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The chemical structures were designed with the aim to study selectivity of the inhibitors for <jats:italic>Pf<\/jats:italic>HGXPRT over human HGPRT. The newly prepared compounds contain 9\u2010deazahypoxanthine connected to a phosphonate group <jats:italic>via<\/jats:italic> a five\u2010atom\u2010linker bearing a nitrogen atom (N2\u2032) as a branching point. All compounds, with the additional phosphonate group(s) in the second aliphatic linker attached to N2\u2032 atom, were low micromolar inhibitors of <jats:italic>Pf<\/jats:italic>HGXPRT with low to modest selectivity for the parasite enzyme over human HGPRT. The effect of the addition of different chemical groups\/linkers to N2\u2032 atom on the inhibition constants and selectivity is discussed.<\/jats:p>","DOI":"10.1002\/cmdc.202300211","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T09:56:34Z","timestamp":1685699794000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["N2\u2032\u2010Branched Acyclic Nucleoside Phosphonates Containing 9\u2010Deazahypoxanthine as Inhibitors of <i>Plasmodium falciparum<\/i> 6\u2010Oxopurine Phosphoribosyltransferase"],"prefix":"10.1002","volume":"18","author":[{"given":"Karol\u00edna","family":"Va\u0148kov\u00e1","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences  Flemingovo n\u00e1m. 2 166 10 Prague 6 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne T.","family":"Keough","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences University of Queensland  Brisbane 4072 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Hockov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences  Flemingovo n\u00e1m. 2 166 10 Prague 6 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke W.","family":"Guddat","sequence":"additional","affiliation":[{"name":"School of Chemistry and Molecular Biosciences University of Queensland  Brisbane 4072 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-679X","authenticated-orcid":false,"given":"Zlatko","family":"Janeba","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences  Flemingovo n\u00e1m. 2 166 10 Prague 6 Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,6,20]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1199\/tab.0018"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8295-8"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00182"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710791556023"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611796575911"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/156802611796575948"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-2-48"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/9376"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990664p"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm900267n"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2011.11.034"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300662d"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501416t"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301893b"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00926"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01881"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm501416t"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201601679"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2013.02.016"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2012.04.012"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.2c00546"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700293"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.07.044"},{"key":"e_1_2_8_24_1","author":"Sk\u00e1cel J.","year":"2023","journal-title":"J. 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