Synthesis and in vitro activity of D- and L-enantiomers of 5-(trifluoromethyl)uracil nucleoside derivatives.
Recently, beta-L-nucleoside analogues have emerged as a new class of sugar modified nucleosides with potential antiviral and/or antitumoral activity. As a part of our ongoing research on this topic, we decided to synthesize 5-CF3-beta-L-dUrd (7), the hitherto unknown L-enantiomer of Trifluridine, an antiherpetic drug approved by FDA but only used in topical applications due to concomitant cytotoxicity. 5-CF3-beta-L-dUrd (7) as well as some other related L-nucleoside derivatives were stereospecifically prepared and tested in vitro against viral (HSV-1 and HSV-2) and human thymidine kinases (TK).
Salvetti
R
R
Università di Pavia, V. Taramelli 12, 27100 Pavia, Italy.
Pregnolato
M
M
Verri
A
A
Focher
F
F
Spadari
S
S
Marchand
A
A
Mathé
C
C
Gosselin
G
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000201:enzymology; D018258:Herpesvirus 2, Human / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D011742:Pyrimidine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D011742:Pyrimidine Nucleotides; D011743:Pyrimidines; C401928:trifluoromethyluracil; D013937:Thymidine Kinase