Fluorinated sugar analogues of potential anti-HIV-1 nucleosides.
In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3' -difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-methylcytosine analogue 21, 3'-deoxy-2',3'-didehydro-2' -fluorothymidine (25), 3'-azido-2',3'-dideoxy-2'-fluoro-5-methyluridine (29), 2'-azido-3'-fluoro-2',3'-dideoxy-5-methyluridine (31), and 2'3'-dideoxy-2' -fluoro-5-methyluridine (37). These new nucleosides were screened for their activity against HIV and feline TLV in vitro. None of the compounds showed significant activity. It is interesting to note that such a small modification in the sugar moiety of active anti-HIV nucleosides (i.e., displacement of hydrogen by fluorine) almost completely inactivate the agents.
Huang
J T
JT
Sloan-Kettering Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division of Graduate School of Medical Sciences, Cornell University, New York, New York 10021.
Chen
L C
LC
Wang
L B
LB
Kim
M H
MH
Warshaw
J A
JA
Armstrong
D
D
Zhu
Q Y
QY
Chou
T C
TC
Watanabe
K A
KA
Matulic-Adamic
J
J
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008907:Mink; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D015224:Dideoxynucleosides