Synthesis and antiviral activity of a series of 1′-substituted 4-aza-7,9-dideazaadenosine C-nucleosides

Abstract

A series of 1'-substituted analogs of 4-aza-7,9-dideazaadenosine C-nucleoside were prepared and evaluated for the potential as antiviral agents. These compounds showed a broad range of inhibitory activity against various RNA viruses. In particular, the whole cell potency against HCV when R=CN was attributed to inhibition of HCV NS5B polymerase and intracellular concentration of the corresponding nucleoside triphosphate.

Antioxidant and Antitumor Activities of New Synthesized Aromatic C-Nucleoside Derivatives

“…Their structures were confirmed by IR, 1 H-NMR, two dimentional 1 H-NMR (COSY), 13 C-NMR and mass spectral data. The 1 H-NMR spectrum (DMSO-d 6 ) of compound 3c, for example, showed five singlets around δ 11.94, 11.14, 8.13, 6.83 and 6.74, supporting the presence of NH (1) , NH (2) (D 2 O exchangeable), azomethine (CH=N), CH (pyrrole) and CH (furan) protons, respectively. Signals of the sugar protons of these derivatives 3a-e were assigned from the 2D 1 H-NMR spectrum of compound 3c, and the characteristic chemical shifts as compared with those reported for carbohydrazones [1], whereby, four doublets appearing at δ 5.14, 4.75, 4.60, 4.46 ppm were assigned to 1'-OH, H-1', 2'-OH and 3'-OH, respectively, and a triplet at δ (4.35) ppm for 4'-OH.…”

“…In addition the 1 H-NMR spectrum (DMSO-d 6 ) of this product, showed a high field singlet at δ 9.60 ppm for the aldehyde proton (CHO). The mass spectrum showed the molecular ion peak at m/z 297 (M + , 22.54%).…”

“…Then it was poured onto crushed ice, the acetyl derivative that separated out, was filtered off, washed with water and dried. (5 (6). Obtained in 100% yield from compound 3e; recrystallized from ethanol as yellow needles; mp 154-155 °C; Rf: 0.54 (n-hexane-ethyl acetate; 5:1; v/v); IR (KBr) cm (7).…”

“…Moreover, dehydrative cyclization of the tetraol derivative 8 with aqueous acetic acid (10%) afforded the aromatic C-nucleoside 9 in 63% yield, as detected from its spectral data. Its 1 H-NMR spectrum (DMSO-d 6 ) showed only two D 2 O-exchangeable hydroxyl protons for 2'-OH and 3'-OH, as two doublets at δ 5.16 and 5.03 ppm, respectively. The mass spectrum showed the expected molecular ion peak in agreement with its structure.…”

“…A number of nucleoside analogues have been found to show a broad spectrum of biological effects such as antifungal [1,2], antibacterial [1][2][3], antitumor [3][4][5], antiviral [3,4,[6][7][8][9][10][11][12][13][14] anti-inflammatory [15] and analgesic [15] activities. Moreover, 2'-deoxy-2'-fluoro-2'-C-methyl nucleoside analogues have showed promising activity against HCV replication [16].…”