Synthesis and antiviral activity of carbocyclic analogues of xylofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines

Article abstract of DOI:10.1021/jm00394a017

(±)-(1α,2β,3α,5α)-3-[(2,5-Diamino-6-chloro-4-pyrimidinyl)amino] -5-(hydroxmethyl)-1,2-cyclopentanediol (7) was synthesized from 2-amino-4,6-dichloropyrimidine and the carbocyclic xylofuranosylamine (±)-(1α,2β,3α,5α)-3-amino-5-(hydroxymethyl)-1,2-cyclopentanediol (2) by subsequent preparation of the 5-[(4-chlorophenyl)azo] derivative of the resulting pyrimidine and reduction of the azo moiety with zinc and acetic acid. The carbocyclic analogue of 2-amino-4-chloropurine xylofuranoside (8) and the corresponding 8-azapurine 11 were prepared from 7. The carbocyclic analogues xylofuranosylguanine (9), xylofuranosyl-2,6-diaminopurine (10), xylofuranosyl-8-azaguanine (13), and xylofuranosyl-8-aza-2,6-diaminopurine (14) were prepared from 8 and 11. Compounds 9 and 13 were active against herpes simplex virus (types 1 and 2), with 9 being the more potent against both viruses. Analogues 9 also exhibited potent activity against human cytomegalovirus and varicella-zoster virus.