Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA.
Some novel amidate prodrugs of PMEA and PMPA have been synthesised and tested in vitro for their biological activity. Compound 5 in particular showed greatly enhanced antiviral potency compared with the parent nucleotide analogue. In vitro enzymatic studies and structure-activity relationships indicate that the degradation mechanism of such prodrugs may be the same as that described for the phosphoramidate triesters of nucleotide analogues.
Ballatore
C
C
Welsh School of Pharmacy, Cardiff University, UK.
McGuigan
C
C
De Clercq
E
E
Balzarini
J
J
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology; D004355:Drug Stability; D004950:Esterases / Q000378:metabolism; D006801:Humans; D009711:Nucleotides / Q000494:pharmacology; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology*; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000378:metabolism*; D011355:Prodrugs / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D012190:Retroviridae / Q000187:drug effects*; D013329:Structure-Activity Relationship; D000068698:Tenofovir
D000577:Amides; D000998:Antiviral Agents; D009711:Nucleotides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010756:Phosphoric Acids; D011355:Prodrugs; C053001:adefovir; D000068698:Tenofovir; C011067:phosphoramidic acid; D004950:Esterases; D000225:Adenine; D000409:Alanine