Design and SAR study of a novel class of nucleotide analogues as potent anti-HCMV agents.
We have developed a novel class of 2-phosphonate 1,3-dioxolane nucleotide analogues, from which the guanine derivative displayed weak anti-HCMV activity. Further SAR studies led to the identification of both cis and trans guanine derivatives of tetrahydrofuran analogues as potent anti-HCMV agents, both in vitro and in vivo, compared to ganciclovir and HPMPC.
Nguyen-Ba
N
N
BioChem Therapeutic Inc., Laval, Québec, Canada.
Chan
L
L
Quimpère
M
M
Turcotte
N
N
Lee
N
N
Mitchell
H
H
Bédard
J
J
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D000077404:Cidofovir; D003587:Cytomegalovirus / Q000187:drug effects*; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000494:pharmacology; D006150:Guanine Nucleotides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D006150:Guanine Nucleotides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir