Purine acyclic nucleosides. Nitrogen isosteres of 9-[(2-hydroxyethoxy)methyl]guanine as candidate antivirals.
A number of nitrogen analogues of 9-[(2-hydroxyethoxy)methyl]guanine [acylovir, Zovirax] containing amine functions in the side chain were synthesized and tested for antiviral activity. These purine acyclic nucleosides were prepared by reaction of tris(trimethylsilyl)guanine or 2,6-diaminopurine sodium salt with the chloromethyl ethers prepared from N-(2-hydroxyethyl)phthalimide, N-[2-(2-hydroxyethoxy)ethyl]phthalimide, or N-(2-hydroxyethyl)oxazolidin-2-one to give the N-blocked intermediates 5-8. Deprotection with hydrazine or by alkaline hydrolysis gave 9-[(2-aminoethoxy)methyl]guanine (9), 9-[(2-aminoethoxy)methyl]-2,6-diaminopurine (10), 9-[2(2-aminoethoxy]ethoxymethyl]guanine (11), and 9-[[2-[(2-hydroxyethyl)amino]ethoxy]methyl]guanine (12). When tested against herpes simplex virus type 1, only 9 was active with an IC50 = 8 microM. Little or no activity was observed against a range of other DNA and RNA viruses.
D000212:Acyclovir / Q000031:analogs & derivatives*; D000998:Antiviral Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; D006147:Guanine; C017549:9-((2-aminoethoxy)methyl)guanine; D000212:Acyclovir