Synthesis of phosphonate 3-phthalidyl esters as prodrugs for potential intracellular delivery of phosphonates.
A new prodrug approach for intracellular delivery of phosphonates was developed via the synthesis of 3-phthalidyl esters of 1-naphthalenemethylphosphonate. This approach is advantageous over the traditional acyloxymethyl phosphonate prodrugs, because these prodrugs do not generate formaldehyde and have improved plasma half-lives.
Dang
Q
Q
Department of Medicinal Chemistry, Metabasis Therapeutics, Inc., San Diego, CA 92121, USA.
Brown
B S
BS
van Poelje
P D
PD
Colby
T J
TJ
Erion
M D
MD
D000818:Animals; D004952:Esters / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D009281:Naphthalenes / Q000737:chemistry; D063065:Organophosphonates / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats
D004952:Esters; D009281:Naphthalenes; D063065:Organophosphonates; D011355:Prodrugs; C031721:naphthalene