Structure-activity studies on phosphonoacetate.
Phosphonoacetic acid is a selective antiherpesvirus agent. More than 100 congeners of phosphonoacetic acid were evaluated in vitro and in vivo to understand structure-activity relationships in the hope of designing a superior analog. Results showed that the antiherpesvirus activity had highly specific structural requirements. Neither the carboxylic nor the phosphono groups could be replaced. The distance between these two groups is important. Increase of this distance caused complete loss of activity. However, if this distance was maintained, the addition of groups to the methylene carbon resulted in a reduction, but not loss, of activity. On the other hand, decrease of the carbon chain to formic acid did not deteriorate its antiherpes activity. All analogs tested had lower activity than the parent compound. However, some compounds with decreased activity in vitro appeared to have favorable pharmacological properties in vivo.
Mao
J C
JC
Otis
E R
ER
von Esch
A M
AM
Herrin
T R
TR
Fairgrieve
J S
JS
Shipkowitz
N L
NL
Duff
R G
RG
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D046508:Culture Techniques; D003872:Dermatitis / Q000188:drug therapy / Q000209:etiology; D004352:Drug Resistance, Microbial; D006561:Herpes Simplex / Q000188:drug therapy; D006801:Humans; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship
D000596:Amino Acids; D019384:Nucleic Acid Synthesis Inhibitors; D009943:Organophosphorus Compounds; D010746:Phosphonoacetic Acid