The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines.
Basic Information
ID: ALA4732068
Journal: Eur J Med Chem
Title: The discovery of novel antitrypanosomal 4-phenyl-6-(pyridin-3-yl)pyrimidines.
Authors: Robinson WJ,Taylor AE,Lauga-Cami S,Weaver GW,Arroo RRJ,Kaiser M,Gul S,Kuzikov M,Ellinger B,Singh K,Schirmeister T,Botana A,Eurtivong C,Bhambra AS
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 IC value of 0.38 μM 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.
CiteXplore: 33070078
DOI: 10.1016/j.ejmech.2020.112871
Patent ID: ┄