Synthesis, bioactivation and anti-HIV activity of 4-acyloxybenzyl bis(nucleosid-5'-yl) phosphates

Article abstract of DOI:10.1080/15257779508009491

4-Acyloxybenzyl bis(nucleosid-5'-yl) phosphates 7a-c and 9a-c were prepared as potential prodrugs of the anti-HIV nucleosides 3'-azido-3'- deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI) or their 5'- monophosphates. The anti-HIV activities of these triesters were determined in two T-cell lines. In a C8166 cell line they displayed activities comparable to and in some cases superior to AZT, but they also exhibited an increase in cytotoxicity. In a thymidine kinase deficient JM T-cell line the activity was reduced but was still superior to AZT. In the presence of porcine liver carboxyesterase (PLCE), triester 7b biodegrades to the diester 10 which, with phosphodiesterase, gives initially AZT monophosphate 3 and AZT.

Full text of DOI:10.1080/15257779508009491

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Synthesis, Bioactivation and Anti-
HIV Activity of 4-Acyloxybenzyl
bis(Nucleosid-5′-yl) Phosphates
Anne Routledge a d , Ian Walker a , Sally Freeman a e , Alan Hay b &
Naheed Mahmood c
a Department of Pharmaceutical and Biological Sciences , Aston
University , Aston Triangle, Birmingham, B4 7ET, U.K.
b National Institute for Medical Research , The Ridgeway, Mill Hill,
London, NW7 1AA, U.K.
c MRC Collaborative Centre , 1-3 Burtonhole Lane, Mill Hill, London,
NW7 1AD, U.K.
d Department of Chemistry , University of Cambridge , Lensfield Rd,
Cambridge, CB2 1EW, U.K.
e Department of Pharmacy , University of Manchester , Manchester,
M13 9PL, U.K.
Published online: 24 Sep 2006.
To cite this article: Anne Routledge , Ian Walker , Sally Freeman , Alan Hay & Naheed Mahmood
(1995) Synthesis, Bioactivation and Anti-HIV Activity of 4-Acyloxybenzyl bis(Nucleosid-5′-yl)
Phosphates, Nucleosides and Nucleotides, 14:7, 1545-1558
To link to this article: http://dx.doi.org/10.1080/15257779508009491
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