Novel Amino-pyrazole Ureas with Potent In Vitro and In Vivo Antileishmanial Activity

Visceral leishmaniasis is a severe parasitic disease that is one of the most neglected tropical diseases. Treatment options are limited, and there is an urgent need for new therapeutic agents. Following an HTS campaign and hit optimization, a novel series of amino-pyrazole ureas has been identified...

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Veröffentlicht in:Journal of medicinal chemistry 2015-12, Vol.58 (24), p.9615-9624
Hauptverfasser: Mowbray, Charles E, Braillard, Stéphanie, Speed, William, Glossop, Paul A, Whitlock, Gavin A, Gibson, Karl R, Mills, James E. J, Brown, Alan D, Gardner, J. Mark F, Cao, Yafeng, Hua, Wen, Morgans, Garreth L, Feijens, Pim-Bart, Matheeussen, An, Maes, Louis J
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Sprache:eng
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Zusammenfassung:Visceral leishmaniasis is a severe parasitic disease that is one of the most neglected tropical diseases. Treatment options are limited, and there is an urgent need for new therapeutic agents. Following an HTS campaign and hit optimization, a novel series of amino-pyrazole ureas has been identified with potent in vitro antileishmanial activity. Furthermore, compound 26 shows high levels of in vivo efficacy (>90%) against Leishmania infantum, thus demonstrating proof of concept for this series.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.5b01456