of metabolic stability and plasma protein binding experiments are further projects in this area of research.
Vita
- 1979 - 1983: Studies of Pharmacy, Universität München
- 1984: Approbation as Pharmacist
- 1987: Dr. rer. nat., Ludwig-Maximilians-Universität München (F. Eiden)
- 1993: Habilitation, Ludwig-Maximilians-Universität München (Pharmaceutical Chemistry)
- 1995: Johann-Wolfgang-Döbereiner-Preis der Deutschen Pharmazeutischen Gesellschaft (German Pharmaceutical Society)
- 1996 - 2002: Universitätsprofessor C3, Pharmaceutical Chemistry, Universität Freiburg
- Since 2002: Universitätsprofessor C4, Pharmaceutical Chemistry, University of Münster
- 2005 - 2006: Dean of the Faculty of Chemistry and Pharmacy, University of Münster
- 2010: Chairman of the international congress “Frontiers in Medicinal Chemistry”, March 14.-17, 2010, Münster
- Since 2014: Expert at the Institute of Medical and Pharmaceutical Examinations, IMPP, Commission “general, inorganic and organic chemistry”
- Since 2016: DFG-Fachkollegiat, Fachkollegium 205 Medizin
- Since 2019: Spokesperson of the research training group “chemical biology of ion channels (Chembion)”
- Since 2019: Chairman of the Fachgruppe Pharmazeutische/Medizinische Chemie der Deutschen Pharmazeutischen Gesellschaft
Selected references
F. Börgel, M. Szermerski, J. A. Schreiber, L. Temme, N. Strutz-Seebohm, K. Lehmkuhl, D. Schepmann, S. M. Ametamey, G. Seebohm, T. J. Schmidt, B. Wünsch. Synthesis and pharmacological evaluation of enantiomerically pure GluN2B selective NMDA receptor antagonists.ChemMedChem 2018, 13, 1580 - 1587.
G. Tangherlini, D. V. Kalinin, D. Schepmann, T. Che, N. Mykicki, S. Ständer, K. Loser, B. Wünsch. Development of novel quinoxaline-based κ-opioid receptor agonists for the treatment of neuroinflammation. J. Med. Chem. 2019, 62, 893 - 907.
E. Kronenberg, F. Weber, S. Brune, D. Schepmann, C. Almansa, K. Friedland, E. Laurini, S. Pricl, B. Wünsch. Synthesis and structure-affinity relationships of spirocyclic benzopyrans with exocyclic amino moiety. J. Med. Chem. 2019, 62, 4204 - 4217.
P. Bunse, C. Schlepphorst, F. Glorius, M. Kitamura, B. Wünsch. Short and atom-economic enantioselective synthesis of the σ1-receptor ligands (S) - and (R)-fluspidine – important tools for positron emission tomography studies. J. Org. Chem. 2019, 84, 13744 - 13754.
J. A. Schreiber, D. Schepmann, B. Frehland, S. Thum, M. Datunashvili, T. Budde, M. Hollmann, N. Strutz-Seebohm, B. Wünsch, G. Seebohm. A common mechanism allows selective targeting of GluN2B subunit-containing N-methyl-D-aspartarte receptors.Commun. Biol. 2019, 2, 420.
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