Bioisosters of the diphosphate group in activated forms of antiherpes virus agents. A theoretical study.
In order to identify potential bioisosteric replacements for the diphosphate moiety, which is present in activated forms generated from antiherpes virus agents during their inhibitory action against herpes viruses, 5'-phosphonoacetamido (4) and 5'-O-sulfamoylcarbamoyl (5) derivatives of idoxuridine were synthesised as analogues of idoxuridine 5'-diphosphate (6). In this paper we report on the antiherpetic activity of 4 and 5. Moreover, a theoretical study is presented in which both the conformational and the electronic characteristics of 4 and 5 are compared with those of the diphosphate metabolite of idoxuridine (6), in order to verify the possibility of bioisosterism relationship between the phosphonoacetamido, the sulfamoylcarbamoyl and the diphosphate group.
Macchia
M
M
Istituto di Chimica Farmaceutica e Tossicologica, Università di Pisa, Italy.
Martinelli
A
A
Parkin
A
A
Rossello
A
A
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D011756:Diphosphates / Q000737:chemistry* / Q000494:pharmacology; D006564:Herpesviridae / Q000187:drug effects*; D007065:Idoxuridine / Q000031:analogs & derivatives; D008958:Models, Molecular; D008962:Models, Theoretical; D008968:Molecular Conformation
D000998:Antiviral Agents; D011756:Diphosphates; D007065:Idoxuridine