First synthesis and evaluation of the inhibitory effects of aza analogues of TSAO on HIV-1 replication.
Aza TSAO-T derivatives bearing a dihydroisothiazole dioxide ring instead of an oxathiole dioxide ring at the C-3' position on the sugar moiety were prepared. We have synthesized four families of compounds depending on substitution at both N-3 and N-2' '. Biological evaluation showed that these compounds are HIV-1(III(B))-specific and potent reverse transcriptase inhibitors with EC(50) values between 0.13 and 3.5 microM in cell culture.
Laboratoire des Glucides (FRE 2779), Faculté des Sciences, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens, France.
Albert
A
Nguyen Van Nhien
Cyrille
C
Tomassi
Christophe
C
Len
José Luis
JL
Marco-Contelles
Jan
J
Balzarini
Christophe
C
Pannecouque
Erik
E
De Clercq
Denis
D
Postel
D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D015498:HIV-2 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D014529:Uridine / Q000031:analogs & derivatives; D014779:Virus Replication / Q000187:drug effects*
D001372:Aza Compounds; D018894:Reverse Transcriptase Inhibitors; D013141:Spiro Compounds; D013936:Thymidine; C075132:TSAO-T; D014529:Uridine