Aryl H-Phosphonates 17: (N-Aryl)phosphoramidates of Pyrimidine Nucleoside Analogues and Their Synthesis, Selected Properties, and Anti-HIV Activity
| Autor: | Aleksandra Dąbrowska, Adam Kraszewski, Zofia M. Pietrusiewicz, Joanna Romanowska, Andrzej Guranowski, Marek Figlerowicz, Krystian Kolodziej, Andrzej Piasek, Jerzy Boryski, Jacek Stawinski, Andrzej Lipniacki, Michal Sobkowski, Agnieszka Szymanska-Michalak |
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| Rok vydání: | 2011 |
| Předmět: |
Anti hiv activity
Pyrimidine Anti-HIV Agents Chemistry Stereochemistry Aryl Organophosphonates Phosphoramidate Pyrimidine Nucleosides HIV Reverse Transcriptase Structure-Activity Relationship chemistry.chemical_compound Drug Discovery HIV-1 Humans Reverse Transcriptase Inhibitors Molecular Medicine Hydrophobic and Hydrophilic Interactions Nucleoside Cells Cultured |
| Zdroj: | Journal of Medicinal Chemistry. 54:6482-6491 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm2001103 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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