Pyrimidine acyclic nucleosides, 1-[(2-Hydroxyethoxy)methyl]pyrimidines as candidate antivirals.
A number of pyrimidine acyclic nucleosides were synthesized and tested for activity against herpes simplex virus type 1. Synthesis of 1-[(2-hydroxyethoxy)methyl]cytosine (8) and 1-[(2-hydroxyethoxy)methyl]uracil (14) was accomplished in two or three steps from 2,4-diethoxypyrimidine and 2-(benzoyloxy)ethoxymethyl chloride. The 5-methyl (20), 5-(trifluoromethyl) (21), and 5-fluoro (22) analogues of 14 were available in two steps form the appropriate bis(trimethylsilyl)ated 5-substituted uracil and 2-(acetoxymethoxy)ethyl acetate or 2-(benzoyloxy)ethoxymethyl chloride. Bromination of 8 and 14 or iodination of 14 gave the 5-halogeno-1-[(2-hydroxyethoxy)methyl]pyrimidines 9, 23, and 24. These pyrimidine acyclic nucleosides exhibited little or no activity against herpes simplex virus type 1 or against a range of other DNA and RNA viruses. This is compatible with their lack of substrate properties toward herpes simplex virus induced thymidine kinase.
D000212:Acyclovir; D000818:Animals; D000998:Antiviral Agents; D004267:DNA Viruses / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects; D018139:Simplexvirus / Q000187:drug effects*; D014498:Uracil / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides; D014498:Uracil; D006147:Guanine; D000212:Acyclovir