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Pharmaceuticals 2016, 9(1), 2; doi:10.3390/ph9010002

3,1-Benzothiazines, 1,4-Benzodioxines and 1,4-Benzoxazines as Inhibitors of Matriptase-2: Outcome of a Focused Screening Approach

1
Pharmaceutical Chemistry I, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, D-53115 Bonn, Germany
2
Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, SI-1000 Ljubljana, Slovenia
These authors contributed equally.
*
Author to whom correspondence should be addressed.
Academic Editor: Jean Jacques Vanden Eynde
Received: 27 October 2015 / Revised: 5 January 2016 / Accepted: 7 January 2016 / Published: 13 January 2016
(This article belongs to the Collection Choices of the Journal)
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Abstract

The liver enzyme matriptase-2 is a multi-domain, transmembrane serine protease with an extracellular, C-terminal catalytic domain. Synthetic low-molecular weight inhibitors of matriptase-2 have potential as therapeutics to treat iron overload syndromes, in particular in patients with β-thalassemia. A sub-library of 64 compounds was screened for matriptase-2 inhibition and several active compounds were identified. (S)-Ethyl 2-(benzyl(3-((4-carbamidoylphenoxy)methyl)-2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-2-oxoacetate ((S)-12) showed an IC50 value of less than 10 µM. Structure-activity relationships were discussed and proposals to design new matriptase-2 inhibitors were made. View Full-Text
Keywords: benzamidines; 4H-3,1-benzothiazin-4-ones; 2,3-dihydro-1,4-benzodioxines; 3,4-dihydro-2H-1,4-benzoxazines; matriptase-2; protease inhibition benzamidines; 4H-3,1-benzothiazin-4-ones; 2,3-dihydro-1,4-benzodioxines; 3,4-dihydro-2H-1,4-benzoxazines; matriptase-2; protease inhibition
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Roydeva, P.G.; Beckmann, A.-M.; Stirnberg, M.; Cesar, J.; Kikelj, D.; Ilaš, J.; Gütschow, M. 3,1-Benzothiazines, 1,4-Benzodioxines and 1,4-Benzoxazines as Inhibitors of Matriptase-2: Outcome of a Focused Screening Approach. Pharmaceuticals 2016, 9, 2.

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