The journey towards elucidating the anti-HCMV activity of alkylated bicyclic furano pyrimidines.
Bicyclic furanopyrimidines were recently discovered by us to be potent and selective inhibitors of VZV. Related studies to investigate the role of the sugar in this activity uncovered dideoxy furanopyrimidines as inhibitors of HCMV and this led to the preparation of highly modified long alkyl chain furanopyrimidines from the N- and O-alkylation of their parent bases. Herein we describe their synthesis and subsequent biological evaluation against HCMV. O-alkylated derivatives were almost invariably found to be at least equiactive with their N-alkylated counterparts. At this point, little change in activity has been found with large variation in N- and O-substituent.
Kelleher
M R
MR
Welsh School of Pharmacy, Cardiff University, Redwood Building, Edward VI Ave., CF10 3XF, Cardiff, UK. kellehermr@cf.ac.uk
McGuigan
C
C
Bidet
O
O
Carangio
A
A
Weldon
H
H
Andrei
G
G
Snoeck
R
R
De Clercq
E
E
Balzarini
J
J
D000998:Antiviral Agents / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003587:Cytomegalovirus / Q000378:metabolism*; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D015195:Drug Design; D005663:Furans / Q000737:chemistry*; D006801:Humans; D008956:Models, Chemical; D010766:Phosphorylation; D011741:Pyrimidine Nucleosides / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry*
D000998:Antiviral Agents; D005663:Furans; D011741:Pyrimidine Nucleosides; D011743:Pyrimidines