Synthesis and antiviral activity of carbocyclic analogues of 2'-deoxyribofuranosides of 2-amino-6-substituted-purines and of 2-amino-6-substituted-8-azapurines.
(+/-)-(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 analogue of 2-amino-6-chloropurine 2'-deoxyribofuranoside (10) was prepared from 9 and triethyl orthoformate, and the analogous 8-azapurine (11) was obtained by diazotizing 9. From 10 or 11, the carbocyclic analogues of 2'-deoxyguanosine, 2'-deoxythioguanosine, 2,6-diaminopurine 2'-deoxyribofuranoside, 2'-deoxy-8-azaguanosine, and 2,6-diamino-8-azapurine 2'-deoxyribofuranoside were prepared. All of these 2'-deoxyribofuranoside analogues were active against herpes simplex virus (types 1 and 2) replicating in cells in culture; some demonstrated potent activity.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011684:Purine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; D003853:Deoxyribonucleosides; D011684:Purine Nucleosides; D011687:Purines; C015008:triazolopyrimidinone