Side-Chain Derivatives of Biologically Active Nucleosides. Part 2: Synthesis and anti-HIV Activity of 5′-C-Methyl Derivatives of 3′-Fluoro-3′-Deoxythymidine

Abstract

1-(3′-Fluoro-2′,3′,6′-trideoxy-β-D-allofuranosyl)thymine [7] and 1-(3′-fluoro-2′,3′,6′-trideoxy-α-L-talofuranosyl) thymine [8] were synthesized starting from the corresponding 2,3′-anhydro nucleoside derivatives. The fluorine was introduced stereoselectively by opening of the anhydro bridge in the presence of HF/AIF3. The 5′-C-methyl derivatives, [7] and [8], of 3′-fluoro-3′-deoxythymidine (FLT) were evaluated for their inhibitory effect against human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The compounds [7] and [8] had antiviral activity which was three orders of magnitude lower than the reference compound 3′-fluoro-3′-deoxythymidine. None of the compounds showed appreciable activity against other RNA or DNA viruses at subtoxic concentrations.

Activated nitriles in heterocyclic synthesis: Facile synthesis of heteroarylthymine analogs and their nucleosides

“…Furthermore, thymines and their substituted derivatives were prepared to investigate their biological behavior (e.g., anticancer and antiviral properties) [4][5][6]. In the present work, we aimed at preparing heteroaryl analogs of thymines, as well as their nucleosides, starting with N-cyanoacetylurea (1).…”

Synthesis and structure of novel phosphonodipeptides containing a uracil or thymine group

“…Various uracil and thymine derivatives have been synthesized and tested as anticancer or antivi- ral drugs [13][14][15][16][17]. Pyrimidin-1-yl or purin-9-yl phosphonic acids were also found to be a new class of antiviral agents with a broad spectrum of activities against retroviruses and DNA virus for inhibiting DNA polymerase [18][19].…”