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  4. Structure-guided design, synthesis, and characterization of next-generation meprin v inhibitors
 
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2018
Journal Article
Titel

Structure-guided design, synthesis, and characterization of next-generation meprin v inhibitors

Abstract
The metalloproteinase meprin v emerged as a current drug target for the treatment of a number of disorders, among those fibrosis, inflammatory bowel disease and Morbus Alzheimer. A major obstacle in the development of metalloprotease inhibitors is target selectivity to avoid side effects by blocking related enzymes with physiological functions. Here, we describe the structure-guided design of a novel series of compounds, based on previously reported highly active meprin v inhibitors. The bioisosteric replacement of the sulfonamide scaffold gave rise to a next generation of meprin inhibitors. Selected compounds based on this novel amine scaffold exhibit high activity against meprin v and also remarkable selectivity over related metalloproteases, i.e., matrix metalloproteases and A disintegrin and metalloproteinases.
Author(s)
Ramsbeck, Daniel
Fraunhofer IZI-MWT
Hamann, Antje
Fraunhofer IZI-MWT
Richter, Georg
Fraunhofer IZI-MWT
Schlenzig, Dagmar
Fraunhofer IZI-MWT
Geißler, Stefanie
Fraunhofer IZI-MWT
Nykiel, Vera
Fraunhofer IZI-MWT
Cynis, Holger
Fraunhofer IZI-MWT
Schilling, Stephan
Fraunhofer IZI-MWT
Buchholz, Mirko
Fraunhofer IZI-MWT
Zeitschrift
Journal of medicinal chemistry
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DOI
10.1021/acs.jmedchem.8b00330
Language
English
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Fraunhofer-Institut für Zelltherapie und Immunologie IZI
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