title: Aryl H-phosphonates 17: (N-aryl)phosphoramidates of pyrimidine nucleoside analogues and their synthesis, selected properties, and anti-HIV activity.
abstract: New synthetic protocol for the preparation of nucleoside 5'-(N-aryl)phosphoramidate monoesters 4 was developed. It consisted of a condensation of the corresponding nucleoside 5'-H-phosphonates with aromatic- or heteroaromatic amines promoted by diphenyl phosphorochloridate, followed by oxidation of the produced H-phosphonamidates with iodine/water. 5'-(N-Aryl)phosphoramidate monoesters derived from 3'-azido-3'-deoxythymidine (AZT) or 2',3'-dideoxyuridine (ddU) nucleosides and various aromatic and heteroaromatic amines were evaluated as potential anti-HIV drugs. It was found that these compounds act most likely as pronucleotides and that some of them have therapeutic indices superior to those of the reference AZT.
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.forename: Michał
authors.initials: M
authors.lastname: Sobkowski
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Szymańska-Michalak
authors.forename: Krystian
authors.initials: K
authors.lastname: Kołodziej
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Dąbrowska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Lipniacki
authors.forename: Andrzej
authors.initials: A
authors.lastname: Piasek
authors.forename: Zofia M
authors.initials: ZM
authors.lastname: Pietrusiewicz
authors.forename: Marek
authors.initials: M
authors.lastname: Figlerowicz
authors.forename: Andrzej
authors.initials: A
authors.lastname: Guranowski
authors.forename: Jerzy
authors.initials: J
authors.lastname: Boryski
authors.forename: Jacek
authors.initials: J
authors.lastname: Stawiński
authors.forename: Adam
authors.initials: A
authors.lastname: Kraszewski
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D011741:Pyrimidine Nucleosides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase