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The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines

Robinson, W. J. and Taylor, A. E. and Lauga-Cami, S. and Weaver, G. W. and Arroo, R. R. J. and Kaiser, M. and Gul, S. and Kuzikov, M. and Ellinger, B. and Singh, K. and Schirmeister, T. and Botana, A. and Eurtivong, C. and Bhambra, A. S.. (2020) The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines. Eur J Med Chem, 209. p. 112871.

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Official URL: https://edoc.unibas.ch/91216/

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Abstract

Human African trypanosomiasis, or sleeping sickness, is a neglected tropical disease caused by Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense which seriously affects human health in Africa. Current therapies present limitations in their application, parasite resistance, or require further clinical investigation for wider use. Our work herein describes the design and syntheses of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines, with compound 13, the 4-(2-methoxyphenyl)-6-(pyridine-3-yl)pyrimidin-2-amine demonstrating an IC50 value of 0.38 muM and a promising off-target ADME-Tox profile in vitro. In silico molecular target investigations showed rhodesain to be a putative candidate, supported by STD and WaterLOGSY NMR experiments, however, in vitro evaluation of compound 13 against rhodesain exhibited low experimental inhibition. Therefore, our reported library of drug-like pyrimidines present promising scaffolds for further antikinetoplastid drug development for both phenotypic and target-based drug discovery.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Parasite Chemotherapy (Mäser)
UniBasel Contributors:Kaiser, Marcel
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1768-3254 (Electronic)0223-5234 (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
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Last Modified:29 Dec 2022 09:38
Deposited On:29 Dec 2022 09:38

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