(D)- and (L)-cyclohexenyl-G, a new class of antiviral agents: synthesis, conformational analysis, molecular modeling, and biological activity.
(D)- and (L)-cyclohexeneyl-G were synthesized enantioselectively starting from (R)-carvone. Both show potent and selective anti-herpesvirus activity (HSV-1, HSV-2, VZV, CMV). Molecular modeling demonstrates that both isomers are bound in the active site of HSV-1 thymidine kinase in a high-energy conformation with the base moiety orienting in an equatorial position. It is believed that the flexibility of the cyclohexene ring is essential for their antiviral activity.
Wang
J
J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
Froeyen
M
M
Hendrix
C
C
Andrei
C
C
Snoeck
R
R
Lescrinier
E
E
De Clercq
E
E
Herdewijn
P
P
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000081005:Cyclohexane Monoterpenes; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053138:Cyclohexenes; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006564:Herpesviridae / Q000187:drug effects / Q000201:enzymology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D039821:Monoterpenes; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry; D013937:Thymidine Kinase / Q000378:metabolism
D000998:Antiviral Agents; D000081005:Cyclohexane Monoterpenes; D003510:Cyclohexanes; D053138:Cyclohexenes; D039821:Monoterpenes; D013729:Terpenes; C442681:cyclohexenyl-G; C052568:cyclohexene; D006147:Guanine; C006923:carvone; D013937:Thymidine Kinase