Synthesis and Antiviral Evaluation of Carboxylic Analogues of 2-Amino-6-substituted-purine 3'-Deoxyribofuranosides

Article abstract of DOI:10.1021/jm00389a019

Carbocyclic analogues of 2-amino-6-substituted-purine 3'-deoxyribofuranosides were synthesized by beginning with (+/-)-(1α,3α,4β)-3-amino-4-hydroxycyclopentanemethanol and 2-amino-4,6-dichloropyrimidine.The route parallels the earlier syntheses of the corresponding ribofuranoside and 2'-deoxyribofuranoside analogues.The 2-amino-6-chloropurine, guanine, and 2,6-diaminopurine derivatives and the analogous 8-azapurines were prepared.The analogue (3'-CDG) of 3'-deoxyguanosine is active in vitro against a strain of type 1 herpes simplex virus (HSV-1) that induces thymidine kinase and is modestly active against a thymidine kinase inducing strain of type 2-HSV. 3'-CDG is not active against a strain of HSV-1 that lacks the thymidine kinase inducing capacity, whereas the carbocyclic analogue of 2 amino-6-chloropurine 3'-deoxyribofuranoside is active against that strain.The carbocyclic analogue of 2,6-diaminopurine 3'-deoxyribofuranoside displayed modest activity in vitro against influenza virus.