Studies of N-hydroxy-N'-aminoguanidine derivatives by nitrogen-15 nuclear magnetic resonance spectroscopy and as ribonucleotide reductase inhibitors

Hydroxyguanidine, with the imino group of guanidine and the hydroxyamino group of hydroxyurea, has functional groups believed to be important for both anticancer and antiviral activities (Adamson, R.H. Nature (London) 1972, 236, 400-401). Three new N-hydroxy-N'-aminoguanidine derivatives have been synthesized and found to be 20-30 times more active than the hydroxyguanidine itself as inhibitors of ribonucleotide reductase from rat Novikoff tumors (Tai, W.A.; Lai, M.M.; Lien, E.J. "Novel N-Hydroxyguanidine Derivatives as Antiviral Agents", North American Medicinal Chemistry Symposium, University of Toronto, Toronto, Canada, June 20-24, 1982; Abstr, p 144). The character of the tautomeric equilibria, the pKa values, and the protonation sites of these hydroxyguanidine derivatives have been determined by 15N NMR spectroscopy.