Purine acyclic nucleosides. Nitrogen isosteres of 9-[(2-hydroxyethoxy)methyl]guanine as candidate antivirals

Article abstract of DOI:10.1021/jm00144a033

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. Deprotection with hydrazine or by alkaline hydrolysis gave 9-[(2-aminoethoxy)methyl]guanine(A), 9-[(2-aminoethoxy)methyl]-2,6-diaminopurine, 9-[[2-(2-aminoethoxy)ethoxy]methyl]guanine, and 9-[[2-[(2-hydroxyethyl)amino]ethoxy]methyl]guanine. When tested against herpes simplex virus type 1, only (A) was active with an IC₅₀ = 8 μM. Little or no activity was observed against a range of other DNA and RNA viruses.