Synthesis and antiviral activity of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine.
A number of methyl derivatives of 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG, 1) have been synthesized and tested in vitro for anti-herpes and anti-human immunodeficiency virus (HIV) activity. Among these analogues, (R)-2'-methyl-PMEG [(R)-3] and 2',2'-dimethyl-PMEG (7) demonstrated potent anti-HIV activity in the XTT assay with EC50 values of 1.0 and 2.6 microM, respectively. The corresponding (S)-2'-methyl-PMEG [(S)-3] was found to be less potent against HIV. In addition, the (R) and (S) enantiomers of 9-[3-hydroxy-2-(phosphonomethoxy)propyl]guanine (HPMPG, 8) were prepared for comparison of biological activity, and shown to be active and equipotent against herpesviruses, but inactive against HIV.
Yu
K L
KL
Bristol-Myers Squibb Company, Pharmaceutical Research Institute, Wallingford, Connecticut 06492-7660.
Bronson
J J
JJ
Yang
H
H
Patick
A
A
Alam
M
M
Brankovan
V
V
Datema
R
R
Hitchcock
M J
MJ
Martin
J C
JC
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D006678:HIV / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D018139:Simplexvirus / Q000187:drug effects; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D009943:Organophosphorus Compounds; C063380:9-((2-phosphonylmethoxy)ethyl)guanine; D006147:Guanine