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.
BIOISOSTERS OF THE DIPHOSPHATE GROUP IN ACTIVATED FORMS OF ANTIHERPES VIRUS AGENTS - A THEORETICAL-STUDY
MACCHIA, MARCO;MARTINELLI, ADRIANO;ROSSELLO, ARMANDO
1994-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
