Structure-Guided
Design, Synthesis, and Characterization
of Next-Generation Meprin β Inhibitors
Posted on 2018-04-25 - 00:00
The
metalloproteinase meprin β 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
β 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 β and also remarkable selectivity over related
metalloproteases, i.e., matrix metalloproteases and A disintegrin
and metalloproteinases.
CITE THIS COLLECTION
DataCite
3 Biotech
3D Printing in Medicine
3D Research
3D-Printed Materials and Systems
4OR
AAPG Bulletin
AAPS Open
AAPS PharmSciTech
Abhandlungen aus dem Mathematischen Seminar der Universität Hamburg
ABI Technik (German)
Academic Medicine
Academic Pediatrics
Academic Psychiatry
Academic Questions
Academy of Management Discoveries
Academy of Management Journal
Academy of Management Learning and Education
Academy of Management Perspectives
Academy of Management Proceedings
Academy of Management Review
Ramsbeck, Daniel; Hamann, Antje; Richter, Georg; Schlenzig, Dagmar; Geissler, Stefanie; Nykiel, Vera; et al. (2018). Structure-Guided
Design, Synthesis, and Characterization
of Next-Generation Meprin β Inhibitors. ACS Publications. Collection. https://doi.org/10.1021/acs.jmedchem.8b00330
or
Select your citation style and then place your mouse over the citation text to select it.
SHARE
Usage metrics
Read the peer-reviewed publication
AUTHORS (9)
DR
Daniel Ramsbeck
AH
Antje Hamann
GR
Georg Richter
DS
Dagmar Schlenzig
SG
Stefanie Geissler
VN
Vera Nykiel
HC
Holger Cynis
SS
Stephan Schilling
MB
Mirko Buchholz
KEYWORDS
target selectivitynovel amine scaffold exhibitStructure-Guided Designmeprin β inhibitorsbioisosteric replacementmetalloprotease inhibitorsSelected compoundsNext-Generation Meprin β Inhibitorsmeprin inhibitorsnovel seriesmeprin βsulfonamide scaffolddrug targetstructure-guided designbowel diseasemetalloproteinase meprin βside effectsMorbus Alzheimer