Acyclic phosph(on)ate inhibitors of Plasmodium falciparum hypoxanthine-guanine-xanthine phosphoribosyltransferase
The pathogenic protozoa responsible for malaria lack enzymes for the de novo synthesis of purines and rely on purine salvage from the host. In Plasmodium falciparum (Pf), hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) converts hypoxanthine to inosine monophosphate and is essential for purine salvage making the enzyme an anti-malarial drug target. We have synthesized a number of simple acyclic aza-C-nucleosides and shown that some are potent inhibitors of Pf HGXPRT while showing excellent selectivity for the Pf versus the human enzyme.
Clinch, Keith,Crump, Douglas R.,Evans, Gary B.,Hazleton, Keith Z.,Mason, Jennifer M.,Schramm, Vern L.,Tyler, Peter C.
p. 5629 - 5646
(2013/09/02)
PHOSPHORIBOSYLTRANSFERASE INHIBITORS AND USES THEREOF
The invention relates to compounds of formula (I) that are inhibitors of hypoxanthine and/or guanine purine phosphoribosyltransferases and to pharmaceutical compositions containing the compounds, processes for preparing the compounds, and methods of treating diseases or conditions in which it is desirable to inhibit hypoxanthine and/or guanine purine phosphoribosyltransferases. Such diseases include malaria.
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(2012/11/14)
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