Novel non-nucleoside human cytomegalovirus inhibitors based upon TSAO nucleoside derivatives: structure-activity relationships.
TSAO derivatives are a unique group of potent and highly specific inhibitors of HIV-1 replication. We have recently reported 4''-ureido TSAO derivatives that are devoid of anti-HIV-1 activity, but inhibit human cytomegalovirus with an activity comparable to that of Ganciclovir. We herein report the synthesis and biological evaluation of novel 4''-ureido TSAO derivatives in order to evaluate the structural features required for anti-HCMV activity. Interestingly, these studies revealed that the compounds may inhibit HCMV at the DNA polymerase step via a non-nucleoside mechanism.
de Castro
Sonia
S
Instituto de Química Médica (CSIC), Madrid, Spain.
Andrei
Graziela
G
Snoeck
Robert
R
Balzarini
Jan
J
Camarasa
María-José
MJ
Velázquez
Sonsoles
S
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009705:Nucleosides / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D009705:Nucleosides; D013141:Spiro Compounds