Design, Synthesis, and Evaluation of 5′??Diphenyl Nucleoside Analogues as Inhibitors of the Plasmodium falciparum dUTPase

…, C Bosch??Navarrete, JA Musso??Buendía…

Index: Hampton, Shahienaz E.; Baragana, Beatriz; Schipani, Alessandro; Bosch-Navarrete, Cristina; Musso-Buendia, J. Alexander; Recio, Eliseo; Kaiser, Marcel; Whittingham, Jean L.; Roberts, Shirley M.; Shevtsov, Mikhail; Brannigan, James A.; Kahnberg, Pia; Brun, Reto; Wilson, Keith S.; Gonzalez-Pacanowska, Dolores; Johansson, Nils Gunnar; Gilbert, Ian H. ChemMedChem, 2011 , vol. 6, # 10 p. 1816 - 1831

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Citation Number: 18

Abstract

Deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase) is a potential drug target for malaria. We previously reported some 5′-tritylated deoxyuridine analogues (both cyclic and acyclic) as selective inhibitors of the Plasmodium falciparum dUTPase. Modelling studies indicated that it might be possible to replace the trityl group with a diphenyl moiety, as two of the phenyl groups are buried, whereas the third is exposed to solvent. Herein we report the synthesis ...