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1st Joint European Conference on Therapeutic Targets and Medicinal Chemistry (TTMC 2015)
Open AccessFeature PaperCommunication

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

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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
*
Author to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Jean Jacques Vanden Eynde
Pharmaceuticals 2016, 9(1), 2; https://doi.org/10.3390/ph9010002
Received: 27 October 2015 / Revised: 5 January 2016 / Accepted: 7 January 2016 / Published: 13 January 2016
(This article belongs to the Special Issue Choices of the Journal)
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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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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