Synthesis and antiviral and antimicrobial activity of certain 1-beta-D-ribofuranosyl-4,5-disubstituted imidazoles.
Starting with AICA ribonucleoside the following nucleosides were prepared. Methyl 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (5) was converted into methyl 5-chloro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carboxylate (6) via diazotization in the presence of cuprous chloride. Similarly, 5-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuanosyl)imidazole-4-carbonitrile (9) was converted into 5-chloro-, 5-bromo-, and 5-iodo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile derivatives. These 5-halogenated imidazole nucleosides were treated with several nucleophiles such as ammonia, hydroxylamine, and hydrogen sulfide to provide, respectively, 5-haloimidazole-4-carboxamide, 5-haloimidazole-4-carboxamidoxime, and 5-haloimidazole-4-thiocarboxamide ribonucleosides. 5-Chloro- or 5-bromo-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)imidazole-4-carbonitrile was treated with potassium hydrosulfide to yield 5-mercapto-1-beta-D-ribofuranosylimidazole-4-thiocarboxamide (16). The catalytic reduction of 5-chloro- or 5-bromo-1-beta-D-ribofuranosylimidazole-4-carboxamidoxime provided 1-beta-D-ribofuranosylimidazole-4-carboxamidines as their hydrochloride and hydrobromide salts, respectively. These nucleosides were tested for in vitro antiviral, antifungal, and antibacterial activity. The 5-halo analogues of 1-beta-D-ribofuranosylimidazole-4-carboxamide showed significant antiviral activity whereas compound 16 was found inhibitory to fungi.
D000227:Adenine Nucleotides / Q000096:biosynthesis; D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis*; D000935:Antifungal Agents / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006150:Guanine Nucleotides / Q000096:biosynthesis; D006168:Guinea Pigs; D006564:Herpesviridae / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects; D012229:Rhinovirus / Q000187:drug effects; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014005:Tinea / Q000188:drug therapy; D014616:Vaccinia virus / Q000187:drug effects
D000227:Adenine Nucleotides; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000998:Antiviral Agents; D006150:Guanine Nucleotides; D007093:Imidazoles; D012263:Ribonucleosides