title: Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA.
abstract: 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.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, UK.
authors.forename: C
authors.initials: C
authors.lastname: Ballatore
authors.forename: C
authors.initials: C
authors.lastname: McGuigan
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
mesh_terms: 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
chemical_list: 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