Synthesis and characterization of 2′-C-Me branched C-nucleosides as HCV polymerase inhibitors

Discovery and Synthesis of C-Nucleosides as Potential New Anti-HCV Agents

“…Convergent methods for 1 and 2 have also been reported by others since we completed this work. 12 Guanosine analogues 4 and 5 were prepared using an analogous approach, as shown in Scheme 3. Compounds 21 and 26 were chosen as appropriate starting heterocycles.…”

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

“…(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). A solution of compound 5 (5.523 mmol) in dry ether (75 mL) was stirred with yellow mercuric oxide (4.80 g), magnesium oxide (0.48 g), and iodine (4.00 g) at room temperature for 48 h under anhydrous conditions.…”

“…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].…”

Nucleosides and Nucleotides for the Treatment of Viral Diseases

“…To investigate the potential for C-nucleosides as inhibitors of HCV replication, several reports have investigated both purine and pyrimidine C-nucleoside derivatives (49)(50)(51)(52)(53)(54)(55). 62 Despite a favorable in vitro toxicity profile, adverse events, including death, were observed when 50 was dosed orally in rats. Only the adenosine analogs 49 (EC 50 ¼ 1.28 μM) and 50 (EC 50 ¼ 1.98 μM) demonstrated inhibition of HCV replication with their corresponding triphosphates showing inhibition of the viral polymerase.…”

“…Investigation of a series of 2 0 -spironucleosides bearing either a 2 0 -oxetane or 2 0 -tetrahydrofuran moiety (62) identified several oxetanes as inhibitors of the HCV polymerase but only weakly active as inhibitors of HCV replication in the replicon assay. 69,70 Subsequent preparation of phosphoramidate nucleotide prodrug variants (63) resulted in increased whole cell potency.…”