Design, enantiopure synthesis, and biological evaluation of novel iso-D-2',3'-dideoxy-3'-fluorothianucleoside derivatives as a bioisostere of lamivudine.
Novel iso D-2',3'-dideoxythianucleoside derivatives 1-3 were designed and asymmetrically synthesized to search for new anti-HIV agents. Final compounds 1-3 were evaluated against a variety of viruses including HIV-1 and 2. Only cytosine analog 3 showed a potent anti-VSV activity (EC(50) = 9.43 microg/mL). This result implies that iso 2',3'-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.
College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Korea.
Kyung Ran
KR
Kim
Ah-Young
AY
Park
Hyung Ryong
HR
Moon
Moon Woo
MW
Chun
Lak Shin
LS
Jeong
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D019259:Lamivudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013237:Stereoisomerism; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D019259:Lamivudine