Issue 7, 2012
From the journal:

MedChemComm

New 3-amidinophenylalanine-derived inhibitors of matriptase†

Maya Hammami,a   Eggert Rühmann,a   Eva Maurer,b   Andreas Heine,a   Michael Gütschow,b   Gerhard Klebea  and  Torsten Steinmetzer*a  

* Corresponding authors

a Institute of Pharmaceutical Chemistry, Philipps University Marburg, Marbacher Weg 6, D-35032 Marburg, Germany
E-mail: steinmetzer@staff.uni-marburg.de
Fax: +49 6421 2825901
Tel: +49 6421 2825900

b Pharmaceutical Institute, Pharmaceutical Chemistry I, Rheinische Friedrich-Wilhelms-Universität Bonn, An der Immenburg 4, D-53121 Bonn, Germany

Abstract

New 3-amidinophenylalanine-derived matriptase inhibitors were developed and tested against the related trypsin-like serine proteases matriptase-2, thrombin and factor Xa. The strongest matriptase inhibition was found for compounds containing an N-terminal 2′,4′-dichloro- or 2′,4′-dimethoxy-biphenyl-3-sulfonyl group. The combination with a C-terminal piperidyl-cyclohexylurea residue provided the first monobasic matriptase inhibitor with a Ki value < 3 nM and excellent selectivity over thrombin. The X-ray structure of a representative analogue in complex with thrombin superimposed with matriptase provides information regarding the selectivity profile observed in this study.

Graphical abstract: New 3-amidinophenylalanine-derived inhibitors of matriptase

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Article information

DOI
https://doi.org/10.1039/C2MD20074K
Article type
Concise Article
Submitted
20 Mar 2012
Accepted
06 May 2012
First published
08 May 2012

Med. Chem. Commun., 2012,3, 807-813

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New 3-amidinophenylalanine-derived inhibitors of matriptase

M. Hammami, E. Rühmann, E. Maurer, A. Heine, M. Gütschow, G. Klebe and T. Steinmetzer, Med. Chem. Commun., 2012, 3, 807 DOI: 10.1039/C2MD20074K

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