Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1392647 | European Journal of Medicinal Chemistry | 2013 | 8 Pages |
•Phosphoramidates of 3′-azido-2′,3′-dideoxy-5-fluorouridine were synthesized.•Obtained phosphoramidates were evaluated for their cytotoxic activity.•The highest activity was displayed by phosphoramidate with the N-ethyl substituent.•Phosphoramidate with N-propargyl substituent exhibited also fairly high activity.
A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3′-azido-2′,3′-dideoxy-5-fluorouridine (12–21) were synthesized by means of phosphorylation of 3′-azido-2′,3′-dideoxy-5-fluorouridine (4) with 4-chlorophenyl phosphoroditriazolide (10) followed by a reaction with the appropriate amine. The synthesized phosphoramidates (12–21) were evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7) using the sulforhodamine B (SRB) assay. The highest activity in all the investigated cancer cells was displayed by phosphoramidate 13 with the N-ethyl substituent and its activity was much higher than that of the parent nucleoside. Also phosphoramidate 17 with the N-propargyl substituent exhibited good activity in all the used cell lines.
Graphical abstractA series of 4-chlorophenyloxy N-alkyl phosphoramidates of 3′-azido-2′,3′-dideoxy-5-fluorouridine were synthesized and evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).Figure optionsDownload full-size imageDownload as PowerPoint slide