Design of new mononucleotide prodrugs: aryl (SATE) phosphotriester derivatives.
Synthesis, biological activities and decomposition kinetics of novel phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-tButyl-2-thioethyl (tBuSATE) group and L-tyrosinyl residues are reported. All the derivatives appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments. The proposed decomposition process of these mixed phosphotriesters may involve successively an esterase and then a phosphodiesterase activation.
Peyrottes
S
S
UMR 5625 CNRS-UM II, Université Montpellier II, cc 008, place E. Bataillon, 34095 Montpellier, France.
Schlienger
N
N
Beltran
T
T
Lefebvre
I
I
Pompon
A
A
Gosselin
G
G
Aubertin
A M
AM
Imbach
J L
JL
Périgaud
C
C
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D015195:Drug Design; D004355:Drug Stability; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D019380:Anti-HIV Agents; D004952:Esters; D011355:Prodrugs; D015215:Zidovudine