Effect of acyclic pyrimidines related to 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine on herpesviruses.
A series of pyrimidines related to the potent antiherpetic agent 9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (1, BW B759U), all containing the same acyclic chain, have been synthesized. Some of the compounds were derivatives of the naturally occurring bases, cytosine, uracil, and thymine; others included compounds in which the 5-position of the cytosine and uracil moieties were substituted by bromo, iodo, fluoro, methyl, and amino groups. Other variations of the cytosine derivatives were the 5-aza, 2-mercapto, 4-methylamino, 4-dimethylamino, and isocytosine congeners. A 4-aminopyrimidine adduct was also made. Antiviral testing showed that 1-[(1,3-dihydroxy-2-propoxy)methyl]cytosine (18, BW A1117U) was equivalent to the guanine analogue in potency against human cytomegalovirus and Epstein Barr virus. Other compounds in the series were largely inactive in antiviral screening against the herpesviruses.
Beauchamp
L M
LM
Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
Serling
B L
BL
Kelsey
J E
JE
Biron
K K
KK
Collins
P
P
Selway
J
J
Lin
J C
JC
Schaeffer
H J
HJ
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis*; D002460:Cell Line; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects* / Q000235:genetics; D005814:Genes, Viral / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D007202:Indicators and Reagents; D011743:Pyrimidines; D000212:Acyclovir