New insights regarding the potential of the pronucleotide approach in antiviral chemotherapy.
The rationale for a pronucleotide approach based on the use of phosphotriesters which incorporate enzyme-mediated bio-labile protection is discussed in detail. Among the studied bio-labile phosphate protecting groups, the S-acyl-2-thioethyl (SATE) groups appeared the most promising as exemplified in cell culture systems in the case of the pronucleotides of 3'-azido-3'-deoxythymidine, 2',3'-didehydro-3'-deoxythymidine, 2',3'-dideoxyadenosine and acyclovir In vivo implementations of such bis(SATE) pronucleotides have been planned for future animal studies.
Gosselin
G
G
Laboratoire de Chimie Bioorganique, URA CNRS 488, Université de Montpellier II, France.
Girardet
J L
JL
Périgaud
C
C
Benzaria
S
S
Lefebvre
I
I
Schlienger
N
N
Pompon
A
A
Imbach
J L
JL
D000212:Acyclovir / Q000031:analogs & derivatives; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007202:Indicators and Reagents; D008954:Models, Biological; D009711:Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D015215:Zidovudine / Q000031:analogs & derivatives
D000998:Antiviral Agents; D007202:Indicators and Reagents; D009711:Nucleotides; D011355:Prodrugs; D015215:Zidovudine; D000212:Acyclovir