title: Aryl H-Phosphonates 18. Synthesis, properties, and biological activity of 2',3'-dideoxynucleoside (N-heteroaryl)phosphoramidates of increased lipophilicity.
abstract: Recently, AZT (N-pyridyl)phosphoramidates were reported as a new type of potential anti-HIV therapeutics. In continuation of that work, here we present new (N-heteroaryl)phosphoramidate derivatives of antiviral 2',3'-dideoxynucleosides containing other types of N-heteroaryl moieties, particularly those with higher lipophilicity. The present studies comprise mechanistic investigations using (31)P NMR correlation analysis, which permitted improvements in the synthetic procedures. The obtained compounds were tested in biological systems to establish their cytotoxicity and anti-HIV activity. The results were analyzed with respect to possible correlations between biological and physico-chemical properties of the phosphoramidates studied, to get some insight into their antiviral mode of action.
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Krystian
authors.initials: K
authors.lastname: Kolodziej
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Romanowska
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Stawinski
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Boryski
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dabrowska
authors.affiliation: National Institute of Medicines, Chełmska 30/34, 00-725 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lipniacki
authors.affiliation: National Institute of Medicines, Chełmska 30/34, 00-725 Warsaw, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Piasek
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland. Electronic address: Adam.Kraszewski@ibch.poznan.pl.
authors.forename: Adam
authors.initials: A
authors.lastname: Kraszewski
authors.affiliation: Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznań, Poland. Electronic address: msob@ibch.poznan.pl.
authors.forename: Michal
authors.initials: M
authors.lastname: Sobkowski
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D015224:Dideoxynucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides
keywords: 2′,3′-dideoxynucleosides; AZT; Anti-HIV; H-phosphonates; Heteroaryl amines; Lipophilicity; Phosphoramidates; Pro-nucleotides