Potential of 4′-C-substituted nucleosides for the treatment of HIV-1

Hiroyuki Hayakawa, Satoru Kohgo, Kenji Kitano, Noriyuki Ashida, Eiichi Kodama, Hiroaki Mitsuya, Hiroshi Ohrui

Research output: Contribution to journalReview articlepeer-review

50 Citations (Scopus)


Extensive efforts have been made to identify nucleoside reverse transcriptase inhibitors (NRTIs). Eight NRTIs have now been approved for clinical use; however, variants of HIV-1 resistant to these antiviral agents have emerged in patients even when they are treated with combinations [highly active antiretroviral therapy (HAART)]. Thus, the development of novel compounds that are active against drug-resistant HIV-1 variants and that prevent or delay the emergence of resistant HIV-1 variants is urgently needed. Previously, 4′-C-substituted nucleosides (4′-SNs) were designed as new types of NRTIs. They were synthesized and examined as potential therapeutic agents against HIV infection. Among them, several 4′-substituted-2′- deoxynucleosides (4′-SdNs), especially those that bear an ethynyl group, were shown to be active against various laboratory and clinical HIV-1 strains including known drug-resistant variants. These results were recently reported by our collaborators. In this review, we summarize the design, synthesis and demonstrations of the anti-HIV activity of 4′-SNs, and then consider 4′-SNs as potential therapeutic agents for HIV-1.

Original languageEnglish
Pages (from-to)169-187
Number of pages19
JournalAntiviral Chemistry and Chemotherapy
Issue number4
Publication statusPublished - 2004 Jul


  • 4′-SNs
  • Anti-HIV-1 agents
  • Drug-resistant HIV-1 variants
  • NRTIs


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