Preparation and Anti-HIV Activity of N-3-Substituted Thymidine Nucleoside Analogs
- 1 May 1997
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 40 (10) , 1550-1558
- https://doi.org/10.1021/jm9600095
Abstract
A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045−0.082 μM range. The analogs 12d, 12e, 12q, 15, and 19 were active at (12-18)] and poly(C)-oligo[dG(12-18)] template−primers. In contrast to AZT−TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequisite for activity.Keywords
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