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

Pharmaceuticals
Polya G RoydevaMichael Gütschow

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.

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Citations

Dec 7, 2018·Future Medicinal Chemistry·Agata Gitlin-DomagalskaKrzysztof Rolka
Jan 23, 2019·The Indian Journal of Medical Research·Kanjaksha Ghosh, Kinjalka Ghosh
Dec 12, 2019·The Journal of Organic Chemistry·V P Rama Kishore PuttaChandi C Malakar

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