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.
Nguyen Van Nhien
Albert
A
Laboratoire des Glucides (FRE 2779), Faculté des Sciences, Université de Picardie Jules Verne, 33 rue Saint Leu, 80039 Amiens, France.
Tomassi
Cyrille
C
Len
Christophe
C
Marco-Contelles
José Luis
JL
Balzarini
Jan
J
Pannecouque
Christophe
C
De Clercq
Erik
E
Postel
Denis
D
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