Synthesis and antiviral activity of carbocyclic analogs of 2'-deoxyribofuranosides of 2-amino-6-substituted-purines and of 2-amino-6-substituted-8-azapurines

Abstract

(.+-.)-(1.alpha.,2.beta.,4.alpha.)-4-[(2,5-Diamino-6-chloro-4-pyrimidinyl)amino]-2-hydroxycyclopentanemethanol (9) was synthesized by beginning with 2-amino-4,6-dichloropyrimidine and (.+-.)-(1.alpha.,2.beta.,4.alpha.)-4-amino-2-hydroxycyclopentanemethanol, preparing the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine and reducing the azo derivative. The carbocyclic analog of 2-amino-6-chloropurine 2''-deoxyribofuranoside (10) was prepared from 9 and triethyl orthoformate, and the analgous 8-azapurine (11) was obtained by diazotizing 9. From 10 or 11, the carbocyclic analogs of 2''-deoxyguanosine, 2''-deoxythioguanosine, 2,6-diaminopurine 2''-deoxyribofuranoside, 2''-deoxy-8-azaquanosine and 2,6-diamino-8-azapurine 2''-deoxyribofuranoside were prepared. All of these 2''-deoxyribofuranoside analogs were active against herpes simplex virus (types 1 and 2) replicating in cells in culture; some demonstrated potent activity.