1990
DOI: 10.1177/095632029000100603
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Synthesis and anti-HIV Activity of Some Novel Substituted Dialkyl Phosphate Derivatives of AZT and ddCyd

Abstract: The reaction of thymidine, AZT (Fig. 1, compound 1) and ddCyd (Fig. 1, compound 2) with bis(2,2,2-trichloroethyl) phosphorochloridate gave novel 5 '_ bis(2,2,2-trichloroethyl) phosphates, characterized by spectroscopic and analytical data. Analogous reactions with bis(2,2,2-trifluoroethyl) phosphorochloridate gave the corresponding AZT and ddCyd derivatives. In both of the ddCyd reactions, by-products were isolated and characterized as 05', N4-diphosphorylated materials. It was hoped that the 5 '_ phosphate tr… Show more

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Cited by 39 publications
(23 citation statements)
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“…Thus, simple dialkyl phosphate derivatives of AZT are extremely resistant to phosphate hydrolysis, and they display no antiviral effect [3]. On the other hand bis(trihaloethy1) phosphate derivatives of zidovudine and of 2',3'-dideoxycytidine (ddC) show significant lability towards hydrolysis [ 191, and are potent inhibitors of viral proliferation [5]. We have also noted that one of these phosphate masking groups, the bis(2,2,2-trichloroethyl) phosphate moiety is successful in the kinase by-pass activation of certain inactive 3'-modified nucleosides [l l-121.…”
Section: Resultsmentioning
confidence: 99%
“…Thus, simple dialkyl phosphate derivatives of AZT are extremely resistant to phosphate hydrolysis, and they display no antiviral effect [3]. On the other hand bis(trihaloethy1) phosphate derivatives of zidovudine and of 2',3'-dideoxycytidine (ddC) show significant lability towards hydrolysis [ 191, and are potent inhibitors of viral proliferation [5]. We have also noted that one of these phosphate masking groups, the bis(2,2,2-trichloroethyl) phosphate moiety is successful in the kinase by-pass activation of certain inactive 3'-modified nucleosides [l l-121.…”
Section: Resultsmentioning
confidence: 99%
“…General synthetic procedures were similar to those we have described [5]. Full details are given for compound (3b); subsequent compounds were similarly prepared and characterised.…”
Section: Chemistrymentioning
confidence: 99%
“…Given our experience in the improvement of the therapeutic performance of bio-active nucleosides by suitable phosphate modification [8,9,10,11,12] we wondered if a similar strategy might lead to enhancement of the properties of the parent ALP. *Corresponding author.…”
Section: Introductionmentioning
confidence: 99%