Synthesis and antiviral activity of carbocyclic analogues of xylofuranosides of 2-amino-6-substituted-purines and 2-amino-6-substituted-8-azapurines.
(+/-)-(1 alpha,2 beta,3 alpha,5 alpha)-3-[(2,5-Diamino-6-chloro-4- pyrimidinyl)amino]-5-(hydroxymethyl)-1,2-cyclopentanediol (7) was synthesized from 2-amino-4,6-dichloropyrimidine and the carbocyclic xylofuranosylamine (+/-)-(1 alpha,2 beta,3 alpha,5 alpha)-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. Analogue 9 also exhibited potent activity against human cytomegalovirus and varicella-zoster virus.
Vince
R
R
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.
Turakhia
R H
RH
Shannon
W M
WM
Arnett
G
G
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D007941:Leukemia P388 / Q000473:pathology; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects
D000998:Antiviral Agents; D011687:Purines